Abstract Background: Chai-Ling decoction (CLD), derived from a modification of Xiao-Chai-Hu (XCH) decoction and Wu-Ling-San (WLS) decoction, has been used to treat the early-stage of coronavirus disease 2019 (COVID-19). However, the mechanisms of CLD in COVID-19 remain unknown. In this study, the potential mechanisms of CLD in COVID-19 were preliminarily investigated based on network pharmacology and molecular docking method. Methods: Initially, the active components and targets of CLD were screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper database. The targets of COVID-19 were obtained from GeneCards database. The protein-protein interaction network was established using STRING database to analyze the key targets. Gene Oncology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes analysis were also conducted to evaluate the pathways related to the targets of CLD on COVID-19. Moreover, the compound-target-pathway network was established using Cytoscape 3.2.7. Subsequently, the molecular docking method was performed to select the active compounds with high binding affinity on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2), which is the key target of SARS-CoV-2 in entering target cells. The possible binding sites were also visualized by a three-dimensional graph. Results: Network pharmacology analysis showed that there were 106 active components and 160 targets of CLD. Additionally, 251 targets related to COVID-19 were identified, and 24 candidates of CLD on COVID-19 were selected. A total of 283 GO terms of CLD on COVID-19 were identified, and 181 pathways were screened based on GO and Kyoto Encyclopedia of Genes and Genomes analyses. CLD might alleviate the inflammatory response and improve lung injury to treat COVID-19 through interleukin 17 signaling, T helper cell 17 differentiation, tumor necrosis factor signaling, and hypoxia inducible factor-1 signaling. Besides, molecular docking indicated that beta-sitosterol, kaempferol, and stigmasterol were the top three candidates in CLD with the highest affinity to SARS-CoV-2 and ACE2. Conclusion: Our study identifies the potential mechanisms of CLD on COVID-19 and beta-sitosterol, kaempferol, and stigmasterol may be the key compounds that exert antiviral effects against SARS-CoV-2.
This document discusses cytokine storm syndrome in patients with COVID-19. It defines cytokine storm as an uncontrolled release of inflammatory cytokines that can lead to organ damage. COVID-19 is proposed to progress through four stages, with stage II involving an excessive immune response and cytokine release. Cytokine storm is associated with acute respiratory distress syndrome and multi-organ failure in COVID-19 patients. The document outlines treatments for cytokine storm including immunomodulators, anticoagulants, antivirals, and extracorporeal therapies.
Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus.
Most people who fall sick with COVID-19 will experience mild to moderate symptoms and recover without special treatment.
Perspective of Cardiac Troponin and Membrane Potential in People Living with ...asclepiuspdfs
Background: Hypertension is an event in which the force of the blood against the artery walls is too high leading to severe health complications and increases the risk of heart disease, stroke, and sometimes death. Aim: This study was carried out to determine the levels of cardiac troponin 1 and membrane potential in hypertensive subjects in Owerri, Imo state. Materials and Methods: A total of 120 subjects within the age 30–70 years were recruited for this study. The study consists of 60 subjects who were diagnosed of hypertension and 60 were apparently healthy individuals who served as controls subjects of the same age bracket. The levels of cardiac troponin 1 and membrane potential were analyzed using enzyme-linked immunosorbent assay technique. Data were assessed using SPSS version 20, the mean value with P ˂ 0.05 was considered statistically significant. Results: The result revealed that the levels of cardiac troponin 1 in hypertension were significantly increased when compared with control subjects while the levels of membrane potential were significantly decreased when compared to control at P < 0.05. Conclusion: The increased serum level of cardiac troponin 1 and decreased membrane potential in hypertensive subjects may contribute some risk factors in patients with hypertension.
The document discusses various topics related to sepsis including:
1) Definitions of terms like SIRS, sepsis, septic shock, and their associated signs and symptoms.
2) The inflammatory cascades that occur in response to infection and lead to organ dysfunction.
3) How sepsis affects different organs in the body like the brain, heart, lungs, kidneys, and liver.
4) Two theories for the origin of sepsis - the gut origin theory and lung origin theory.
5) The role of activated protein C in reducing thrombin production and inflammation.
Evaluation of Cardiac Complications in Pateint Undergoing COVID 19 Treatment:...DrHeena tiwari
This study evaluated cardiac complications in 45 COVID-19 patients admitted to the intensive care unit. Electrocardiography and Holter monitoring found various arrhythmias in patients, with atrial fibrillation, premature ventricular contraction, and tachycardia being most common. The mortality rate of arrhythmias in COVID-19 patients was 17.77%. Although arrhythmias are not very frequent in COVID-19, they can be fatal and have a high mortality rate. Early detection of arrhythmias can help prevent deaths.
Role of Corticosteroid in the Management of Covid 19pharmacypawan
This pandemic has given us so many opportunities to rethink the ideas for use of corticosteroids . one of the major help that has been achieved through the corticosteroid is the increase the efficiency of treatment.
1) The study investigated the relationship between body temperature (Tb) abnormalities and disease severity and outcomes in 624 patients with severe sepsis.
2) Patients with hypothermia (Tb ≤36.5°C) had significantly higher organ failure scores, illness severity scores, rates of disseminated intravascular coagulation, and 28-day and hospital mortality compared to patients without hypothermia (Tb >36.5°C).
3) Hypothermia was found to be an independent predictor of increased 28-day mortality in patients with severe sepsis, irrespective of whether they had septic shock.
1) Diabetes is identified as a risk factor for worse outcomes from COVID-19 based on studies from China. Mortality was 10% in COVID-19 patients with diabetes versus 2.5% for non-diabetic patients.
2) People with diabetes have an increased risk of severe COVID-19 infection due to defects in innate immunity from hyperglycemia and an increased inflammatory response.
3) The interaction between the SARS-CoV-2 virus and the renin-angiotensin-aldosterone system, which regulates blood pressure and fluid balance, may help explain the link between diabetes, hypertension, and increased COVID-19 severity. The virus relies on binding to ACE2 receptors to infect
This document discusses cytokine storm syndrome in patients with COVID-19. It defines cytokine storm as an uncontrolled release of inflammatory cytokines that can lead to organ damage. COVID-19 is proposed to progress through four stages, with stage II involving an excessive immune response and cytokine release. Cytokine storm is associated with acute respiratory distress syndrome and multi-organ failure in COVID-19 patients. The document outlines treatments for cytokine storm including immunomodulators, anticoagulants, antivirals, and extracorporeal therapies.
Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus.
Most people who fall sick with COVID-19 will experience mild to moderate symptoms and recover without special treatment.
Perspective of Cardiac Troponin and Membrane Potential in People Living with ...asclepiuspdfs
Background: Hypertension is an event in which the force of the blood against the artery walls is too high leading to severe health complications and increases the risk of heart disease, stroke, and sometimes death. Aim: This study was carried out to determine the levels of cardiac troponin 1 and membrane potential in hypertensive subjects in Owerri, Imo state. Materials and Methods: A total of 120 subjects within the age 30–70 years were recruited for this study. The study consists of 60 subjects who were diagnosed of hypertension and 60 were apparently healthy individuals who served as controls subjects of the same age bracket. The levels of cardiac troponin 1 and membrane potential were analyzed using enzyme-linked immunosorbent assay technique. Data were assessed using SPSS version 20, the mean value with P ˂ 0.05 was considered statistically significant. Results: The result revealed that the levels of cardiac troponin 1 in hypertension were significantly increased when compared with control subjects while the levels of membrane potential were significantly decreased when compared to control at P < 0.05. Conclusion: The increased serum level of cardiac troponin 1 and decreased membrane potential in hypertensive subjects may contribute some risk factors in patients with hypertension.
The document discusses various topics related to sepsis including:
1) Definitions of terms like SIRS, sepsis, septic shock, and their associated signs and symptoms.
2) The inflammatory cascades that occur in response to infection and lead to organ dysfunction.
3) How sepsis affects different organs in the body like the brain, heart, lungs, kidneys, and liver.
4) Two theories for the origin of sepsis - the gut origin theory and lung origin theory.
5) The role of activated protein C in reducing thrombin production and inflammation.
Evaluation of Cardiac Complications in Pateint Undergoing COVID 19 Treatment:...DrHeena tiwari
This study evaluated cardiac complications in 45 COVID-19 patients admitted to the intensive care unit. Electrocardiography and Holter monitoring found various arrhythmias in patients, with atrial fibrillation, premature ventricular contraction, and tachycardia being most common. The mortality rate of arrhythmias in COVID-19 patients was 17.77%. Although arrhythmias are not very frequent in COVID-19, they can be fatal and have a high mortality rate. Early detection of arrhythmias can help prevent deaths.
Role of Corticosteroid in the Management of Covid 19pharmacypawan
This pandemic has given us so many opportunities to rethink the ideas for use of corticosteroids . one of the major help that has been achieved through the corticosteroid is the increase the efficiency of treatment.
1) The study investigated the relationship between body temperature (Tb) abnormalities and disease severity and outcomes in 624 patients with severe sepsis.
2) Patients with hypothermia (Tb ≤36.5°C) had significantly higher organ failure scores, illness severity scores, rates of disseminated intravascular coagulation, and 28-day and hospital mortality compared to patients without hypothermia (Tb >36.5°C).
3) Hypothermia was found to be an independent predictor of increased 28-day mortality in patients with severe sepsis, irrespective of whether they had septic shock.
1) Diabetes is identified as a risk factor for worse outcomes from COVID-19 based on studies from China. Mortality was 10% in COVID-19 patients with diabetes versus 2.5% for non-diabetic patients.
2) People with diabetes have an increased risk of severe COVID-19 infection due to defects in innate immunity from hyperglycemia and an increased inflammatory response.
3) The interaction between the SARS-CoV-2 virus and the renin-angiotensin-aldosterone system, which regulates blood pressure and fluid balance, may help explain the link between diabetes, hypertension, and increased COVID-19 severity. The virus relies on binding to ACE2 receptors to infect
Antibiotics for Acute Exacerbztions of COPD Ashraf ElAdawy
This document discusses the appropriate use of antibiotics in acute exacerbations of chronic obstructive pulmonary disease (COPD). It states that while steroids and bronchodilators are well-established treatments for exacerbations, there is ongoing debate around antibiotic use. Antibiotics are recommended for moderate to severe exacerbations with increased cough and sputum purulence as this indicates likely bacterial infection. Sputum culture alone should not determine antibiotic use, and severity factors like purulence, underlying lung function, age and comorbidities should guide treatment decisions. Antibiotics may reduce mortality and treatment failure when targeted at patients with bacterial exacerbations.
1) Community-acquired pneumonia (CAP) has significant short- and long-term impacts on public health through morbidity and mortality. While antibiotics have reduced initial mortality, mortality remains stable or has increased since 1950. Survivors often experience new cognitive and functional impairments.
2) Irrespective of the infecting pathogen, the host's inability to fully downregulate systemic inflammation contributes to acute and long-term morbidity and mortality from CAP. Glucocorticoids are natural regulators of inflammation and their levels increase during infection.
3) Evidence shows prolonged low-dose glucocorticoid treatment in patients with severe CAP, sepsis, and acute respiratory distress syndrome downregulates systemic inflammation and improves cardiovascular and
This document provides guidelines for the diagnosis and treatment of community-acquired pneumonia (CAP) in adults. It addresses 12 questions regarding best practices for diagnosis and management of CAP in both outpatient and inpatient settings. For each question, the document reviews the relevant evidence and provides treatment recommendations based on that evidence. The recommendations aim to optimize patient outcomes while minimizing unnecessary testing and promoting judicious antibiotic use.
Systemic inflammatory response syndrome (SIRS) is a clinical syndrome characterized by a dysregulated inflammatory response that can be caused by infectious or noninfectious processes. Sepsis is defined as SIRS caused by a confirmed or suspected infection. As sepsis progresses it can lead to severe sepsis, septic shock, and multiple organ dysfunction syndrome (MODS). Key aspects of managing sepsis include early identification of infection, administering antibiotics, and supporting vital organ function by correcting hypoxemia, hypotension, and hypoperfusion. Investigations should identify the source of infection and assess organ dysfunction, while priorities of treatment are stabilizing respiration and circulation followed by identifying and treating the underlying infection.
This document provides definitions and guidelines for the management of septic shock. It begins with definitions of terms like SIRS, sepsis, septic shock, and qSOFA. It then discusses the pathophysiology of sepsis, including the host immune response and organ dysfunction. Manifestations across organ systems are outlined. Recommended markers for sepsis diagnosis are described. Treatment protocols emphasize early fluid resuscitation, screening programs, appropriate cultures before antibiotics, initiating broad-spectrum antibiotics within 1 hour, and optimizing antibiotic dosing and duration. Combination empiric therapy for septic shock may be considered but should be de-escalated once infection is controlled.
Criterios diagnostivcos de sespsi en quemadposAlfredo Garcia
The document discusses criteria for diagnosing sepsis in burn patients. It states that sepsis with multiple organ dysfunction is a major cause of death for burn patients. Specific criteria have been proposed for diagnosing sepsis in burn patients, as the general criteria do not always apply due to the physiological effects of burns. The American Burn Association criteria for diagnosing sepsis in burn patients requires an infection be present along with three of seven specified criteria, such as fever, tachycardia, thrombocytopenia, or inability to continue enteral feedings. Distinguishing sepsis from the normal post-burn inflammatory response can be difficult.
Septicemia international management guidelineNeurologyKota
This document provides guidelines for the management of sepsis and septic shock. It defines key terms like sepsis, severe sepsis, septic shock, and systemic inflammatory response syndrome. It outlines variables for diagnosis and assessing organ dysfunction. It recommends initial resuscitation goals within 3-6 hours including measuring lactate, administering antibiotics and fluids, and applying vasopressors if needed. It provides guidelines for diagnosis, source control, antibiotic therapy, fluid therapy, vasopressor use, and other supportive treatments. Recommendations are evidence-based with assigned grade levels.
Renin angiotensin system inhibitors improve the clinical outcomes of covid 19...gisa_legal
This study evaluated the effects of renin-angiotensin system (RAS) inhibitors on COVID-19 patients with hypertension. The study found that:
1) Patients receiving ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) had lower rates of severe disease and lower levels of the inflammatory marker IL-6 compared to those receiving other hypertension drugs.
2) ACEI/ARB therapy was associated with higher CD3 and CD8 T cell counts and lower peak viral loads.
3) The results suggest that continuing or prioritizing ACEIs/ARBs for hypertension treatment may improve clinical outcomes for COVID-19 patients with hypertension by reducing inflammation and modulating
Serum Procalcitonin as a marker of infection in chronic kidney disease patien...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
The document discusses anticoagulation in COVID-19 patients. It notes that COVID-19 infection can cause a cytokine storm and increased risk of thrombosis. Studies have shown that 1/3 of hospitalized COVID-19 patients develop thrombotic complications. Several guidelines recommend prophylactic anticoagulation for hospitalized COVID-19 patients to reduce the risk of thromboembolism and lower mortality. Early initiation of prophylactic anticoagulation is associated with a 27% reduced risk of death within 30 days. The document discusses diagnostic tests for coagulopathy in COVID-19 patients and potential radiological findings of thromboembolic complications.
HELICOBACTER PYLORI and CORONARY ARTERY DISEASEhungnguyenthien
This document discusses the relationship between Helicobacter pylori infection and coronary artery disease. It begins with a review of infectious and non-infectious triggers of atherosclerosis. It then examines studies showing a relationship between H. pylori infection, especially strains expressing CagA, and markers of inflammation associated with increased risk of coronary artery disease. The document explores potential pathogenic mechanisms such as inflammatory responses, lipid modification, molecular mimicry of heat shock proteins, and hyperhomocysteinemia. It also notes findings of H. pylori DNA in atherosclerotic plaques and recommends treatment regimens to eradicate H. pylori infection.
This document discusses the management of sepsis and septic shock. It defines sepsis as a life-threatening organ dysfunction caused by infection and an acute change in the SOFA score of greater than 2 points due to infection. Septic shock is a subset of sepsis with circulatory and metabolic abnormalities increasing the risk of mortality. The management of sepsis involves early fluid resuscitation, administration of broad-spectrum antibiotics within 1 hour, and vasopressors for hypotension unresponsive to fluids.
The document discusses the case of a 51-year-old man presenting with severe sepsis and septic shock. It outlines his initial treatment including IV fluids, antibiotics, and vasopressors. Further workup revealed a hepatic abscess which was drained surgically. The patient eventually recovered after 10 days of targeted antibiotic therapy guided by cultures. The document also reviews key literature on defining sepsis, early management principles like early goal-directed therapy, and optimization of oxygen delivery through fluid resuscitation, vasopressors, inotropes, and blood transfusions.
1. The document discusses SARS-CoV-2, the virus that causes COVID-19, including its transmission, clinical manifestations, risk factors, investigations, and management guidelines.
2. Key points include that SARS-CoV-2 is transmitted via droplets or contact and may cause asymptomatic to critical illness. Common symptoms include fever, cough and shortness of breath.
3. Older adults and those with pre-existing medical conditions are at higher risk for severe illness. Diagnosis is confirmed via RT-PCR testing of respiratory samples, while chest imaging may show pneumonia.
Covid 19 and the cardiovascular system implications for risk assessment dia...Ramachandra Barik
The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and
mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial
pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the
cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is
increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.
The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular
fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant
myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically,
SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane
angiotensin-converting enzyme 2 (ACE2) —a homologue of ACE—to enter type 2 pneumocytes, macrophages,
perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.
Hence, patients should not discontinue their use. Moreover, renin–angiotensin–aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm
[interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and
continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization
may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures
1) The document defines sepsis, severe sepsis, and septic shock and provides diagnostic criteria. It discusses initial resuscitation goals for the first 6 hours including fluid administration, vasopressors, and ScvO2/lactate monitoring.
2) Management recommendations are provided for antimicrobial therapy, source control, fluid therapy, vasopressors, blood products, glucose control, and other areas. Bundle elements are outlined to be completed within 3 and 6 hours of diagnosis.
3) Guidelines include level of evidence ratings and discuss evidence from studies on topics like fluid resuscitation, vasopressor use, and ventilator management for patients with severe sepsis or septic shock.
This document outlines hypersensitivity pneumonitis (HP), beginning with its historical perspective of being first described in farmers exposed to moldy grains in the early 1900s. It then discusses the epidemiology, finding HP prevalence is less than 2% and most common causes are exposure to avian proteins. The pathogenesis involves an abnormal immune response to inhaled antigens like organic materials from birds or fungi. Clinical findings are described for acute, subacute and chronic HP, with acute presenting with flu-like symptoms and subacute/chronic showing interstitial lung disease on imaging and pulmonary function tests.
Latest definition of sepsis, application of qSOFA, latest evidence on treatment of septic shock,role of fluids, role of steroids, isobalance salt solution
Molecular mechanism prediction analysis of compound Kushen injection in the t...LucyPi1
Abstract Background: As one of the eight effective traditional Chinese medicines for the treatment of atypical pneumonia, compound Kushen injection (CKI) played an important role in combating pneumonia caused by severe acute respiratory syndrome coronavirus 2 virus in China in 2003. CKI is known to inhibit inflammation, and its main chemical components, namely matrine and oxymatrine, can promote Th cells to recognize and eliminate viruses. In this study, network pharmacology and molecular docking were used to explore the mechanisms of CKI for treating coronavirus disease 2019. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and other related literature were used to screen CKI’s active ingredients in the blood. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Swiss Target Prediction and STITCH were used to search for potential targets of the active ingredients. The “ingredient-target” network was constructed using the Cytoscape software. The STRING online database was used to construct a target protein-protein interaction network that can be visualized and analyzed using the Cytoscape software to obtain key targets. Results: Sophocarpine, sophoridine, matrine, (+)-allomatrine, AIDS211310, and sophranol were the six active ingredients. After docking the active ingredients with severe acute respiratory syndrome coronavirus 2 3CL hydrolase and angiotensin-converting enzyme 2 (ACE2), they displayed suitable affinity, which could block viral replication and its binding to ACE2. The key targets mainly involved inflammatory factors, such as interleukin-6 (IL-6) and tumor necrosis factor (TNF). Gene Ontology enrichment analysis mainly indicated the IL-6 cytokine-mediated signaling pathway and cytokine-mediated signaling pathway. The Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis mainly indicated steroid hormone biosynthesis and the TNF signaling pathway. Conclusion: The alkaloids in CKI can block viral replication and its binding to severe acute respiratory syndrome coronavirus 2 and ACE2 receptors. They regulate the IL-6-mediated signaling pathway, TNF signaling pathway, and steroid hormone biosynthesis, thereby initiating therapeutic responses against coronavirus disease 2019.
Can Yin-Chai-Xiao-Du decoction be useful of COVID-19? the mechanism research ...LucyPi1
Abstract Background: In this study, we preliminarily investigated the mechanism of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 by the method of network pharmacology. Methods: The potential targets and pathways of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 were examined using network pharmacology; the ingredient and active targets of Yin-Chai-Xiao-Du decoction were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper databases; the COVID-19-related targets were obtained from the online Mendelian inheritance in man, GeneCards, and GeneMANIA databases; the STRING database and Cytoscape were used to build a protein-protein interaction network, and a Network Analyzer tool was used to perform topology analysis to screen for the key ingredients and targets; the ClueGO and KOBAS 3.0 databases were for the enrichment analysis of gene function (Gene Oncology) and gene pathway (Kyoto Encyclopedia of Genes and Genomes); the herb-ingredient-target-pathway network diagram was constructed by Cytoscape. Results: The core herbs screened by the network pharmacological analysis were Jinyinhua (Lonicerae japonicae flos), Lianqiao (Forsythia suspensa), Chaihu (Bupleuri radix), Huangqin (Scutellariae radix), Yinchen (Herba Artemisiae Scopariae), Guanghuoxiang (Pogostemonis herba), Roudoukou (Semen myristicae) and Qinghao (Artemisiae annuae herba). A total of 293 active ingredients were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the key ingredients were quercetin, kaempferol, isorhamnetin, stigmasterol, beta-sitosterol, and luteolin. Yin-Chai-Xiao-Du decoction has 138 COVID-19-related targets, and the key targets were mitogen-activated protein kinase 3, interleukin-6, tumor necrosis factor, vascular endothelial growth factor A, and CC motif ligand 2. Kyoto Encyclopedia of Genes and Genomes analysis revealed 120 enriched gene pathways, and the key pathways were signaling by interleukins, immune system, cytokine signaling in the immune system, and the signaling pathways of interleukin-17, tumor necrosis factor, and relaxin. Conclusion: The core herbs of Yin-Chai-Xiao-Du decoction are Jinyinhua (Lonicerae japonicae flos), Lianqiao (Forsythia suspensa), Chaihu (Bupleuri radix), Huangqin (Scutellariae radix), Yinchen (Herba Artemisiae Scopariae), Guanghuoxiang (Pogostemonis herba), Roudoukou (Semen myristicae) and Qinghao (Artemisiae annuae herba). The key ingredients are quercetin, kaempferol, isorhamnetin, stigmasterol, and beta-sitosterol; the critical targets are luteolin, interleukin-6, mitogen-activated protein kinase 3, tumor necrosis factor, and CC motif ligand 2; and the core signaling pathways are those mediated by interleukin-17, tumor necrosis factor, and relaxin.
Antibiotics for Acute Exacerbztions of COPD Ashraf ElAdawy
This document discusses the appropriate use of antibiotics in acute exacerbations of chronic obstructive pulmonary disease (COPD). It states that while steroids and bronchodilators are well-established treatments for exacerbations, there is ongoing debate around antibiotic use. Antibiotics are recommended for moderate to severe exacerbations with increased cough and sputum purulence as this indicates likely bacterial infection. Sputum culture alone should not determine antibiotic use, and severity factors like purulence, underlying lung function, age and comorbidities should guide treatment decisions. Antibiotics may reduce mortality and treatment failure when targeted at patients with bacterial exacerbations.
1) Community-acquired pneumonia (CAP) has significant short- and long-term impacts on public health through morbidity and mortality. While antibiotics have reduced initial mortality, mortality remains stable or has increased since 1950. Survivors often experience new cognitive and functional impairments.
2) Irrespective of the infecting pathogen, the host's inability to fully downregulate systemic inflammation contributes to acute and long-term morbidity and mortality from CAP. Glucocorticoids are natural regulators of inflammation and their levels increase during infection.
3) Evidence shows prolonged low-dose glucocorticoid treatment in patients with severe CAP, sepsis, and acute respiratory distress syndrome downregulates systemic inflammation and improves cardiovascular and
This document provides guidelines for the diagnosis and treatment of community-acquired pneumonia (CAP) in adults. It addresses 12 questions regarding best practices for diagnosis and management of CAP in both outpatient and inpatient settings. For each question, the document reviews the relevant evidence and provides treatment recommendations based on that evidence. The recommendations aim to optimize patient outcomes while minimizing unnecessary testing and promoting judicious antibiotic use.
Systemic inflammatory response syndrome (SIRS) is a clinical syndrome characterized by a dysregulated inflammatory response that can be caused by infectious or noninfectious processes. Sepsis is defined as SIRS caused by a confirmed or suspected infection. As sepsis progresses it can lead to severe sepsis, septic shock, and multiple organ dysfunction syndrome (MODS). Key aspects of managing sepsis include early identification of infection, administering antibiotics, and supporting vital organ function by correcting hypoxemia, hypotension, and hypoperfusion. Investigations should identify the source of infection and assess organ dysfunction, while priorities of treatment are stabilizing respiration and circulation followed by identifying and treating the underlying infection.
This document provides definitions and guidelines for the management of septic shock. It begins with definitions of terms like SIRS, sepsis, septic shock, and qSOFA. It then discusses the pathophysiology of sepsis, including the host immune response and organ dysfunction. Manifestations across organ systems are outlined. Recommended markers for sepsis diagnosis are described. Treatment protocols emphasize early fluid resuscitation, screening programs, appropriate cultures before antibiotics, initiating broad-spectrum antibiotics within 1 hour, and optimizing antibiotic dosing and duration. Combination empiric therapy for septic shock may be considered but should be de-escalated once infection is controlled.
Criterios diagnostivcos de sespsi en quemadposAlfredo Garcia
The document discusses criteria for diagnosing sepsis in burn patients. It states that sepsis with multiple organ dysfunction is a major cause of death for burn patients. Specific criteria have been proposed for diagnosing sepsis in burn patients, as the general criteria do not always apply due to the physiological effects of burns. The American Burn Association criteria for diagnosing sepsis in burn patients requires an infection be present along with three of seven specified criteria, such as fever, tachycardia, thrombocytopenia, or inability to continue enteral feedings. Distinguishing sepsis from the normal post-burn inflammatory response can be difficult.
Septicemia international management guidelineNeurologyKota
This document provides guidelines for the management of sepsis and septic shock. It defines key terms like sepsis, severe sepsis, septic shock, and systemic inflammatory response syndrome. It outlines variables for diagnosis and assessing organ dysfunction. It recommends initial resuscitation goals within 3-6 hours including measuring lactate, administering antibiotics and fluids, and applying vasopressors if needed. It provides guidelines for diagnosis, source control, antibiotic therapy, fluid therapy, vasopressor use, and other supportive treatments. Recommendations are evidence-based with assigned grade levels.
Renin angiotensin system inhibitors improve the clinical outcomes of covid 19...gisa_legal
This study evaluated the effects of renin-angiotensin system (RAS) inhibitors on COVID-19 patients with hypertension. The study found that:
1) Patients receiving ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) had lower rates of severe disease and lower levels of the inflammatory marker IL-6 compared to those receiving other hypertension drugs.
2) ACEI/ARB therapy was associated with higher CD3 and CD8 T cell counts and lower peak viral loads.
3) The results suggest that continuing or prioritizing ACEIs/ARBs for hypertension treatment may improve clinical outcomes for COVID-19 patients with hypertension by reducing inflammation and modulating
Serum Procalcitonin as a marker of infection in chronic kidney disease patien...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
The document discusses anticoagulation in COVID-19 patients. It notes that COVID-19 infection can cause a cytokine storm and increased risk of thrombosis. Studies have shown that 1/3 of hospitalized COVID-19 patients develop thrombotic complications. Several guidelines recommend prophylactic anticoagulation for hospitalized COVID-19 patients to reduce the risk of thromboembolism and lower mortality. Early initiation of prophylactic anticoagulation is associated with a 27% reduced risk of death within 30 days. The document discusses diagnostic tests for coagulopathy in COVID-19 patients and potential radiological findings of thromboembolic complications.
HELICOBACTER PYLORI and CORONARY ARTERY DISEASEhungnguyenthien
This document discusses the relationship between Helicobacter pylori infection and coronary artery disease. It begins with a review of infectious and non-infectious triggers of atherosclerosis. It then examines studies showing a relationship between H. pylori infection, especially strains expressing CagA, and markers of inflammation associated with increased risk of coronary artery disease. The document explores potential pathogenic mechanisms such as inflammatory responses, lipid modification, molecular mimicry of heat shock proteins, and hyperhomocysteinemia. It also notes findings of H. pylori DNA in atherosclerotic plaques and recommends treatment regimens to eradicate H. pylori infection.
This document discusses the management of sepsis and septic shock. It defines sepsis as a life-threatening organ dysfunction caused by infection and an acute change in the SOFA score of greater than 2 points due to infection. Septic shock is a subset of sepsis with circulatory and metabolic abnormalities increasing the risk of mortality. The management of sepsis involves early fluid resuscitation, administration of broad-spectrum antibiotics within 1 hour, and vasopressors for hypotension unresponsive to fluids.
The document discusses the case of a 51-year-old man presenting with severe sepsis and septic shock. It outlines his initial treatment including IV fluids, antibiotics, and vasopressors. Further workup revealed a hepatic abscess which was drained surgically. The patient eventually recovered after 10 days of targeted antibiotic therapy guided by cultures. The document also reviews key literature on defining sepsis, early management principles like early goal-directed therapy, and optimization of oxygen delivery through fluid resuscitation, vasopressors, inotropes, and blood transfusions.
1. The document discusses SARS-CoV-2, the virus that causes COVID-19, including its transmission, clinical manifestations, risk factors, investigations, and management guidelines.
2. Key points include that SARS-CoV-2 is transmitted via droplets or contact and may cause asymptomatic to critical illness. Common symptoms include fever, cough and shortness of breath.
3. Older adults and those with pre-existing medical conditions are at higher risk for severe illness. Diagnosis is confirmed via RT-PCR testing of respiratory samples, while chest imaging may show pneumonia.
Covid 19 and the cardiovascular system implications for risk assessment dia...Ramachandra Barik
The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and
mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial
pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the
cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is
increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.
The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular
fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant
myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically,
SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane
angiotensin-converting enzyme 2 (ACE2) —a homologue of ACE—to enter type 2 pneumocytes, macrophages,
perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.
Hence, patients should not discontinue their use. Moreover, renin–angiotensin–aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm
[interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and
continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization
may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures
1) The document defines sepsis, severe sepsis, and septic shock and provides diagnostic criteria. It discusses initial resuscitation goals for the first 6 hours including fluid administration, vasopressors, and ScvO2/lactate monitoring.
2) Management recommendations are provided for antimicrobial therapy, source control, fluid therapy, vasopressors, blood products, glucose control, and other areas. Bundle elements are outlined to be completed within 3 and 6 hours of diagnosis.
3) Guidelines include level of evidence ratings and discuss evidence from studies on topics like fluid resuscitation, vasopressor use, and ventilator management for patients with severe sepsis or septic shock.
This document outlines hypersensitivity pneumonitis (HP), beginning with its historical perspective of being first described in farmers exposed to moldy grains in the early 1900s. It then discusses the epidemiology, finding HP prevalence is less than 2% and most common causes are exposure to avian proteins. The pathogenesis involves an abnormal immune response to inhaled antigens like organic materials from birds or fungi. Clinical findings are described for acute, subacute and chronic HP, with acute presenting with flu-like symptoms and subacute/chronic showing interstitial lung disease on imaging and pulmonary function tests.
Latest definition of sepsis, application of qSOFA, latest evidence on treatment of septic shock,role of fluids, role of steroids, isobalance salt solution
Molecular mechanism prediction analysis of compound Kushen injection in the t...LucyPi1
Abstract Background: As one of the eight effective traditional Chinese medicines for the treatment of atypical pneumonia, compound Kushen injection (CKI) played an important role in combating pneumonia caused by severe acute respiratory syndrome coronavirus 2 virus in China in 2003. CKI is known to inhibit inflammation, and its main chemical components, namely matrine and oxymatrine, can promote Th cells to recognize and eliminate viruses. In this study, network pharmacology and molecular docking were used to explore the mechanisms of CKI for treating coronavirus disease 2019. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and other related literature were used to screen CKI’s active ingredients in the blood. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Swiss Target Prediction and STITCH were used to search for potential targets of the active ingredients. The “ingredient-target” network was constructed using the Cytoscape software. The STRING online database was used to construct a target protein-protein interaction network that can be visualized and analyzed using the Cytoscape software to obtain key targets. Results: Sophocarpine, sophoridine, matrine, (+)-allomatrine, AIDS211310, and sophranol were the six active ingredients. After docking the active ingredients with severe acute respiratory syndrome coronavirus 2 3CL hydrolase and angiotensin-converting enzyme 2 (ACE2), they displayed suitable affinity, which could block viral replication and its binding to ACE2. The key targets mainly involved inflammatory factors, such as interleukin-6 (IL-6) and tumor necrosis factor (TNF). Gene Ontology enrichment analysis mainly indicated the IL-6 cytokine-mediated signaling pathway and cytokine-mediated signaling pathway. The Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis mainly indicated steroid hormone biosynthesis and the TNF signaling pathway. Conclusion: The alkaloids in CKI can block viral replication and its binding to severe acute respiratory syndrome coronavirus 2 and ACE2 receptors. They regulate the IL-6-mediated signaling pathway, TNF signaling pathway, and steroid hormone biosynthesis, thereby initiating therapeutic responses against coronavirus disease 2019.
Can Yin-Chai-Xiao-Du decoction be useful of COVID-19? the mechanism research ...LucyPi1
Abstract Background: In this study, we preliminarily investigated the mechanism of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 by the method of network pharmacology. Methods: The potential targets and pathways of Yin-Chai-Xiao-Du decoction for the treatment of COVID-19 were examined using network pharmacology; the ingredient and active targets of Yin-Chai-Xiao-Du decoction were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper databases; the COVID-19-related targets were obtained from the online Mendelian inheritance in man, GeneCards, and GeneMANIA databases; the STRING database and Cytoscape were used to build a protein-protein interaction network, and a Network Analyzer tool was used to perform topology analysis to screen for the key ingredients and targets; the ClueGO and KOBAS 3.0 databases were for the enrichment analysis of gene function (Gene Oncology) and gene pathway (Kyoto Encyclopedia of Genes and Genomes); the herb-ingredient-target-pathway network diagram was constructed by Cytoscape. Results: The core herbs screened by the network pharmacological analysis were Jinyinhua (Lonicerae japonicae flos), Lianqiao (Forsythia suspensa), Chaihu (Bupleuri radix), Huangqin (Scutellariae radix), Yinchen (Herba Artemisiae Scopariae), Guanghuoxiang (Pogostemonis herba), Roudoukou (Semen myristicae) and Qinghao (Artemisiae annuae herba). A total of 293 active ingredients were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the key ingredients were quercetin, kaempferol, isorhamnetin, stigmasterol, beta-sitosterol, and luteolin. Yin-Chai-Xiao-Du decoction has 138 COVID-19-related targets, and the key targets were mitogen-activated protein kinase 3, interleukin-6, tumor necrosis factor, vascular endothelial growth factor A, and CC motif ligand 2. Kyoto Encyclopedia of Genes and Genomes analysis revealed 120 enriched gene pathways, and the key pathways were signaling by interleukins, immune system, cytokine signaling in the immune system, and the signaling pathways of interleukin-17, tumor necrosis factor, and relaxin. Conclusion: The core herbs of Yin-Chai-Xiao-Du decoction are Jinyinhua (Lonicerae japonicae flos), Lianqiao (Forsythia suspensa), Chaihu (Bupleuri radix), Huangqin (Scutellariae radix), Yinchen (Herba Artemisiae Scopariae), Guanghuoxiang (Pogostemonis herba), Roudoukou (Semen myristicae) and Qinghao (Artemisiae annuae herba). The key ingredients are quercetin, kaempferol, isorhamnetin, stigmasterol, and beta-sitosterol; the critical targets are luteolin, interleukin-6, mitogen-activated protein kinase 3, tumor necrosis factor, and CC motif ligand 2; and the core signaling pathways are those mediated by interleukin-17, tumor necrosis factor, and relaxin.
Efficacy of Xuebijing injection for the treatment of coronavirus disease 2019...LucyPi1
Abstract Background: To evaluate the mechanism of Chinese patent drug Xuebijing (XBJ) injection in the treatment of a new coronavirus disease 2019 (COVID-19) based on network pharmacology and molecular docking technology. Methods: The TCMSP database was employed to collect and screen the active ingredients of the Chinese herb contained in the XBJ injection. The GeneCards database and STRING database were applied to collect and expand the targets of COVID-19 and compare and screen the related targets of COVID-19 by XBJ injection. Cytoscape was employed to build a network connecting Chinese medicine, compounds, targets, disease, and topology analysis was performed via the Network Analyzer to screen the key ingredients and targets. The software of Schrödinger molecular docking was used to verify the binding activity of the key ingredients of XBJ injection and the key targets of COVID-19. Metascape platform and DAVID database were utilized to conduct Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis on the key targets of COVID-19 treated by XBJ injection. Results: Eight key compounds and 15 key targets were screened and verified by molecular docking; these key compounds included luteolin, quercetin, baicalein, and kaempferol. The key targets included DPP4, AR, ESR1, CALM1, and protein kinase 1. Gene Ontology analysis involved an apoptosis and hypoxia reaction and the changes in blood vessel morphology. Kyoto Encyclopedia of Genes and Genomes analysis involved signaling pathways of hypoxia inducible factor-1, VEGF, and PI3K/AKT/NF-κB. Conclusion: The mechanism of XBJ injection when used to treat COVID-19 should be further investigated as the key compounds in XBJ regulated the expression of key targets such as protein kinase 1, VEGF-A, B-cell lymphoma-2, and TNF, which affected the COVID-19 receptors such as angiotensin-converting enzyme 2 and signaling pathways like hypoxia inducible factor-1, PI3K-Akt, and NF-κB, which alleviated the inflammation, respiratory distress, and hypoxia caused by COVID-19 infection.
Traditional Chinese medicine for treatment of coronavirus disease 2019: a reviewLucyPi1
Abstract Since late December in 2019, the coronavirus disease 2019 has received extensive attention for its widespread prevalence. A number of clinical workers and researchers have made great efforts to understand the pathogenesis and clinical characteristics and develop effective drugs for treatment. However, no effective drugs with antiviral effects on severe acute respiratory syndrome coronavirus 2 have been discovered currently. Traditional Chinese medicine (TCM) has gained abundant experience in the treatment of infectious diseases for thousands of years. In this review, the authors summarized the clinical outcome, pathogensis and current application of TCM on coronavirus disease 2019. Further, we discussed the potential mechanisms and the future research directions of TCM against severe acute respiratory syndrome coronavirus 2.
The document describes a study on the effectiveness of tocilizumab in treating severe COVID-19 patients. 20 severe or critical COVID-19 patients were given tocilizumab in addition to routine therapy. Within days of treatment, patients saw improved symptoms, reduced oxygen needs, and absorption of lung lesions on CT scans. Inflammatory markers decreased and 19 of the 20 patients were discharged within about two weeks. The study provides evidence that tocilizumab is an effective treatment for severe COVID-19 patients by reducing the cytokine storm.
Dissecting the underlying pharmaceutical mechanism of Danggui Buxue decoction...LucyPi1
Abstract Backgroud: Danggui Buxue decoction (DBD), a classical prescription in traditional Chinese medicine, has been found to have protective effect on bleomycin-induced pulmonary fibrosis in rats by reducing alveolar inflammation and fibrosis. However, the biological activity of individual chemical components and mechanism of action of whole formula are not clear. Methods: Potential targets of active ingredients of DBD were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SymMap database. Target genes related to idiopathic pulmonary fibrosis were obtained from the Online Mendelian Inheritance in Man database, Therapeutic Targets Database and Gkb database. Then, the common targets were obtained by overlapping the potential targets of active ingredients in DBD and diseases related targets. The selected targets were subjected to Kyoto Encyclopedia of Genes and Genomes signaling pathway and Gene Ontology analysis, and the network map of active component-target-pathway was established using Cytoscape 3.7.1 software. The active components of DBD with most targets were selected for fibrosis-related marker verification. The mRNA and protein expression of fibrosis markers, α-smooth muscle actin, collagen 1 and fibronectin, were detected in TGF-β1-induced fibroblast cell line after treatment with the active components. Results: The 14 active ingredients, such as quercetin and kaempferol, were screened from DBD. It acts on 26 targets like estrogen receptor 2 and prostaglandin-endoperoxide synthase 2, and mainly involves 38 signaling pathways such as cell inflammation and autophagy. Kaempferol and quercetin are the two compounds with the highest network regulation, which can inhibit the transformation of fibroblasts into myofibroblasts and reduce the expression of fibrosis markers α-smooth muscle actin, collagen 1 and fibronectin. Conclusion: The integration mode of multi-component, multi-target, multi-channel and mechanism of DBD in the treatment of idiopathic pulmonary fibrosis are predicted by means of network pharmacology. Our study could indicate the direction of further anti-fibrotic mechanism research.
Chlorogenic acid may be a potent inhibitor of dimeric SARS-CoV-2 main proteas...LucyPi1
Abstract Background: Since the emergence of coronavirus disease 2019 to date, there is no available approved drug or definitive treatment for coronavirus disease 2019 viral infection, and the identification of novel hits against therapeutic targets has become a global emergency. Echinacea purpurea is a traditional herb utilized to treat cough, fever, sore throat, respiratory tract infection, and so on as an immune stimulant. In this study, in silico molecular docking approach was used to screen phytocompounds from E. purpurea against severe acute respiratory syndrome coronavirus 2 main protease 3C-like protease (3CLpro) and severe acute respiratory syndrome coronavirus main peptidase (96% sequence similarity) to blunt the viral gene expression and viral replication. Methods: Initially, we screened phytocompounds for their druggability and ADMET property. Furthermore, x-ray crystallographic structures of main proteases 3CLpro and main peptidase having Protein Data Bank ID 6LU7 and 2GTB were used as protein targets for the identification of potential drug candidates. We performed docking using AutoDock Vina by PyRx 0.8 software. BIOVIA Discovery Studio Visualizer v2019 was used to analyze ligand-protein complex. The probable protein targets of the selected compound were predicted by BindingDB (P ≥ 0.7). STRING and Kyoto Encyclopedia of Genes and Genomes pathways are utilized to identify the molecular pathways modulated by the predicted targets (FDR ≤ 0.05), and the network interaction between compounds and protein pathways was constricted by Cytoscape 3.6.1. Results: Among all the compounds, chlorogenic acid showed druggable characteristics and scored the lowest binding energy with main protease and main peptidase via interacting with active site 1 domain amino acid residues. Interestingly, chlorogenic acid interacted with Phe140 main protease 3CLpro, which is potentially involved in the dimerization. Enrichment analysis identified chlorogenic acid to modulate insulin resistance, necroptosis, interleukin-17, tumor necrosis factor signaling pathway, legionellosis, T helper 17 cell differentiation, advanced glycation end products and receptor for advanced glycation end products, mitogen-activated protein kinase, Ras, estrogen, vascular endothelial growth factor, B-cell receptor, nuclear factor kappa B, Rap1, hypoxia inducible factor-1, phosphatidylinositide 3-kinase-Akt, insulin, mechanistic target of rapamycin, p53, retinoic acid inducible gene I like receptor, and ErbB signaling pathways. Conclusion: Chlorogenic acid may act as a potent main protease 3CLpro inhibitor and may also inhibit the severe acute respiratory syndrome coronavirus 2 dimerization, viral gene expression, and replication within the lung epithelium. Chlorogenic acid may go a long way in finding one of the multipronged solutions to tackle coronavirus disease 2019 viral infection in the future.
Major reduction of NKT cells in patients with severe COVID-19 pneumoniaMHosseini6
This document summarizes a study examining immune cell subsets in patients with COVID-19 pneumonia. Peripheral blood samples were obtained from 45 COVID-19 patients and 19 healthy donors. Using flow cytometry, the study characterized T cells, NK cells, and NKT cells. COVID-19 patients had higher percentages of mature NK cells and lower percentages of NKT and less mature NK cells compared to healthy donors. Severe COVID-19 patients had significantly lower NKT cell percentages. Lower NKT cell percentages were independently associated with more severe disease. The findings suggest NKT cells may play a role in the pathogenesis of COVID-19.
Treatment of COVID-19; old tricks for new challengesLuisaSarlat
Coronavirus disease (COVID-19), which appeared in December 2019, presents a global challenge, particularly in the rapid increase of critically ill patients with pneumonia and absence of definitive treatment. To date, over 81,000 cases have been confirmed, with over 2700 deaths. The mortality appears to be around 2%; early published data indicate 25.9% with SARS-CoV-2 pneumonia required ICU admission and 20.1% developed acute respiratory distress syndrome
A broad perspective on COVID-19: a global pandemic and a focus on preventive ...LucyPi1
Abstract Coronavirus 2019 has become a highly infectious disease caused by severe acute respiratory syndrome coronavirus-2, a strain of novel coronavirus, which challenges millions of global healthcare facilities. Coronavirus are sub-microscopic, single stranded positive sense RNA viruses that leads to multi organ dysfunction syndrome, severe acute and chronic respiratory distress syndrome and pneumonia. The spike glycoprotein structure of the virus causes the viral protein to bind with the receptors on the lung and gut through angiotensin-converting enzyme 2. In some cases, the infected patients become hyper to the immune system because of the uncontrolled production of cytokines resulting in “cytokine storm”, a devastating consequence of coronavirus disease 2019. Due to the rapid mutant strain and infective nature of severe acute respiratory syndrome coronavirus-2, discovering a drug or developing a vaccine remains a global challenge. However, some anti-viral agents, certain protease inhibitor drugs, non-steroidal inflammatory drugs and convalescent plasma treatment were suggested. The containment and social distancing measures only aim at reducing the rate of new infections. In this view, we suggest certain traditional herbs and complementary and alternative medicine as a supporting public healthcare measure to boost the immune system and also may provide some lead to treat and prevent this infection.
This study investigated whether lower levels of eosinophil-related T helper 2 (Th2) cytokines are associated with coronary artery lesions in patients with Kawasaki disease. The researchers measured levels of interleukin (IL)-4, IL-5, eotaxin, and eosinophil cationic protein (ECP) in 95 Kawasaki disease patients before and after intravenous immunoglobulin (IVIG) treatment and compared them to 30 healthy controls. They found that higher levels of IL-5 and eosinophils after IVIG treatment were associated with a lower rate of coronary artery lesions. An increase in IL-5 and eosinophils levels after treatment, but not ECP, was inversely correlated with
This study investigated whether lower levels of eosinophil-related Th2 cytokines (IL-4, IL-5, eotaxin) and the eosinophil activation marker ECP are associated with coronary artery lesions (CAL) in patients with Kawasaki disease. The study found that:
1) KD patients had higher levels of eosinophils, IL-4, IL-5, eotaxin, and ECP compared to controls.
2) After IVIG treatment, levels of IL-4, IL-5, and eotaxin increased while ECP levels decreased.
3) Higher post-IVIG levels of eosinophils and IL-5
This document reviews potential pharmacologic treatments for COVID-19. It summarizes the virology of SARS-CoV-2 and potential drug targets, including viral entry proteins and immune pathways. Several repurposed drugs are discussed, including chloroquine/hydroxychloroquine which may inhibit viral entry and immune responses. Over 300 clinical trials are investigating potential COVID-19 treatments but currently no therapies have proven effective. The most promising is remdesivir, which has strong antiviral activity but requires further clinical trial evaluation.
This document reviews potential pharmacologic treatments for COVID-19. It summarizes the virology of SARS-CoV-2 and potential drug targets. Currently, there are no proven effective therapies but remdesivir shows promise based on in vitro activity. Over 300 clinical trials are investigating potential treatments including repurposed drugs like chloroquine/hydroxychloroquine and lopinavir/ritonavir. The review summarizes the mechanisms and pharmacology of select proposed treatments and provides an overview of ongoing clinical trials.
Application of ordinal logistic=China.pdfHenokBuno
This study aimed to identify determinants of illness severity for COVID-19 patients in China. Medical records from 598 COVID-19 patients admitted to four hospitals in China between January and March 2020 were analyzed. Patients were divided into moderate (n=400), severe (n=85), and critical (n=113) illness groups based on their condition. Ordinal logistic regression was used to identify predictors of more severe illness. The analysis found that older age, hypertension, abnormal liver enzymes and cardiac markers, longer time from illness onset to diagnosis and admission were associated with increased risk of more severe illness.
This document reviews potential pharmacologic treatments for COVID-19. It summarizes the virology of SARS-CoV-2 and potential drug targets. It reviews the in vitro activity and clinical experiences of repurposed drugs including chloroquine/hydroxychloroquine, lopinavir/ritonavir, and umifenovir. It also discusses investigational agents such as remdesivir. Over 300 clinical trials are evaluating potential COVID-19 treatments but currently no therapies have proven effective based on randomized clinical trial data.
Does Liuzijue Qigong affect anxiety in patients with chronic obstructive pulm...LucyPi1
Abstract Background: Anxiety is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), but no well-recognized method can provide effective relief. Liuzijue Qigong (LQG) is a traditional Chinese fitness method, based on breath pronunciation. This study aimed to examine the efficacy of LQG to relieve anxiety in COPD patients and to explore the factors that influence anxiety, including whether LQG is effective during the coronavirus disease 2019 (COVID-19) outbreak. Methods: We conducted an open-label, randomized, controlled, clinical trial. A total of 60 patients with stable COPD were randomly assigned to two groups. Both groups were given routine medical treatment, and the patients in the pulmonary rehabilitation (PR) group were given an extra intervention in the form of LQG, performed for 30 minutes each day for 12 weeks. Data collection was performed at baseline and 12 weeks (during the COVID-19 epidemic). The primary outcomes were the self-rating anxiety scale (SAS) scores, and the secondary outcomes were relevant information during the epidemic and analyses of the related factors that influenced SAS scores during the COVID-19 outbreak. Results: Compared with baseline, patients in both groups demonstrated varying degrees of improvements in their SAS scores (all P < 0.01). An analysis of covariance, adjusted for baseline scores, indicated that the SAS scores improved more dramatically in the PR group than in the control group (F = 9.539, P = 0.004). During the outbreak, the SAS scores for sleep disorder were higher than all other factors, reaching 1.38 ± 0.67, and the scores for “I can breathe in and out easily” for the PR group were lower than the scores for the control group (Z = −2.108, P = 0.035). Significant differences were identified between the two groups for the categories “How much has the outbreak affected your life”, “Do you practice LQG during the epidemic” and “Do you practice other exercises during the epidemic” (all P < 0.05). Compared with current reports, LQG had a relatively high adherence rate (80.95%). A multiple linear regression analysis revealed multiple predictors for SAS scores during the outbreak: group (b = −3.907, t = −3.824, P < 0.001), COPD assessment test score (b = 0.309, t = 2.876, P = 0.006), SAS score at baseline (b = 0.189, t = 3.074, P = 0.004), and living in a village (b = 4.886, t = 2.085, P = 0.043). Conclusion: LQG could effectively reduce the risks of anxiety among COPD patients, even during the COVID-19 outbreak. For those COPD patients with high COPD assessment test and high baseline SAS scores or who live in villages, we should reinforce the management and intervention of psychological factors during the epidemic.
This study analyzed hematological and biochemical markers in 249 patients hospitalized with COVID-19, of which 58 patients died. The key findings were:
1) Non-survivors had significantly higher neutrophil counts, procalcitonin, C-reactive protein, AST, serum potassium, prothrombin time, activated prothrombin time, and LDH compared to survivors.
2) Survivors had significantly higher lymphocyte counts and hemoglobin levels than non-survivors.
3) Patients with abnormal chest x-ray findings had significantly higher white blood cell counts, neutrophil counts, platelet counts, serum potassium, procalcitonin, C-reactive protein, AST, ALT
The document discusses the potential relationship between SARS-CoV-2 spike protein and increased risk of thrombosis (blood clots). It summarizes research showing the spike protein can directly activate platelets and promote blood clotting. This may explain the increased rates of thrombosis seen in severe COVID-19 cases. The spike protein's procoagulant activity is hypothesized to be a class effect of COVID-19 vaccines, and rapid development may have prevented long term safety testing needed to verify effects. Emerging evidence suggests some post-vaccination thrombosis cases have unusual features warranting further research into potential causal links between the vaccine and these rare events.
Similar to Network pharmacology studies on the effect of Chai-Ling decoction in coronavirus disease 2019 (20)
A comprehensive review on Polyalthia longifoliaLucyPi1
Abstract
Herbal plants act as a significant source for discovering new compounds with potential therapeutic activities.
Polyalthia longifolia, which is commonly known as an Indian mast tree, has various pharmacological properties,
such as an anticancer, ulcer protective, hypoglycemic, hypotensive, a corrosion inhibitor, a bio-adsorbent, and few
more. Moreover, it is known as false ashoka owing to its close resemblance with Saraca indica (ashoka tree).
Various compounds have been reported from the extract of some parts of the plant, such as leaves, bark, root, and
seeds. These extracts possess an ability to treat a number of human ailments, such as fever, ulcer, skin diseases,
helminthiasis, and cardiac problems. Studies performed on the leave extract shows evidence that some compounds
cause cell death in various cancer cell lines. The plant also has some biological applications, such as antibacterial,
antiviral, and antimicrobial, which makes it clinically significant and useful. This review is an effort to explore and
gather plant information in an organized manner. It reveals detailed information about the propagation, synonyms,
vernaculars, varieties of plant, medicinal significance, ecology and distribution, botanical and ethnobotanical
description, phytochemical constituents, and pharmacological activity of the plant.
Reliability and validity of the Tibetan medicine constitution scale: a cross-...LucyPi1
Abstract Background: The constitutional theory is an important aspect of Tibetan medicine, however a quantitative measurement tool for constitution identification still does not exist. The objective of this study is to evaluate the reliability and validity of a Tibetan medicine constitution scale (TMCS) that consists of three sub-scales and 31 items. Methods: From June to July 2019, 622 people from the general population in Beijing, China, aged 18 to 60 were investigated. We employed Cronbach’s alpha (α), split-half reliability, and test-retest reliability to determine the reliability of the scale. The content validity and contract validity of the TMCS were evaluated using factor analysis and correlation analysis based on Tibetan medicine theory. The items were screened according to the reliability test results. Results: After the items were screened, 22 items remained in the scale. The Cronbach’s alpha value for the internal consistency reliability of the TMCS was 0.754 (95% confidence interval (CI): 0.700–0.761). The correlation coefficient for the two-week test-retest of the total score was 0.726 (95% CI: 0.571–0.834). The split-half coefficient was 0.689 (95% CI: 0.640–0.734). The scale can be explained by eight potential factors, including morphological structure, physiological function, personality, adaptability, etc. The body mass index was negatively correlated with the score of the sub-rlung scale (r = − 0.376), slightly positively correlated with the sub-mkhris pa scale (r = 0.099), and positively correlated with the sub-bad kan scale (r = 0.362). Conclusion: The TMCS is a reliable and valid instrument that can be used to assess the body constitution of the general population in Beijing, China. Future studies are needed to explore the differences in biological characteristics among the constitutional types and the association between constitution and disease.
The riddles of number nine in Chinese medicine processing methodLucyPi1
Abstract The “nine cycles of steaming and shining”, “nine making”, “nine turns” and “nine cycles of calcining and quenching” methods that are recorded and used since ancient times are merely one aspect of the unique processing methods of traditional Chinese medicine. Inducing the Chinese medicine processing method “nine cycles of steaming and shining” from historical review and summarizing the practical wisdom based on the canonical aspects of traditional Chinese medicine and the experiences of ancient Chinese medicine sages to promote the new development of traditional Chinese medicine. After the long-term and multiple “nine” processing, the materials of traditional Chinese medicine exhibit significant beneficial changes in terms of taste, efficacy, and chemical composition contents, thus emphasizing that Chinese medicine processing plays a significant role in their efficacy enhancement and toxicity reduction. Heshouwu (Polygoni Multiflori Radix), Dihuang (Rehmanniae Radix), Huangjing (Rhizoma Polygonati), Dahuang (Radix et Rhizoma Rhei), and Xixiancao (Herba Siegesbeckiae) are representatives of Chinese medicinal materials prepared using the “nine-system” processing method. This review discovers the aim and the molecular mechanism of “nine” processing of the abovementioned herbs from the viewpoints of modern pharmacochemistry and pharmacology to provide a theoretical support for the “nine” processing method of traditional Chinese medicine and to promote the international market of traditional Chinese medicine.
Research progress in the use of leeches for medical purposesLucyPi1
Abstract Leeches are invertebrates that have a long history of application in the development of human medicine in both the East and the West. This paper comprehensively analyzes and evaluates current research and the latest progress with regard to the application of leeches, their medical value, and their application prospects from various perspectives, so as to provide a reference for new viewpoints and directions for research on leeches. Modern research has revealed that leeches contain various bioactive components, which have pharmacological effects such as anticoagulation, antithrombosis, blood viscosity reduction, and anti-atherosclerosis. Leech therapy is an important treatment approach for venous congestion after microsurgery and is also an effective adjuvant treatment for diabetic feet, chronic pain, and tumors. Therefore, leeches are of importance for the research and development of new drugs, the restoration of blood supply after surgery, and the adjuvant treatment of diseases accompanied by blood blocking. In addition, leeches can also be used as model organisms for research in evolutionary biology and invertebrate neurophysiology as well as in neurophysiological, behavioral, and functional studies.
Brucea javanica oil inhibits proliferation of hepatocellular carcinoma cells ...LucyPi1
Abstract Background: Brucea javanica oil (BJO), distributed primarily in Southeast Asia, has long been utilized as a therapeutic agent for treating malignancies. However, its anticancer mechanisms are not clearly understood. The objective of this study was to examine the mechanisms underlying its treatment of hepatocellular carcinoma cells. Methods: CCK8 assay was used to evaluate cell viability. Hoechst33342 staining and flow cytometry analyses were used to examine apoptosis. Mito-Tracker Red CMXRos kit was used to measure the membrane potential of mitochondria. ATP assay kit was used to evaluate ATP levels. Western blots were used to assess the presence of AKT, adenosine monophosphate-activated protein kinase, Caspase3, Caspase9, Bax, and Bcl-2. Results: BJO inhibited the proliferation of hepatocellular carcinoma cells HepG2 in a time- and dose-dependent manner. It induced apoptosis, with the percentage of cells treated with 50–150 μg/mL BJO increasing from 8.01% to 28.02% in a concentration-dependent manner (P < 0.05, when 50 μg/mL of BJO group compared with the control group; P < 0.001, when 100 or 150 μg/mL of BJO group compared with the control group). After exposed to BJO, the expression of C-caspase3, C-caspase9 and Bax upregulated while that of Bcl-2 downregulated. BJO suppressed the PI3K/AKT pathway and promoted phosphorylation of adenosine monophosphate-activated protein kinase, while repressing the phosphorylation of mechanistic target of rapamycin. Compared with treatment by BJO alone, the PI3K/AKT agonist 740Y-P increased the survival rate of HepG2 cells (P < 0.01) and attenuated the inhibitory effect of BJO on cell apoptosis (P < 0.05). Conclusion: BJO is capable of inhibiting proliferation of HepG2 cells and inducing apoptosis via the PI3K/AKT pathway.
Effect of Jianpi-yangwei decoction on gut fungi in the patients with gastric ...LucyPi1
Abstract Background: Our previous study shows that the empirical formula of Chinese medicine Jianpi-yangwei decoction (JYD) can improve the quality of life in patients with gastric cancer undergoing chemotherapy by increasing beneficial gut bacteria and decreasing harmful bacteria. The present study aims to investigate the effect of JYD on gut fungi in patients with gastric cancer undergoing chemotherapy. Methods: A total of 73 patients with gastric cancer undergoing chemotherapy were recruited. Twenty-nine patients in the chemotherapy group were given standard chemotherapy and 44 patients in the observation group were given JYD plus standard chemotherapy. A control group (55 cases) was recruited from the healthy medical examiners. After 3 months of treatment, life-quality score was evaluated and fecal microbiota was tested by high-throughput sequencing based on the 18S rRNA gene. Results: After treatment, life-quality score in the observation group was significantly lower than that in the chemotherapy group (P < 0.05). There was no significant difference between the observation and control groups’ diversity and richness indices of intestinal fungi. The Chao index for intestinal fungi in the chemotherapy group was significantly lower than that in the observation group (P < 0.05). There was a significant difference between the control and chemotherapy groups in the intestinal fungi according to Shannon and Simpson indices (P < 0.05). Linear discriminant analysis effect size analysis showed no significant differences among the three groups, but significant difference in intestinal fungi was observed between the observation group and the chemotherapy group. At the genus level, the relative abundance of the Aspergillus genus in the observation and control groups was significantly lower (P < 0.05), the relative abundance of the Cutaneotrichosporon, Galactomyces, and Ganoderma genus taxa was significantly higher compared with those in the chemotherapy group (P < 0.05), and there was no significant difference between the observation group and control group. Conclusion: JYD can ameliorate chemotherapy-induced fungal dysbacteriosis in patients with gastric cancer undergoing chemotherapy and improve the quality of life of patients.
The coastal medicinal plant Vitex rotundifolia: a mini-review on its bioactiv...LucyPi1
This document summarizes research on the coastal medicinal plant Vitex rotundifolia. It provides background on the plant's long history of traditional medicinal use in European and Asian countries to treat various ailments. The review focuses on the bioactive compounds (flavonoids, phenolic acids, terpenes) that have been isolated from V. rotundifolia and research on their pharmacological activities, such as anti-inflammatory and antioxidant effects. These compounds may be useful for developing new pharmaceuticals to treat disease.
International expert consensus on clinical application of traditional Chinese...LucyPi1
Abstract Guided by the theory of traditional Chinese medicine (TCM), TCM formula granules are made through the optimal process of extraction, concentration, drying, and granulation by combining modern new preparation technologies and pharmaceutical technologies. TCM formula granules are stable, safe, convenient, and effective. Compared with TCM decoction pieces, TCM formula granules can achieve the full process control of its industry chain from field to workshop and standardize the management of the origin of medicinal materials, processing of decoction pieces, processing technology, quality inspection, sales, and products distribution. TCM formula granules can partially replace Chinese patent medicines. Only available for around 800 common varieties of TCM, TCM formula granules cannot replace decoction pieces for many types which are not commonly used in clinical practice. A large number of formula granules are used in clinical and animal studies so that investigators no longer need to extract and control the quality of TCM decoction pieces. How to improve the production process, establish the quality standard, perfect the regulatory system, and expand the clinical application are the problems we need to solve as soon as possible for the better development of formula granules.
Bibliometric analysis of acupuncture research through the Web of Science data...LucyPi1
Abstract Background: The main points of focus of bibliometric analysis of acupuncture treatment of diseases include pain (headache, low back pain), insomnia, and knee osteoarthritis, for example. In this paper, we analyze the frontiers, hotspots, and research trends of acupuncture over the past 30 years and compare them for each of three 10-year periods. Methods: All the studies on acupuncture research in three different periods (1990–1999, 2000–2009, 2010–2019) were collected from the Web of Science database. The evolution of the research, hotspots, and trends in acupuncture were explored intuitively by analyzing the frequency, betweenness centrality, and subject word clustering of the three periods. Results: (1) 1990–1999, the main content relating to research was the mechanism of research of acupuncture treatment of pain. Naloxone was the high-frequency subject word, and centrality included, for example, the spinal cord, enkephalin, smoking cessation, and detoxification. The results of keyword cluster analysis showed that the main research content included capsaicin-induced neurogenic edema, chemical dependency treatment, afferent fiber, and sufferers from xerostomia. (2) 2000–2009, during this stage, the frequency of keywords appeared in new research content such as randomized controlled trials of acupuncture and low back pain, but pain still dominated the main research content. From the perspective of intermediary centrality, along with the rise in randomized controlled trials, there were many important meta-analyses, as well as the management of acupuncture treatment. The main elements of the keyword cluster analysis included, for example, systematic review, randomized controlled pilot study, add-on therapy, brief overview, and ovarian morphology. (3) 2010–2019, during this period, compared with the previous two stages, there was increased frequency of keywords, a growth in clinical randomized controlled trials, and distribution of centrality was evident in the emergence of acupuncture in care, osteoarthritis treatment, and breast cancer research. The keyword clustering covered, for example, neural specificity, inflammatory reaction, chronic pain, sleep pattern, and consort statement. Conclusion: This article summarizes the trend of development of acupuncture from 1990 to 2019 and compares the main research categories and hotspots in each of three different 10-year periods within this span, thereby helping elucidate the research direction within the field.
The dynamic changes and mechanisms of Rehmanniae radix processing based on Ma...LucyPi1
The document discusses research on the traditional Chinese medicine Rehmanniae radix (dihuang). It summarizes that Rehmanniae radix undergoes multiple steaming and drying cycles as part of traditional processing, which significantly increases levels of the Maillard reaction. The Maillard reaction occurs when amino acids and sugars react at high temperatures, producing flavors, colors, and potential health effects. The study analyzes changes in pH, color, amino acids, and other markers during processing to understand how the Maillard reaction impacts the processed herb. Thermal analysis techniques also examine the reaction's effects on the herb when it is carbonized. The goal is to scientifically explain the traditional processing method and how it transforms the raw herb
Investigation of in vitro antioxidant activity of dihydromyricetin and flavon...LucyPi1
Abstract Background: Vine tea from fermented Ampelopsis grossedentata leaves has been used as a herbal tea and folk medicine in the southern region of China for hundreds of years. The aim of this investigation was to analyze the total flavonoids found in vine tea, including three bioactive flavonoids, and the total phenolic contents in the aqueous methanol extracts of 10 vine tea samples. In addition, this study also aimed to examine the antioxidant activity of dihydromyricetin and vine tea’s flavonoid-rich extract. Methods: The total flavonoids and total phenolic content assay of extracts from vine tea were performed by ultraviolet-visible spectroscopy and epoch microplate spectrophotometer, respectively. Three bioactive flavonoids were quantified simultaneously using high performance liquid chromatography. The antioxidant activity of dihydromyricetin and vine tea’s flavonoid-rich extract was evaluated in vitro using six different methods. Results: Vine tea contained a large number of flavonoids, with dihydromyricetin as its main constituent. The flavonoid-rich extract exhibited a significant scavenging effect on superoxide anion radicals, and on 3-ethylbenzthiazoline-6-sulphonic acid and 1,1-diphenyl-2-picrylhydrazyl radicals. It also possessed definite activity in lipid peroxidation inhibition, ferric reduction, and the moderation of Fe2+ ion chelation ability. There was a significant negative correlation between dihydromyricetin content and antioxidant activity in the vine tea samples, including superoxide anion radical scavenging activity (P = −0.754, P < 0.05), lipid peroxidation inhibition activity (P = −0.759, P < 0.05), ferric-reducing antioxidant power (P = −0.843, P < 0.01), respectively. Dihydromyricetin played a dominant role in the antioxidant activities of the flavonoid-rich extract. Conclusion: Vine tea’s flavonoid-rich extract could be used as a new antioxidant source to safeguard against oxidative stress.
Advances in anti-inflammatory and immunoregulatory mechanisms of sinomenineLucyPi1
Abstract Sinomenine, a major active ingredient from traditional Chinese medicine Qingfengteng (Sinomenium acutum (Thunb.) Rehd.et Wils.), has been proven to have anti-inflammatory, analgesic, anti-tumor, immunomodulatory and other pharmacological effects, and is clinically used for various inflammatory and autoimmune diseases. However, due to complex molecular mechanisms and pathological characteristics in inflammatory and immune responses, the precise anti-inflammatory and immunological mechanisms of sinomenine are still unclear. This review summarizes the anti-inflammatory and immunoregulatory mechanisms of sinomenine during recent years in rheumatoid arthritis, respiratory system, nervous system, digestive system and organ transplant rejection. The molecular pharmacological mechanisms of sinomenine responsible for anti-inflammatory and immunosuppressive effects were in detail introduced based on 3 aspects including cytokines induction, signal pathways modulation and immune cells function regulation. Moreover, this review also raises some concerns and challenges in future sinomenine study, which will contribute to crucial theoretical and practical significance for in-depth development and utilization of sinomenine as medicinal resource.
Abstract Background: Non-alcoholic fatty liver disease (NAFLD) can cause insulin resistance (IR) and diabetes. Our previous studies have demonstrated that Jian-Gan-Xiao-Zhi decoction (JGXZ) could be effective for the treatment of NAFLD and IR. However, the possible mechanism underlying the effects of JGXZ on NAFLD and IR remains unknown. Methods: Fifty rats received a high-fat high-carbohydrate (HFHC) diet for 12 weeks to induce NAFLD. After 4 weeks of HFHC treatment, rats were orally treated with JGXZ (8, 16, and 32 g/kg weight) for 8 weeks. Ten rats in the control group received standard chow. In the positive control group, rats were orally treated with metformin (90 mg/kg weight) for 8 weeks. After JGXZ and metformin treatment, H&E staining was conducted on rat livers and serum biochemical markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and total cholesterol (TC), were measured using test kits. Moreover, a fasting blood glucose test and an oral glucose tolerance test (OGTT) were conducted. Serum levels of insulin were determined using ELISA kit, and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. The levels of total insulin receptor substrate-1 (IRS1), AMP-activated protein kinase-α (AMPKα) and c-Jun N-terminal kinase (JNK) as well as the levels of phosphorylation of IRS1 (p-IRS1), phosphorylation of AMPK (p-AMPK) and phosphorylation of JNK (p-JNK) were measured using western blotting. Results: The body weights in JGXZ low-, middle-, and high-dose groups were lower than those in the model group (P < 0.05, P < 0.01, P < 0.01, respectively). The serum levels of AST (P < 0.05 in JGXZ middle- and high-dose groups), ALT (P < 0.01 in JGXZ middle-dose group and P < 0.05 in JGXZ high-dose group), TG (P < 0.01 in JGXZ middle- and high-dose groups), and TC (P < 0.01) upon JGXZ treatment were lower those than in NAFLD model rats. H&E staining showed that JGXZ treatment reduced steatosis of the hepatocytes in NAFLD model rats. JGXZ decreased the levels of fasting blood glucose (P < 0.01), HOMA-IR (P < 0.01), AUC (area under the curve) of the OGTT (P < 0.05) and p-IRS1 (P < 0.01 in JGXZ middle- and high-dose groups, P < 0.05 in JGXZ low-dose groups). Moreover, JGXZ regulated the hepatic AMPKα/JNK pathway in NAFLD model rats, which reflected the induction of p-AMPKα and inhibition of p-JNK. Conclusion: This study showed that JGXZ improved liver function and reduced steatosis of the hepatocytes in NAFLD model rats. Moreover, JGXZ improved IR in NAFLD model rats. The possible mechanism underlying the effects of JGXZ on NAFLD and IR involves the modulation of the AMPK/JNK pathway.
Omics technology: an important tool in mechanism studies of Chinese herbal fo...LucyPi1
Identifying the active ingredients from natural herbal medicines and demonstrating their potential mechanisms are key points in the traditional Chinese medicine (TCM) field. In recent years, increasing studies have focused on the effects and mechanisms of Chinese herbal formulas. Basic studies on these formulas further coincide with the theory and practical use of TCM according to the clinical experiences for thousands of years. Single compounds have specific molecular structures; therefore, their methodologies in effect and mechanism studies are similar in both Western and Eastern medicines, making them more acceptable by researchers worldwide. On the contrary, the multicomponent, multitarget, and multipathway structures of Chinese formulas make it challenging to explore their mechanisms accurately where the routine method used in Western medicine studies would be inapplicable, which is the main reason for the unacceptance of Chinese herbal formulas by researchers worldwide and presents a huge obstacle to the modernization of TCM. With the rapid progress in basic TCM studies, scientific and technological innovations have achieved a breakthrough in TCM. Omic technology, a series of research methods based on high-throughput analysis and detection techniques in modern biological research system such as genomics, transcriptomics, proteomics, and metabolomics, evaluates thousands of targets and pathways rather than focusing on a single target or pathway and could screen the global changes in genes, proteins, metabolites, and other factors involved in the process of biological signaling transduction [1]. This is in agreement with the “holism” theory in TCM, which explains the overall mechanisms of Chinese herbal formulas comprehensively. In this study, we introduced the conventionally used omic technologies and their applications in research of mechanism studies of Chinese herbal formulas.
Gastrointestinal effects of Artemisia absinthium Linn. based on traditional P...LucyPi1
Abstract One of the most extensively used herbs in traditional Persian medicine (TPM) used in the treatment of gastrointestinal (GI) disorders, is the plant Artemisia absinthium Linn. (AAL). It also has a wide range of activities such as analgesic and anti-inflammatory, anti-oxidant, anti-fungal, and anti-bacterial activities, hepatoprotective, and neuroprotective activities in addition to having gastroprotective effects. This article is a review comparing TPM resources with new medicines. This review investigates this herb in major TPM sources and strives to extrapolate the exact function it serves in the digestive tract and compares the collected information on the function of AAL with information found in new medical resource databases such as ISI, Pubmed, Scopus, Google Scholar, and Scientific Information Database. AAL from the Asteraceae family of TPM, known as Afsentin, was used in the treatment of GI weaknesses, stomach pains, swellings, intestinal parasites, diarrhea, and vomiting. AAL increased appetite, so it was used for insect repellents and insecticide. Recent studies have indicated that the effects of this plant improved the symptoms of Crohn's disease and played a role in reducing inflammatory factors. It also has strong anti-parasitic, anti-insect, hepatoprotective, and antioxidant effects. Given the widespread use of AAL as a traditional medicine currently in use in different countries, particularly in the treatment of GI diseases, further clinical studies that focus on the therapeutic qualities of this plant are required in the future.
Jadwar (Delphinium denudatum Wall.): a medicinal plantLucyPi1
This review summarizes the medicinal uses of Delphinium denudatum Wall. (jadwar), according to historical documents and modern studies. Rhazes first documented its use in the 10th century to treat poisonings. Later, it was used for neurological, gastrointestinal, and other diseases. Modern studies show it has anti-microbial, anti-fatigue, anxiolytic, anticonvulsant, analgesic, and liver protective properties. The review focuses on therapeutic effects of its extracts and identifies phytochemicals that may underlie these effects, such as alkaloids and flavonoids. It concludes that controlled clinical trials are still needed to confirm effects against various diseases.
Effects of chicory (Cichorium intybus L.) on nonalcoholic fatty liver diseaseLucyPi1
Abstract There is a dramatic increase in the prevalence of nonalcoholic fatty liver disease, which is slowly turning into a pandemic as well as a major challenge across the world. Nonalcoholic fatty liver disease is described as a range of liver conditions such as fat accumulation, hepatic steatosis, or end-stage liver disease. Patients with nonalcoholic fatty liver disease are asymptomatic and their mortality is higher than people without nonalcoholic fatty liver disease. The pathogenesis of nonalcoholic fatty liver disease has not been clearly determined yet. The “two hits” hypothesis is designed to explain the pathogenesis of nonalcoholic fatty liver disease. Dyslipidemia, oxidative stress, insulin resistance, obesity, and chronic inflammation are some of the morbidities involved in the progression of nonalcoholic fatty liver disease. Chicory (Cichorium intybus L.) is an herbaceous perennial, known as chicory. Chicory contains various compounds, such as vitamins, sonchuside A, caffeic acid derivatives, fructo-oligosaccharides, chlorogenic acid, magnolialide, polysaccharides, coumarins, phenolic acids, terpenoids, flavonoids, polyphenol, cichoriosides, ixerisosides, eudesmanolides, inulin, bitter sesquiterpene lactones, and alkaloids. Current research has revealed that chicory supplementation might be effective in the treatment of nonalcoholic fatty liver disease. The anti-inflammatory, antihepatotoxic, antihyperlipidemic, antidiabetic, antihyperglycemic, and antioxidant properties of chicory provide plausible mechanisms by which chicory may affect the various steps of disease progression and severity. Existing studies have shown that chicory supplementation has beneficial effects on nonalcoholic fatty liver disease, but the existence of only one human study and possible side effects of chicory necessitate further studies.
Effects of herbal medicine in gastroesophageal reflux disease symptoms: a sys...LucyPi1
Abstract Background: Pyrosis and regurgitation are the cardinal symptoms of gastroesophageal reflux disease. Several herbs have been used for treating gastrointestinal disorders worldwide. This systematic review was conducted to investigate the effects of medicinal herbs on gastroesophageal reflux disease and adverse events. Methods: MEDLINE (via PubMed; The United States National Library of Medicine, USA), Scopus, ScienceDirect, Cochrane Central Register of Controlled Trials, Web of Science, Magiran, and Scientific Information Database were systematically searched for human studies, without a time frame, using medical subject heading terms such as “gastroesophageal reflux disease”, “reflux”, “esophagitis” and “herbs”. Manual searches completed the electronic searches. Results: Thirteen randomized controlled trials were identified, including 1,164 participants from 1,509 publications. In comparing herbal medicine to placebo, there were no significant differences in terms of heartburn (P = 0.23 and 0.48), epigastric or abdominal pain (P = 0.35), reflux syndrome (P = 0.12), and effective rate (P = 0.60), but there was a significant difference in terms of acid regurgitation (P = 0.01). In comparing herbal medicine to drugs, there was a significant difference in terms of effective rate (P = 0.001), and there was one trial that reported a significant difference in terms of epigastric pain (P = 0.00001). Also, in comparing herbal medicine to drugs, there were no significant differences in terms of acid regurgitation (P = 0.39). Conclusion: This meta-analysis showed that herbal medicines are effective in treating gastroesophageal reflux disease. Further standardized researches with a large-scale, multicenter, and rigorous design are needed.
Evaluation of scientific evidence for abortifacient medicinal plants mentione...LucyPi1
Abstract Background: Miscarriage or spontaneous ending to a pregnancy takes place at the early stages of pregnancy without intervention. Pregnant women may use medicinal herbs to relieve some of the symptoms of pregnancy as they believe that all herbs are safe. Some abortion-inducing herbs were mentioned by the famous Iranian philosophers, Avicenna and Aghili, in documents of traditional Persian medicine titled Al-Qanun Fi Al-Tibb (The Canon of Medicine, written by Avicenna in the 11th century) and Makhzan Al-adviyah (The Storehouse of Medicaments, written by Aghili in the 18th century). Methods: Electronic databases such as PubMed, Scopus, Google Scholar, Cochrane Library and Web of Science were searched to find new scientific evidence that these plants are toxic during pregnancy. Data was collected from 1831 to 2019. Results: Twenty-one plants were found to be abortive according to Al-Qanun Fi Al-Tibb (The Canon of Medicine) and Makhzan Al-adviyah (The Storehouse of Medicaments). Scientific research has shown that these plants possess abortifacient effects by the mechanisms of toxic alkaloids, uterine stimulants, and emmenagogue that interferes with implantation and results in fetus toxicity. These studies included in vivo or in vitro studies. Some of these plants showed abortifacient effects by more than one mechanism. Ruta graveolens, Nigella sativa, Curcuma longa, Lupinus termis, Apium graveolens, Mentha longifolia, and Peganum harmala possess uterine stimulant properties. Ruta graveolens, Juniperus sabina, Cicer arietinum, Piper longum, Artemisia absinthium, and Citrullus colocynthis interfere with implantation. Ruta graveolens, Nigella sativa, Curcuma longa, Tanacetum parthenium, Piper longum, Laurus nobilis, Apium graveolens, Mentha longifolia, and Cinnamomum iners exhibit emmenagogue effects. Lupinus termis, Delphinium staphisagria, Laurus nobilis, Trigonella foenum-graecum, Zataria multiflora, and Artemisia absinthium contain toxic alkaloids and possess teratogenic effects. Conclusion: The results of this study of traditional Persian medicine resources have been confirmed with new scientific evidence. Therefore, pregnant women should avoid consuming herbs without knowledge of their safety.
The potential effects of Caper (Capparis spinosa L.) in the treatment of diab...LucyPi1
Abstract Diabetic neuropathy (DN) is the most common form of neuropathy worldwide, with its prevalence rising alongside diabetes, and being characterized by sensory, motor or autonomic symptoms. DN is considered to be an incurable complication of diabetes, the management of which mainly consists of improving glycemic control, managing pain relief and ensuring continuous foot care. Although gabapentin, duloxetine and tricyclic antidepressants are commonly used to reduce patient symptoms, they do not affect the pathophysiology and progression of neuropathy. Furthermore, these drugs can have various side effects including insomnia, decreased appetite, arrhythmia, heart failure, and suicidal behavior. According to traditional Persian medicine, DN is recognized as a type of “Khadar” or “Esterkha” (a sensory or motor disorder, respectively) that occurs due to the accumulation of sugars in the peripheral nerves. Capparis spinosa L., commonly known as the caper plant, has been recommended in authentic sources of traditional Persian medicine to treat such disorders. In this study, we reviewed the pharmacological properties of C. spinosa using the Web of Science, PubMed, Scopus and Google Scholar databases, and found that Capparis spinosa L. could affect several pathways involved in DN pathogenesis, including aldose reductase activity, the secretion of inflammatory mediators (IL-17, TNF-α, IL-1β, IL-6), oxidative stress, hyperlipidemia, hyperglycemia and advanced glycation end product formation. Based on these findings, we hypothesize that Capparis spinosa L., may prevent the progression and reduce the symptoms of diabetic neuropathy, and so can be considered as a complementary treatment in this disorder. This hypothesis should be evaluated in well-designed in vitro and in vivo studies, and through clinical trials.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
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8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
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Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Our backs are like superheroes, holding us up and helping us move around. But sometimes, even superheroes can get hurt. That’s where slip discs come in.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Vestibulocochlear Nerve by Dr. Rabia Inam Gandapore.pptx
Network pharmacology studies on the effect of Chai-Ling decoction in coronavirus disease 2019
1. ARTICLE
TMR | May 2020 | vol. 5 | no. 3 | 145
doi: 10.12032/TMR20200324170
Submit a manuscript: https://www.tmrjournals.com/tmr
Traditional Chinese Medicine
Network pharmacology studies on the effect of Chai-Ling decoction in
coronavirus disease 2019
Lu Yang1#
, Yu-Ting Li2#
, Jing Miao3
, Li Wang4
, Hui Fu5
, Qin Li6
, Wei-Bo Wen6
, Zhai-Yi Zhang5
, Rui-Wen Song7
, Xiang-Guo Liu8
,
Hong-Wu Wang2
*, Huan-Tian Cui8
*
#
These authors are co-first authors on this work.
1
Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; 2
College of Traditional
Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; 3
Department of Integrated
Traditional and Western Medicine, Tianjin Second People’s Hospital, Tianjin 300192, China; 4
Department of Pharmacy,
Tianjin Second People’s Hospital, Tianjin 300192, China; 5
College of Integrated Chinese and Western Medicine, Tianjin
University of Traditional Chinese Medicine, Tianjin 301617, China; 6
Department of Endocrinology in Yunnan Provincial
Hospital of Traditional Chinese Medicine, Kunming 650021, China; 7
School of Management, Tianjin University of
Traditional Chinese Medicine, Tianjin 301617, China; 8
Shandong Provincial Key Laboratory of Animal Cell and
Developmental Biology, School of Life Sciences, Shandong University, Qingdao 250100, China.
*Corresponding to: Hong-Wu Wang. College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese
Medicine, No.10 Poyanghu Road, Jinghai District, Tianjin 301617, China. E-mail: whw2009@tjutcm.edu.cn; Huan-Tian Cui.
Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong
University, No. 72 Binhai Road, Jimo District, Qingdao 250100, China. E-mail: 1762316411@qq.com.
Highlights
The current study applied network pharmacology analysis and molecular docking method to study the
potential mechanisms of Chai-Ling decoction (CLD), an empirical formula derived from the classic ancient
prescription Xiao-Chai-Hu (XCH) decoction and Wu-Ling-San (WLS), on coronavirus disease 2019
(COVID-19).
Traditionality
The classic ancient prescription XCH and WLS decoctions originated from the ancient book of Chinese
medicine Shang Han Za Bing Lun (Treatise on Cold Damage Disorders, 200–210 C.E.), written by Zhang
Zhongjing. Previous studies have demonstrated that XCH can alleviate fever, cough, and fatigue, which
were the primary clinical outcomes of COVID-19. Besides, WLS decoction has shown apparent effects on
attenuating gastrointestinal symptoms. CLD, derived from a modification of XCH and WLS decoctions, is
used to treat the early-stage of COVID-19 in the Prevention and Treatment Guidelines of Damp-Heat
Syndrome of “Taiyin” Lung (respiratory system in the theory of traditional Chinese medicine) Epidemic
Disease (coronavirus pneumonia). However, the mechanisms of action of CLD in COVID-19 remain
unclear.
2. ARTICLE
TMR | May 2020 | vol. 5 | no. 3 | 146
doi: 10.12032/TMR20200324170
Submit a manuscript: https://www.tmrjournals.com/tmr
Abstract
Background: Chai-Ling decoction (CLD), derived from a modification of Xiao-Chai-Hu (XCH) decoction and
Wu-Ling-San (WLS) decoction, has been used to treat the early-stage of coronavirus disease 2019 (COVID-19).
However, the mechanisms of CLD in COVID-19 remain unknown. In this study, the potential mechanisms of CLD
in COVID-19 were preliminarily investigated based on network pharmacology and molecular docking method.
Methods: Initially, the active components and targets of CLD were screened based on Traditional Chinese
Medicine Systems Pharmacology Database and Analysis Platform and PharmMapper database. The targets of
COVID-19 were obtained from GeneCards database. The protein-protein interaction network was established using
STRING database to analyze the key targets. Gene Oncology (GO) analysis and Kyoto Encyclopedia of Genes and
Genomes analysis were also conducted to evaluate the pathways related to the targets of CLD on COVID-19.
Moreover, the compound-target-pathway network was established using Cytoscape 3.2.7. Subsequently, the
molecular docking method was performed to select the active compounds with high binding affinity on severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2), which is
the key target of SARS-CoV-2 in entering target cells. The possible binding sites were also visualized by a
three-dimensional graph. Results: Network pharmacology analysis showed that there were 106 active components
and 160 targets of CLD. Additionally, 251 targets related to COVID-19 were identified, and 24 candidates of CLD
on COVID-19 were selected. A total of 283 GO terms of CLD on COVID-19 were identified, and 181 pathways
were screened based on GO and Kyoto Encyclopedia of Genes and Genomes analyses. CLD might alleviate the
inflammatory response and improve lung injury to treat COVID-19 through interleukin 17 signaling, T helper cell
17 differentiation, tumor necrosis factor signaling, and hypoxia inducible factor-1 signaling. Besides, molecular
docking indicated that beta-sitosterol, kaempferol, and stigmasterol were the top three candidates in CLD with the
highest affinity to SARS-CoV-2 and ACE2. Conclusion: Our study identifies the potential mechanisms of CLD on
COVID-19 and beta-sitosterol, kaempferol, and stigmasterol may be the key compounds that exert antiviral effects
against SARS-CoV-2.
Keywords: Chai-Ling decoction, Coronavirus disease 2019, Network pharmacology, Molecular docking, Severe
acute respiratory syndrome coronavirus 2, Angiotensin-converting enzyme 2
Acknowledgments:
This study was supported by university-level project on curing disease in 2018 of Tianjin University of
Traditional Chinese Medicine (XJ201801).
Abbreviations:
CLD, Chai-Ling decoction; XCH, Xiao-Chai-Hu; WLS, Wu-Ling-San; COVID-19, coronavirus disease 2019;
SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ACE2, angiotensin-converting enzyme 2; GO,
Gene Oncology; S protein, spike protein; TCM, traditional Chinese medicine; TCMSP, Traditional Chinese
Medicine Systems Pharmacology Database and Analysis Platform; OB, oral bioavailability; DL, drug-like; PPI,
protein-protein interaction; KEGG, Kyoto Encyclopedia of Genes and Genomes; IL, interleukin; TNF, tumor
necrosis factor; CCL, C-C motif ligand; MAPK, mitogen-activated protein kinase; CCs: cell components; MFs:
molecular functions; BPs: biological processes; HIF-1, hypoxia inducible factor-1; Th17, T helper cell 17.
Competing interests:
There are no conflicts of interest.
Citation:
Lu Yang, Yu-Ting Li, Jing Miao, et al. Network pharmacology studies on the effect of Chai-Ling decoction in
coronavirus disease 2019. Traditional Medicine Research 2020, 5 (3): 145–159.
Executive Editor: Nuo-Xi Pi.
Submitted: 14 March 2020, Accepted: 24 March 2020, Online: 28 March 2020.
3. ARTICLE
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doi: 10.12032/TMR20200324170
Background
Since December 2019, a number of coronavirus
disease 2019 (COVID-19) cases have been detected in
various provinces and cities in China, and the disease
quickly spread many foreign countries and regions [1].
Following severe acute respiratory syndrome (SARS)
and Middle East respiratory syndrome, the worldwide
epidemic of COVID-19 has become one of the
significant threats to human health and public safety.
Fever, dry cough, and fatigue are major clinical
symptoms of COVID-19. Besides, some patients also
exhibit myocardial, digestive, and neurological damage.
Currently, no effective antiviral drug on COVID-19
has been developed. It remains unclear whether the
drugs discovered, such as protease inhibitor indinavir,
saquinavir, and kyprolis, have a definite effect on
COVID-19. Although remdesivir has been shown to
inhibit the replication of severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2), further
evidence is still needed. Besides, other possible drugs
for COVID-19, including arbidol and darunavir, have
shown low bioactivity. Zhou. et al found that
SARS-CoV-2 mainly infected target cells by binding
the spike protein (S protein) on the envelope to
angiotensin-converting enzyme 2 (ACE2) [2], which is
the receptor on the surface of target cells, similar to
SARS-CoV [3]. ACE2 is a type I transmembrane
protein composed of 805 amino acids, mainly
distributes in the lung, kidney, testicle, heart, and other
tissues. Disrupting the binding of S protein and ACE2
could be a therapeutic target of COVID-19 [4].
Traditional Chinese medicine (TCM) has
accumulated abundant experience in the prevention
and treatment of infectious diseases and shown
beneficial effects on COVID-19. Studies indicate that
TCM can decrease the transformation of mild to severe
cases [5]. Qing Fei Pai Du decoction, which is a
modification of Xiao-Chai-Hu (XCH) decoction,
Wu-Ling-San (WLS), Ma Xing Shi Gan decoction, and
She Gan Ma Huang decoction in Shang Han Za Bing
Lun (Treatise on Cold Damage Disorders, 200–210
C.E.), has shown 90% effective rate on COVID-19 [6].
Previous studies have demonstrated that XCH (Chaihu
(Bupleuri Radix), Banxia (Pinelliae Rhizoma),
Renshen (Panax Ginseng C. A. Mey), Gancao
(Glycyrrhizae Radix et Rhizoma), Huangqin
(Scutellariae Radix), Shengjiang (Zingiberis Rhizoma
Recens), and Dazao (Jujubae Fructus)) can alleviate
fever [7], cough [8], and fatigue [9], the primary
clinical outcomes of COVID-19. According to the
Diagnosis and treatment program of TCM on
COVID-19 in Hunan (China), XCH can be used to
treat patients with COVID-19 with bitter taste, hiccup,
and fever [10]. Additionally, WLS decoction (Guizhi
(Cinnamomi Ramulus), Fuling (Poria), Zhuling
(Polyporus), Zexie (Alismatis Rhizoma), and Baizhu
(Atractylodis Macrocephalae Rhizoma)) has shown
apparent effects on attenuating gastrointestinal
symptoms [11].
Chai-Ling decoction (CLD) (Chaihu 24 g (Bupleuri
Radix), Huangqin 9 g (Scutellariae Radix), Guizhi 6–9
g (Cinnamomi Ramulus), Baizhu 9 g (Atractylodis
Macrocephalae Rhizoma), Fuling 10 g (Poria),
Zhuling 10 g (Polyporus), Zexie 9 g (Alismatis
Rhizoma), Gancao 6 g (Glycyrrhizae Radix et
Rhizoma), Shishangbai 30 g (Selaginella Doederleinii),
and Lianqiao 30 g (Forsythiae Fructus)) was derived
from a modification of XCH and WLS decoctions,
which originated from Shang Han Za Bing Lun
(Treatise on Cold Damage Disorders, 200–210 C.E.)
written by Zhang Zhongjing . Moreover, CLD has been
shown to have anti-inflammatory, anticoagulant,
antioxidant, hypoglycemic, immunomodulatory, and
diuretic effects and used in the treatment of liver,
kidney, and joint diseases [12]. According to the
Prevention and Treatment Guidelines of Damp-Heat
Syndrome of “Taiyin” Lung (respiratory system in the
theory of traditional Chinese medicine) Epidemic
Disease (coronavirus pneumonia), CLD could be used
to treat the early stage of COVID-19 [13].
Due to the multiple targets and components of TCM,
network pharmacology has been used as an essential
tool to identify the key targets and mechanisms of
TCM [14]. The molecular docking method can be used
to analyze the interactions between drug components
and targets protein to investigate the binding affinity
and predict the possible binding sites of drugs [15]. In
this study, the active components of CLD were
screened through network pharmacology, and the
potential targets and mechanisms of CLD in
COVID-19 were predicted. The molecular docking
method was used to identify the key compounds in
CLD with high binding affinity on the SARS-CoV-2
and ACE2, which is the key target of SARS-CoV-2 in
entering target cells.
Materials and methods
Identification of the main active compounds
The main compounds in CLD were screened based on
the Traditional Chinese Medicine Systems
Pharmacology Database and Analysis Platform
(TCMSP) (http://tcmspw.com/tcmsp.php) and
literatures, and Chaihu (Bupleuri Radix), Huangqin
(Scutellariae Radix), Guizhi (Cinnamomi Ramulus),
Baizhu (Atractylodis Macrocephalae Rhizoma), Fuling
(Poria), Zhuling (Polyporus), Zexie (Alismatis
Rhizoma), Gancao (Glycyrrhizae Radix et Rhizoma),
Shishangbai (Selaginella Doederleinii), and Lianqiao
(Forsythiae Fructus) were used as keywords to query
the candidate components of CLD. Compounds with
an oral bioavailability (OB) ≥ 30% are considered to
be absorbed and utilized by the human body [16].
Drug-like (DL) is a necessary condition for the
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preparation of compound medicine. The DL value
represents the similarity between the composition and
known chemical medicine. It is generally considered
that the composition with DL value ≥ 0.18 has an
important reference value for the activity of the body
[17]. The OB and DL values of each compound can be
directly obtained in the TCMSP, and the effective
components of CLD were obtained by screening for
OB ≥ 30% and DL value ≥ 0.18.
Prediction of potential targets and annotation of
gene names
Reverse pharmacophore search was used to identify
the targets with a high binding affinity with drug
components. Initially, the molecular structures of
compounds identified from CLD were matched
reversely to the pharmacophore database. The
chemical composition obtained in 1.1 was imported
into the PubChem database
(https://pubchem.ncbi.nlm.nih.gov/) by name, and the
three-dimensional structure of each component were
obtained and stored in sdf format and uploaded to the
PharmMapper (http://www.lilab-ecust.cn/pharmmappe
r/) to obtain human-related protein targets for active
ingredients [18]. The UniProt database
(https://www.uniprot.org/) was used to obtain the
relative gene name of each target.
Potential targets for prediction of the disease
Novel coronavirus pneumonia was used as the
keyword and imported to the GeneCards database
(https://www.genecards.org) to identify the key targets
of COVID-19 [19]. The targets of CLD components
and COVID-19 were intersected using Venny (version
2.1, http://bioinfogp.cnb.csic.es/tools/venny/) to obtain
the key targets of CLD on COVID-19.
Protein-protein interaction (PPI) analysis and
identification of key targets
STRING (https://string-db.org) can be used to study
the PPI [20]. The potential targets of CLD in
COVID-19 were imported into the STRING database
to obtain the PPI among each target. According to the
PPI network, proteins with high connectivity showed
larger numbers and width of connections. Key targets
with the top five connectivity were identified as the
key targets.
Pathway enrichment using Gene Oncology (GO)
analysis
GO analysis of targets of CLD on COVID-19 was
conducted using DAVID database
(http://www.david.niaid.nih.gov). DAVID database can
provide detailed annotations of pathways, including
cell components (CCs), molecular functions (MFs),
and biological processes (BPs) [21]. Pathways with P
≤ 0.05 and q ≤ 0.05 were obtained.
Pathway enrichment using Kyoto Encyclopedia of
Genes and Genomes (KEGG)
Targets of CLD on COVID-19 were imported into the
KOBAS 3.0 database (http://kobas.cbi.pku.edu.cn) to
obtain the KEGG terms. Pathways that may be
involved in COVID-19 with P ≤ 0.05 and q ≤ 0.05
were identified, and the top ten KEGG pathways with
low P-value were selected as the potential pathways of
CLD on COVID-19.
Establishment of compound-target-pathway
network
Cytoscape 3.7.2 was used to generate the
compound-target-pathway network of CLD on
COVID-19 [22]. According to the
compound-target-pathway network, different active
compounds, targets, and pathways were visualized
with the nodes in different colors.
Molecular docking of major components in CLD
with SARS-CoV-2 and ACE2
The three-dimensional structures of S protein of
SARS-CoV-2 (PDB ID, 6LU7) and ACE2 (PDB ID,
IR42) were downloaded in the RCSB database
(https://www.rcsb.org/) and saved as pdb format. The
three-dimensional structures of S protein in
SARS-CoV-2 and ACE2 were added with hydrogen,
electron, and ROOT using AutoDock software. The top
20 candidate compounds in CLD were selected for
molecular docking, and the results of molecular
docking were visualized using PyMOL software.
Results
Results of chemical compounds in CLD
A total of 1,068 compounds were obtained from the
TCMSP, including 288 from Chaihu (Bupleuri Radix),
58 from Huangqin (Scutellariae Radix), 280 from
Gancao (Glycyrrhizae Radix et Rhizoma), 106 from
Guizhi (Cinnamomi Ramulus), 55 from Baizhu
(Atractylodis Macrocephalae Rhizoma), 34 from
Fuling (Poria), 31 from Zhuling (Polyporus), 46 from
Zexie (Alismatis Rhizoma), 20 from Shishangbai
(Selaginella Doederleinii), and 150 from Lianqiao
(Forsythiae Fructus). After removing the duplicated
compounds, 106 active compounds in CLD with OB ≥
30% and DL ≥ 0.18 were selected. Based on the
literature, compounds that could not be detected by
mass spectrum were removed and 106 compounds
were identified as the main compounds of CLD,
including 12 from Lianqiao (Forsythiae Fructus) [23],
6 from Zexie (Alismatis Rhizoma) [24], 1 from
Shishangbai (Selaginella Doederleinii) [25], 5 from
Zhuling (Polyporus) [26], 9 from Fuling (Poria) [27],
4 from Baizhu (Atractylodis Macrocephalae Rhizoma)
[28], 3 from Guizhi (Cinnamomi Ramulus) [29], 14
from Huangqin (Scutellariae Radix) [30], 6 from
Chaihu (Bupleuri Radix) [31], and 46 from Gancao
(Glycyrrhizae Radix et Rhizoma) [32–34]. The detailed
information of selected active compounds is presented
in Table 1.
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Table 1 Information of active compounds in CLD
MOL_ID Molecule_name OB (%) DL Herb Node
MOL000006 Luteolin 36.16 0.25 FF M1
MOL000098 Quercetin 46.43 0.28 FF, BR, GRER M2
MOL000173 Wogonin 30.68 0.23 FF, SR M3
MOL000358 Beta-sitosterol 36.91 0.75 FF, CR, SR M4
MOL000422 Kaempferol 41.88 0.24 FF, BR, GRER M5
MOL003295 (+)-Pinoresinol monomethyl ether 53.08 0.57 FF M6
MOL003305 Phillyrin 36.4 0.86 FF M7
MOL003306 ACon1_001697 85.12 0.57 FF M8
MOL003322 Forsythinol 81.25 0.57 FF M9
MOL003330 (-)-Phillygenin 95.04 0.57 FF M10
MOL003347 Hyperforin 44.03 0.6 FF M11
MOL003348 Adhyperforin 44.03 0.61 FF M12
MOL000359 Sitosterol 36.91 0.75 SD, AR, CR, SR, GRER M13
MOL000830 Alisol B 34.47 0.82 AR M14
MOL000831 Alisol B monoacetate 35.58 0.81 AR M15
MOL000832 Alisol B 23-acetate 32.52 0.82 AR M16
MOL000853 Alisol B 36.76 0.82 AR M17
MOL000854 Alisol C 32.7 0.82 AR M18
MOL000856 Alisol C monoacetate 33.06 0.83 AR M19
MOL000816 Ergosta-7,22-dien-3-one 44.88 0.72 PO M20
MOL000817 Ergosta-5,7,22-trien-3-ol 46.18 0.72 PO M21
MOL000820 Polyporusterone E 45.71 0.85 PO M22
MOL000822 Polyporusterone G 33.43 0.81 PO M23
MOL011169 Peroxyergosterol 44.39 0.82 PO M24
MOL000276 7,9(11)-Dehydropachymic acid 35.11 0.81 P M25
MOL000283 Ergosterol peroxide 40.36 0.81 P M26
MOL000287
3Beta-hydroxy-24-methylene-8-lanostene-
21-oic acid
38.7 0.81 P M27
MOL000289 Pachymic acid 33.63 0.81 P M28
MOL000290 Poricoic acid A 30.61 0.76 P M29
MOL000291 Poricoic acid B 30.52 0.75 P M30
MOL000292 Poricoic acid C 38.15 0.75 P M31
MOL000296 Hederagenin 36.91 0.75 P M32
MOL000300 Dehydroeburicoic acid 44.17 0.83 P M33
MOL000021
14-Acetyl-12-senecioyl-2E,8E,10E-atract
ylentriol
60.31 0.31 AMR M34
MOL000022
14-Acetyl-12-senecioyl-2E,8Z,10E-atract
ylentriol
63.37 0.3 AMR M35
MOL000049 3β-Acetoxyatractylone 54.07 0.22 AMR M36
MOL000072 8β-Ethoxy atractylenolide Ⅲ 35.95 0.21 AMR M37
MOL000073 ent-Epicatechin 48.96 0.24 CR M38
MOL000492 (+)-Catechin 54.83 0.24 CR M39
MOL001736 (-)-Taxifolin 60.51 0.27 CR M40
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Table 1 Information of active compounds in CLD (Continued)
MOL_ID Molecule_name OB (%) DL Herb Node
MOL000228
(2R)-7-Hydroxy-5-methoxy-2-
phenylchroman-4-one
55.23 0.2 SR M41
MOL000525 Norwogonin 39.4 0.21 SR M42
MOL000552 5,2'-Dihydroxy-6,7,8-trimethoxyflavone 31.71 0.35 SR M43
MOL001689 Acacetin 34.97 0.24 SR M44
MOL002714 Baicalein 33.52 0.21 SR M45
MOL002908 5,8,2'-Trihydroxy-7-methoxyflavone 37.01 0.27 SR M46
MOL002909
5,7,2,5-Tetrahydroxy-8,6-
dimethoxyflavone
33.82 0.45 SR M47
MOL002917 5,2',6'-Trihydroxy-7,8-dimethoxyflavone 45.05 0.33 SR M48
MOL002925 5,7,2',6'-Tetrahydroxyflavone 37.01 0.24 SR M49
MOL002927 Skullcapflavone II 69.51 0.44 SR M50
MOL002928 Oroxylin a 41.37 0.23 SR M51
MOL002932 Panicolin 76.26 0.29 SR M52
MOL002933 5,7,4'-Trihydroxy-8-methoxyflavone 36.56 0.27 SR M53
MOL002934 Neobaicalein 104.3 0.44 SR M54
MOL000354 Isorhamnetin 49.6 0.31 BR, GRER M55
MOL000449 Stigmasterol 43.83 0.76 BR M56
MOL002776 Baicalin 40.12 0.75 BR M57
MOL004598
3,5,6,7-Tetramethoxy-2-(3,4,5-
trimethoxyphenyl)chromone
31.97 0.59 BR M58
MOL004609 Areapillin 48.96 0.41 BR M59
MOL004648 Troxerutin 31.6 0.28 BR M60
MOL000239 Jaranol 50.83 0.29 GRER M61
MOL000392 Formononetin 69.67 0.21 GRER M62
MOL000417 Calycosin 47.75 0.24 GRER M63
MOL000497 Licochalcone a 40.79 0.29 GRER M64
MOL000500 Vestitol 74.66 0.21 GRER M65
MOL001484 Inermine 75.18 0.54 GRER M66
MOL001792 DFV 32.76 0.18 GRER M67
MOL002311 Glycyrol 90.78 0.67 GRER M68
MOL002565 Medicarpin 49.22 0.34 GRER M69
MOL003896 7-Methoxy-2-methyl isoflavone 42.56 0.2 GRER M70
MOL004328 Naringenin 59.29 0.21 GRER M71
MOL004808 Glyasperin B 65.22 0.44 GRER M72
MOL004810 Glyasperin F 75.84 0.54 GRER M73
MOL004811 Glyasperin C 45.56 0.4 GRER M74
MOL004815
(E)-1-(2, 4-Dihydroxyphenyl)-3-(2,
2-dimethylchromen-6-yl)prop-2-en-1-one
39.62 0.35 GRER M75
MOL004827 Semilicoisoflavone B 48.78 0.55 GRER M76
MOL004828 Glepidotin A 44.72 0.35 GRER M77
MOL004829 Glepidotin B 64.46 0.34 GRER M78
MOL004833 Phaseolinisoflavan 32.01 0.45 GRER M79
MOL004841 Licochalcone B 76.76 0.19 GRER M80
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CLD, Chai-Ling decoction; BR, Bupleuri Radix (Chaihu); SR, Scutellariae Radix (Huangqin); CR, Cinnamomi
Ramulus (Guizhi); AMR, Atractylodis Macrocephalae Rhizoma (Baizhu); P, Poria (Fuling); PO, Polyporus
(Zhuling); AR, Alismatis Rhizoma (Zexie); GRER, Glycyrrhizae Radix et Rhizoma (Gancao); SD, Selaginella
Doederleinii (Shishangbai); FF, Forsythiae Fructus (Lianqiao).
Identification of the targets of CLD on COVID-19
Initially, 160 active ingredient targets were generated
using PubChem and PharmMapper databases. The
relative gene names of targets were obtained using
UniProt database. Then, 251 targets of COVID-19
were identified according to the GeneCards database.
After intersecting the targets of CLD in COVID-19, 24
potential targets of CLD in COVID-19 were obtained
(Figure 1).
Establishment and analysis of PPI network
Generally, 24 target protein nodes and 181 interaction
edges were obtained using PPI network analysis. The
average degree of target protein was 15.1. According
to the connectivity of target proteins, IL6, tumor
necrosis factor (TNF), C-C motif ligand (CCL) 2,
mitogen-activated protein kinase (MAPK) 1, and
MAPK3 were identified as the key targets of CLD in
COVID-19 (Figure 2).
GO analysis of common targets
Generally, 283 GO terms with P ≤ 0.05 and q ≤ 0.05
were generated to be related to the targets of CLD in
COVID-19, including 229 BPs terms, 22 CCs terms,
and 32 MFs terms. Lipopolysaccharide-mediated
signaling pathway and positive regulation of nitric
oxide biosynthetic process were the top two GO terms
in BPs with low P-value. Caveola and extracellular
space were the top two GO terms in CCs with low
P-value. Enzyme binding and MAP kinase activity
were the top two GO terms in MF with low P-value
(Figure 3).
KEGG analysis of targets of CLD in COVID-19
Table 1 Information of active compounds in CLD (Continued)
MOL_ID Molecule_name OB (%) DL Herb Node
MOL004848 Licochalcone G 49.25 0.32 GRER M81
MOL004855 Licoricone 63.58 0.47 GRER M82
MOL004856 Gancaonin A 51.08 0.4 GRER M83
MOL004879 Glycyrin 52.61 0.47 GRER M84
MOL004883 Licoisoflavone 41.61 0.42 GRER M85
MOL004884 Licoisoflavone B 38.93 0.55 GRER M86
MOL004885 Licoisoflavanone 52.47 0.54 GRER M87
MOL004903 Liquiritin 65.69 0.74 GRER M88
MOL004908 Glabridin 53.25 0.47 GRER M89
MOL004910 Glabranin 52.9 0.31 GRER M90
MOL004911 Glabrene 46.27 0.44 GRER M91
MOL004912 Glabrone 52.51 0.5 GRER M92
MOL004915 Eurycarpin A 43.28 0.37 GRER M93
MOL004917 Glycyroside 37.25 0.79 GRER M94
MOL004924 (-)-Medicocarpin 40.99 0.95 GRER M95
MOL004949 Isolicoflavonol 45.17 0.42 GRER M96
MOL004957 HMO 38.37 0.21 GRER M97
MOL004959 1-Methoxyphaseollidin 69.98 0.64 GRER M98
MOL004961 Quercetin der. 46.45 0.33 GRER M99
MOL005000 Gancaonin G 60.44 0.39 GRER M100
MOL005001 Gancaonin H 50.1 0.78 GRER M101
MOL005007 Glyasperins M 72.67 0.59 GRER M102
MOL005008 Glycyrrhiza flavonol A 41.28 0.6 GRER M103
MOL005012 Licoagroisoflavone 57.28 0.49 GRER M104
MOL005013 18α-Hydroxyglycyrrhetic acid 41.16 0.71 GRER M105
MOL005020 Dehydroglyasperins C 53.82 0.37 GRER M106
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A total of 181 KEGG terms were enriched as the
potential pathways of CLD in COVID-19. The top ten
pathways with high significance were selected and
presented in Table 2. interleukin (IL)-17 signaling
pathway, TNF signaling pathway, hypoxia inducible
factor-1 (HIF-1) signaling pathway, and the
differentiation of T helper cell 17 (Th17) were related
to the potential therapeutic pathway of CLD in
COVID-19.
Compound-target-pathway network construction
The compounds, targets, and pathways of CLD in
COVID-19 were imported into Cytoscape 3.7.2 to
generate the compound-target-pathway network.
According to the compound-target-pathway network,
red nodes represent the genes, orange nodes represent
pathways, light green nodes represent the active
ingredients of Chaihu (Bupleuri Radix), purple nodes
represent active ingredient of Huangqin (Scutellariae
Radix), light yellow nodes represent active ingredients
of Lianqiao (Forsythiae Fructus), light blue nodes
represent active ingredients of Gancao (Glycyrrhizae
Radix et Rhizoma), and pink nodes represent the active
ingredients of Guizhi (Cinnamomi Ramulus), Baizhu
(Atractylodis Macrocephalae Rhizoma), Fuling (Poria),
Zhuling (Polyporus), Zexie (Alismatis Rhizoma),
Shishangbai (Selaginella Doederleinii) (Figure 4).
Figure 1 Common targets of CLD in COVID-19. CLD, Chai-Ling decoction; COVID-19, coronavirus disease
2019.
Figure 2 PPI network of target proteins. PPI, protein-protein interaction.
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Figure 3 GO enrichment analysis of the common targets. GO, Gene oncology.
- log (p)
- log (p)
- log (p)
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Table 2 KEGG enrichment analysis of the common targets
KEGG, Kyoto Encyclopedia of Genes and Genomes; IL, interleukin; HIF-1, hypoxia inducible factor-1; TNF,
tumor necrosis factor; Th17, T helper cell 17.
Figure 4 Compound-target-pathway network of CLD in COVID-19. Red nodes represent the genes, orange
nodes represent pathways, light green nodes represent the active ingredients of Chaihu (Bupleuri Radix), purple
nodes represent active ingredient of Huangqin (Scutellariae radix), light yellow nodes represent active ingredients
of Lianqiao (Forsythiae Fructus), light blue nodes represent active ingredients of Gancao (Glycyrrhizae Radix et
Rhizoma), and pink nodes represent the active ingredients of Guizhi (Cinnamomi Ramulus), Baizhu (Atractylodis
Macrocephalae Rhizoma), Fuling (Poria), Zhuling (Polyporus), Zexie (Alismatis Rhizoma), Shishangbai
(Selaginella Doederleinii).
CLD, Chai-Ling decoction; COVID-19, coronavirus disease 2019.
No. Pathways Numbers of genes - log (p)
1 Human cytomegalovirus infection 12 22.22
2 IL-17 signaling pathway 10 21.29
3 Tuberculosis 10 18.58
4 Endocrine resistance 9 18.54
5 C-type lectin receptor signaling pathway 9 18.32
6 HIF-1 signaling pathway 9 18.14
7 TNF signaling pathway 9 18.04
8 NOD-like receptor signaling pathway 9 16.30
9 T cell receptor signaling pathway 8 15.90
10 Th17 cell differentiation 8 15.78
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Molecular docking analysis of active components in
CLD with SARS-CoV-2 and ACE2
Compounds with high connectivity are associated with
more targets. According to the number of related
targets, the top 20 active compounds in CLD with high
connectivity in compound-target-pathway network
were selected for molecular docking. Besides, ten
Western medicine compounds (arbidol, atazanavir,
darunavir, indinavir, kyprolis, lopinavir, remdesivir,
ritonavir, saquinavir, and tipranavir), which have been
reported to be possibly used in COVID-19 treatment in
Shanghai Institute of Materia Medica, were used as
positive control for molecular docking based on the
news report (http://www.simm.cas.cn/xwzx/kydt/2020
01/t20200125_5494417.html). Based on the docking
score, a lower docking score indicates a stronger
binding affinity to target protein. Beta-sitosterol,
kaempferol, and stigmasterol had the strongest affinity
with SARS-CoV-2 and ACE2. Moreover, their affinity
with SARS-CoV-2 and ACE2 was better than some of
these Western medicine compounds (Table 4 and
Figures 5–6).
Table 4 Molecular docking table of ACE2 and SARS-CoV-2 with 20 active components in CLD and 10
Western medicine compounds
ACE2, angiotensin-converting enzyme 2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; CLD,
Chai-Ling decoction.
Compound
Molecular
formula
Binding energy values
(SARS-CoV-2)
Binding energy
values (ACE2)
Luteolin C15H10O6 − 7.4 − 8.8
Quercetin C15H10O7 − 7.5 − 9.0
Wogonin C16H12O5 − 6.7 − 8.8
Mairin C30H48O3 − 7.4 − 9.6
Beta-sitosterol C30H52O − 8.1 − 10.9
Kaempferol C15H10O6 − 7.8 − 10.4
Arctiin C27H34O11 − 7.3 − 9.9
Bicuculline C20H17NO6 − 7.5 − 8.6
(3R,4R)-3,4-bis[(3,4-dimet
hoxyphenyl)methyl]oxolan-
2-one
C13H22O − 6.5 − 8.7
(+)-Pinoresinol
monomethyl ether
C27H34O11 − 6.9 − 8.9
Phyllyrin C27H34O11 − 7.1 − 9.4
Forsythinol C21H24O6 − 4.8 − 5.6
(-)-Phillygenin C21H24O6 − 6.9 − 9.0
β-Amyrin acetate C32H52O2 − 7.7 − 6.5
Hyperforin C35H52O4 − 5.9 − 9.1
Onjixanthone I C16H14O6 − 6.5 − 7.9
Stigmasterol C29H48O − 7.7 − 9.8
Yangambin C24H30O8 − 6.3 − 8.2
Alisol b C28H44O4 − 7.6 − 9.7
Alisol, b, 23-acetate C31H47O6 − 6.9 − 9.7
Arbidol C22H26BrClN2O3S − 6.5 − 8.2
Atazanavir C38H52N6O7 − 7.7 − 12.4
Darunavir C27H37N3O7S − 7.6 − 9.6
Indinavir C36H47N5O4 − 8.2 − 10.9
Kyprolis C40H57N5O7 − 7.3 − 10.2
Lopinavir C37H48N4O5 − 9.1 − 10.8
Remdesivir C27H35N6O8P − 7.5 − 11.0
Ritonavir C37H48N6O5S2 − 8.0 − 9.9
Saquinavir C38H50N6O5 − 8.9 − 11.7
Tipranavir C31H33F3N2O5S − 7.7 − 11.7
12. ARTICLE
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Figure 5 Molecular docking diagram of ACE2 with β-sitosterol, kaempferol, and stigmasterol. ACE2,
angiotensin-converting enzyme 2.
Figure 6 Molecular docking diagram of SARS-CoV-2 with β-sitosterol, kaempferol, and stigmasterol.
SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Discussion
Network pharmacology is commonly used to analyze
the potential targets of TCM in COVID-19. A previous
study corroborated that the components of Huoxiang
Zhengqi Oral Liquid could be combined with ACE2
binding to prostaglandin endoperoxide synthase 2, heat
shock protein 90 AB1, and calmodulin-regulated
spectrin-associated protein 2 to modulate multiple
signaling pathways, thereby exerting a preventive or
therapeutic effect on COVID-19 [35]. Wang et al.
indicated that the active compounds of Huanglian
Jiedu decoction could bind novel coronavirus 3CL
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hydrolase on a target [36], such as prostaglandin
endoperoxide synthase 2, heat shock protein 90 AA1,
and estrogen receptor 1, which probably had an
antiviral effect on COVID-19. Likewise, the main
active components of Qing-Fei-Pai-Du decoction in
the treatment of COVID-19 could regulate targets (e.g.,
MAPK1, MAPK3, MAPK8, MAPK14, and IL6) and
pathways (e.g., TNF and nuclear factor kappa-B
signaling pathways), thereby inhibiting inflammatory
reaction, regulating immune function, reducing lung
injury, and protecting nerve function [37].
Currently, according to the clinical investigation,
patients with COVID-19 develop an excessive
inflammatory response, known as cytokine storm [38,
39]. High levels of cytokines and inflammatory
chemokines can overactivate the immune response
against viral infections and cause extensive
immunopathological damage in vital organs, such as
the heart, lung, and kidney [40]. Our results showed
that MAPK1, IL-6, TNF, CCL2, and MAPK3 might be
the potential targets of CLD in COVID-19. MAPKs
are essential transmitters of signals from the cell
surface to the nucleus, which regulate many
physiological activities, such as inflammation,
apoptosis, oncogenesis, invasion, and metastasis of
tumor cells [41]. MAPK signaling pathway also plays
an essential role in the inflammatory response, which
can be activated by some pro-inflammatory factors,
such as TNF-α and IL family (e.g., IL-1 and IL-6),
thereby aggravating the inflammatory response [42].
GO and KEGG analyses revealed that COVID-19
treatment by CLD involved a variety of BPs, CCs, and
MFs. Meanwhile, the potential targets of CLD in
COVID-19 were significantly enriched in multiple
pathways, including IL-17 signaling pathway, Th17
cell differentiation, TNF signaling pathway, and HIF-1
signaling pathway, indicating that CLD may exhibit
significant immunoregulatory effects in COVID-19
treatment. HIF-1, as a hypoxic signaling transcription
factor, regulates the occurrence and development of
immune inflammation in dendritic cells, macrophages,
and T cells by regulating the expression of
metabolization-related genes, thereby regulating the
expression of immune-related genes and proteins and
maturation and differentiation of related cells [43].
CCL can specifically promote chemotaxis and
activation of eosinophils, leading to an inflammatory
response [44]. Th17 secretes various effectors, such as
IL-17, IL-6, and TNF-α, and IL-17 mediates the
inflammatory response by inducing chemokines and
various pro-inflammatory cytokines, such as IL-6 and
TNF-α [45].
Following molecular docking, the active
components in CLD, including beta-sitosterol,
kaempferol, and stigmasterol, showed high binding
affinity with both S protein of SARS-CoV-2 and
ACE2, indicating that these compounds may directly
inhibit SARS-CoV-2 infection. Interestingly,
beta-sitosterol, kaempferol, and stigmasterol showed
higher binding affinity to S protein than arbidol,
kyprolis, and remdesivir and showed higher binding
affinity to ACE2 than arbidol and darunavir.
Conclusion
This study indicates that modulating the inflammatory
response can be the potential mechanisms of CLD in
COVID-19. Besides, beta-sitosterol, kaempferol, and
stigmasterol can be the key compounds that exert
antiviral effects against SARS-CoV-2. Our prediction
also provides the research fields to further study the
mechanisms of CLD in SARS-CoV-2 infection in the
future.
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