This document reviews several herbal and dietary supplement ingredients that have been implicated in causing liver injury. It discusses challenges in diagnosing liver injury from supplements and establishing causality. It then focuses on specific ingredients that have demonstrated hepatotoxic potential, including black cohosh, ephedrine, green tea extract, Garcinia cambogia, kava kava, saw palmetto, senna glycosides, skullcap, usnic acid, and noni juice. For each ingredient, it summarizes reported uses, predominant injury patterns, mechanisms of injury where known, and case reports associating use with liver damage. It concludes that recognition of potentially hepatotoxic ingredients in supplements consumed can help clinicians identify possible causal relationships for liver injury
Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. Get For More Info Visit Us http://www.jcehapatology.com
Effect of aqueous extract of phaseolus vulgaris l. (red kidney beans) on allo...IJSIT Editor
Aqueous extract of Phaseolus Vulgaris L. (Red Kidney Beans) was investigated for its effects in
alloxan induced-diabetic rats. Twenty four albino rats were randomly allocated into four groups (A-D) of six
rats each such that group A (diabetes control) received 0.5 mL distilled water, group B (diabetes) received
400 mg/kg bwt of extract, group C (normal control) received 0.5 mL of distilled water while group D (normal)
received 400 mg/kg bwt of extract, all extract were orally administered once daily for 14 days. Diabetes was
induced in groups A&B by single interperitonial injection of 150 mg/kg alloxan monohydrate. Phytochemical
screening indicated the presence of alkaloids, balsam, flavonoids, saponins, tannins, cyanogenic glycosides,
terpenes and steroids. The hypoglyceamic potential of Phasoelus vulgaris L. was expressed in diabetes
treated rats. Blood glucose, total protein, albumin and cholesterol levels of the diabetes treated rats and
normal treated rats were not significantly (p>0.05) altered when compared with the control rats. However,
these values were significantly (p<0.05)><0.05)>0.05) effects on PCV and Hb in all groups when compared to the normal control. The study showed that
the aqueous extract of Phasoelus vulgaris L. leaves possess hypoglycaemic, antidiabetic properties and
ameliorating the high levels of marker enzymes observed in diabetes untreated rats.
Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. Get For More Info Visit Us http://www.jcehapatology.com
Effect of aqueous extract of phaseolus vulgaris l. (red kidney beans) on allo...IJSIT Editor
Aqueous extract of Phaseolus Vulgaris L. (Red Kidney Beans) was investigated for its effects in
alloxan induced-diabetic rats. Twenty four albino rats were randomly allocated into four groups (A-D) of six
rats each such that group A (diabetes control) received 0.5 mL distilled water, group B (diabetes) received
400 mg/kg bwt of extract, group C (normal control) received 0.5 mL of distilled water while group D (normal)
received 400 mg/kg bwt of extract, all extract were orally administered once daily for 14 days. Diabetes was
induced in groups A&B by single interperitonial injection of 150 mg/kg alloxan monohydrate. Phytochemical
screening indicated the presence of alkaloids, balsam, flavonoids, saponins, tannins, cyanogenic glycosides,
terpenes and steroids. The hypoglyceamic potential of Phasoelus vulgaris L. was expressed in diabetes
treated rats. Blood glucose, total protein, albumin and cholesterol levels of the diabetes treated rats and
normal treated rats were not significantly (p>0.05) altered when compared with the control rats. However,
these values were significantly (p<0.05)><0.05)>0.05) effects on PCV and Hb in all groups when compared to the normal control. The study showed that
the aqueous extract of Phasoelus vulgaris L. leaves possess hypoglycaemic, antidiabetic properties and
ameliorating the high levels of marker enzymes observed in diabetes untreated rats.
Drug induced hepatotoxicity and its regulatory implicationsChander K Negi
Drug induced hepatotoxicity
Hepatotoxicity implies chemical-driven liver damage. Liver injury may be produced by a large variety of chemical substances The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents Certain medicinal agents, when taken in overdoses & sometimes even when introduced within therapeutic ranges may injure the liver It might not be the drug that cause hepatotoxicity but its metabolite might The herbal drugs and agents can also cause the liver injury
DILI is possible consequence of ingestion of OTC drugs like PCM.
so it require careful clinical knowledge before taking drugs without doctors prescriptions...
The liver plays a key role in detoxifying harmful substances that you may eat, drink, inhale or rub on your skin. Toxic hepatitis is liver inflammation that occurs when your liver is damaged by toxic chemicals, drugs or certain poisonous mushrooms.
Creative Enzymes is a world-wide provider of the best enzyme products. We now offer medical enzymes for pharmaceutical and diagnostic uses. In contrast to the industrial uses, enzymes of therapeutic uses are requested in relatively lower amounts but at a very high degree of purity and specificity. We have the capability to assure high-quality enzyme products based on our advanced equipment and professional techniques. In the past few years, the reliability of our products has been approved by thousands of customers and scientists. Specialized in the medical industry, the various kinds of enzyme products of Creative Enzymes will support your research in multiple areas.
A Thesis Submitted to the College of Medicine and the Committee of Postgraduate Studies of the University of Al-Mustansiriya in Partial Fulfillment of the Requirements for the Degree of Master of Science in Pharmacology
Antihyperglycemic and Anti-hyperlipidemic Effect of Herbamed, A Herbal Formul...CrimsonPublishersIOD
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia and its occurrence is increasing fast in most of the countries. Herbal medicine derived from plant extracts have been utilized increasingly for the treatment of various disorders like diabetes mellitus. The present study was designed to evaluate the anti diabetic activity of ‘Herbamed’, a herbal formulation composed of Vernonia amygdalina, Ocimum gratissimum, Zingiber officinale and Allium sativum in alloxan-induced diabetic rats model.
Drug induced hepatotoxicity and its regulatory implicationsChander K Negi
Drug induced hepatotoxicity
Hepatotoxicity implies chemical-driven liver damage. Liver injury may be produced by a large variety of chemical substances The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents Certain medicinal agents, when taken in overdoses & sometimes even when introduced within therapeutic ranges may injure the liver It might not be the drug that cause hepatotoxicity but its metabolite might The herbal drugs and agents can also cause the liver injury
DILI is possible consequence of ingestion of OTC drugs like PCM.
so it require careful clinical knowledge before taking drugs without doctors prescriptions...
The liver plays a key role in detoxifying harmful substances that you may eat, drink, inhale or rub on your skin. Toxic hepatitis is liver inflammation that occurs when your liver is damaged by toxic chemicals, drugs or certain poisonous mushrooms.
Creative Enzymes is a world-wide provider of the best enzyme products. We now offer medical enzymes for pharmaceutical and diagnostic uses. In contrast to the industrial uses, enzymes of therapeutic uses are requested in relatively lower amounts but at a very high degree of purity and specificity. We have the capability to assure high-quality enzyme products based on our advanced equipment and professional techniques. In the past few years, the reliability of our products has been approved by thousands of customers and scientists. Specialized in the medical industry, the various kinds of enzyme products of Creative Enzymes will support your research in multiple areas.
A Thesis Submitted to the College of Medicine and the Committee of Postgraduate Studies of the University of Al-Mustansiriya in Partial Fulfillment of the Requirements for the Degree of Master of Science in Pharmacology
Antihyperglycemic and Anti-hyperlipidemic Effect of Herbamed, A Herbal Formul...CrimsonPublishersIOD
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia and its occurrence is increasing fast in most of the countries. Herbal medicine derived from plant extracts have been utilized increasingly for the treatment of various disorders like diabetes mellitus. The present study was designed to evaluate the anti diabetic activity of ‘Herbamed’, a herbal formulation composed of Vernonia amygdalina, Ocimum gratissimum, Zingiber officinale and Allium sativum in alloxan-induced diabetic rats model.
Researcheson.zebra.fish,their origin,their role in certain experiments and thus used as model.it is used in heart disease, and their cardiovascular disease
Ellen Kamhi PhD RN and Eugene Zampieron ND . All health providers should be aware of the possibility of interactions between pharmaceutical agents and botanical supplements. This is an introduction to a full course on Drug Nutrient Depletions and Herb Drug Interaction. In this intro, we describe drugs that can cause depletions through a variety of biochemical mechanisms. Depletion of nutrients can lead to alterations in physiology leading to side effects, symptoms or other conditions and disease.
We also review significant herb/drug interactions, and provide a review of databases and information relating to this topic.
Crimson Publishers: Dietary Supplements as a Possible Trigger of Autoimmune H...CrimsonGastroenterology
Introduction: Autoimmune hepatitis (AIH) etiology remains unknown, but in genetically predisposed individuals, diverse agents may trigger the disease. Herbal and drug induced AIH have been reported in recent years probable due to the increase in self-medication. More studies are necessary to define if drugs and herbal/dietary supplements unmask and induce AIH or drug-induced hepatitis with autoimmune features.
Purpose: We report an autoimmune hepatitis case possibly induced by herbal/dietary supplements intake.
Case-report: A 55-year-old female presented with a 15-day course of jaundice and increased aminotransferases. Immunologic panel showed antinuclear antibody titer of 1:320 and serum immunoglobulin G (IgG) level approximately 2 times the upper limit of normal. She reported regular daily ingestion of Herbalife® products for 6 months which were discontinued when symptoms began. Laboratory tests worsened despite the fact that patient had stopped supplements usage, and a liver biopsy was performed. Histology was suggestive of both AIH and drug induced liver disease. The patient fulfilled criteria for probable AIH based on the revised criteria for diagnosing autoimmune hepatitis, and improved with prednisolone and azathioprine therapy, with progressive laboratory improvement and symptoms remission.
Discussion: Herbal/dietary supplements induced AIH has been previously reported, but the causality is not yet well established. Worsening of aminotransferases despite supplement suspension, histological findings and favorable response with corticosteroid treatment, supported the hypothesis of AIH induced by the used supplement. This case report aims to demonstrate the possible causality between herbal/dietary supplements and liver injury, including autoimmune hepatitis.
journal club presentation on effect of vindoline on hyperglycemia and liver...NitinKale46
vindoline effectively ameliorated diabetes induced hepatotoxicity by docking oxidative oxidative stress, inflammation and hyperglycemia in type 2 diabetes rat
Comparative Studies of the Aqueous Extracts of OcimumGratissimum, Aloe Vera, ...IOSR Journals
The current orthodox treatment modalities for diabetic mellitus have many setbacks including undesirable side effects and the high cost of long term treatment. The aim of this study was to determine the anti-diabetic effectsand compare some biochemical parameters of four plants; Ocimumgratissimum (OG),Aloe vera (AV), Brassica oleracea(BO) and Ipomoea batatas(IB) on alloxan induced diabetic rats. The preliminary phytochemical screening reveals the presence ofalkaloid, tannin, cardiac glycoside, resin and steroids in all four plants. Diabetic was induced by interperitonial injection of alloxan monohydrate while treatment was done for 21 days. Diabetic rats had significant increased (P˂0.05)cholesterol, triglyceride (TG), Low Density Lipoprotein (LDL) and artherogenic index (AI). Treatment of experimental rats with 150 mg/kg bw. of aqueous extractsof plants significantly decrease (P˂0.05) the levels of cholesterol and LDL in OG and BO treated groups when compare with the control. Computed artherogenic index was significantly reduced (P˂0.05) in AV treated group when compared to the control. Aqueous extracts also significantly (P˂0.05) alter serum concentrations of alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a similar manner with metformin treated group. Result showed that decrease in plasma glucose was in the order IB˃OG˃BO˃AV. All plant extracts possess antidiabetic, anti-hyperlipidemic effects and were able to ameliorate the weight loss observed in diabetic rats
Potential of edible plant in regulation of obesity and metabolic abnormalitie...Vikas Kumar Jain
Oral presentation on “Potential of edible plant in regulation of obesity and metabolic abnormalities” on National seminar (Ghyan Sangam) organized by Swami Vivekanand College of Pharmacy, Indore on 1st Nov. 2017
Phytochemical evaluation and pharmacological screening of Scrophularia hyperc...SriramNagarajan18
Phytochemical evaluation and pharmacological screening of Scrophularia hypercifolia for hepatoprotective, nephroprotective and antihyperglycemic activity in alloxan induced diabetic rats Mehnoor Farheen*, Tayyaba Siddiqua
Therapeutic Roles of Medicinal Herbs for the Treatment of Jaundice and Hepati...ijtsrd
In the developing countries like India, understating of traditional medicine or medicinal plants is very important for the welfare of rural and tribal communities in the treatment of conventional illness. In the last several years the use of medicinal plants has been on rise across the world, including India. The liver diseases like Jaundice, Hepatitis B have been classically treated by several medicinal plants. Clinical treatment of Jaundice patients by the alternative approach of herbal medication is increasing day by day. Healthcare professionals are also advising the use of herbal medicines. The objective of our present work is to give an elaborate idea about jaundice, its occurrence, and the medicines which causes heptotoxicity and what is the present trend in the research of medicinal plants accredited with hepato protective activities. It is very much beneficial in the identification and the development of relevant compounds or medicinal plant products which are valuable in the treatment of Jaundice and Hepatitis B. Pankaj Varshney | Dr. Kailash Bhargava "Therapeutic Roles of Medicinal Herbs for the Treatment of Jaundice and Hepatitis-B" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-6 | Issue-4 , June 2022, URL: https://www.ijtsrd.com/papers/ijtsrd50100.pdf Paper URL: https://www.ijtsrd.com/chemistry/other/50100/therapeutic-roles-of-medicinal-herbs-for-the-treatment-of-jaundice-and-hepatitisb/pankaj-varshney
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1. REVIEW
Liver Injury Due to Herbal and
Dietary Supplements: A Review
of Individual Ingredients
Elizabeth Zheng, M.D., and Victor Navarro, M.D.
Diagnosing liver injury caused by herbal and dietary
supplements (HDS) and establishing causality is challeng-
ing. These topics are discussed and reviewed in an
accompanying article within this current publication. In
this review, we focus on dietary supplement ingredients
that have hepatotoxic potential (Table 1).
Often, it is difficult to identify the culprit ingredient
that is responsible for liver damage among a multitude
of different components within a particular supple-
ment. However, some ingredients have been associ-
ated with hepatotoxicity. We aim to review those
ingredients that have been implicated in liver injury
and, in doing so, give the practitioner a rationale to
implicate a supplement containing them as a cause for
injury.
We highlight the fact that, although these substan-
ces have been implicated in liver injury, the specific
mechanism of injury in many cases has not been fully
clarified. In fact, in rare instances of liver injury, the
underlying mechanism may be idiosyncratic, that is,
unpredictable.
SUSPECTED TOXIC INGREDIENTS IN HERBAL
AND DIETARY SUPPLEMENTS
Black Cohosh
An herbal remedy extracted from the plant Actaea race-
mosa, black cohosh’s uses vary from alleviation of meno-
pausal symptoms to malaria. The mechanism of injury is
unknown, and some reports suggest that liver injury is an
idiosyncratic reaction. However, case reports support an
immune-meditated reaction because patients presented
with high levels of autoantibodies and exhibited a clinical
response to prednisone.1
A review performed by the US
Pharmacopeia did not reveal convincingly unfavorable clin-
ical pharmacokinetic and animal toxicological data. None-
theless, it determined that black cohosh products should
be labeled with a cautionary statement.2
Ephedrine
Ephedra is a genus of plants, of which a commonly
known species is ma huang (Ephedra sinica). The active
component of ma huang is ephedrine, which is a sympa-
thomimetic alkaloid with thermogenic properties.3
Abbreviations: ALF, acute liver failure; ANA, anti-nuclear antibody; ASMA, anti–smooth muscle actin; GTE, green tea extract; HDS,
herbal and dietary supplements.
From the Department of Hepatology, Einstein Medical Center, Philadelphia, PA.
Potential conflict of interest: Nothing to report.
Received 27 October 2015; accepted 8 February 2016
View this article online at wileyonlinelibrary.com
VC 2016 by the American Association for the Study of Liver Diseases
80 | CLINICAL LIVER DISEASE, VOL 7, NO 4, APRIL 2016 An Official Learning Resource of AASLD
2. Traditionally used in Chinese medicine, ephedrine has
commonly been prepared in weight-loss supplements,
resulting in liver injury as suggested by case reports.4
Ephedrine has been a suspected hepatotoxic agent caus-
ing a hepatocellular pattern of injury with massive necro-
sis on histological examination.5,6
Green Tea Extract
Extracted from the plant Camellia sinensis, green tea
extract (GTE) is composed of catechins and flavanols. As
the most abundant form of catechin, epigallocatechin
gallate is thought to be the active component in GTE
and is often touted to have weight-loss benefits. Epigal-
locatechin gallate has also been found to cause signifi-
cant liver injury through mitochondrial damage and
formation of reactive oxygen species.7,8
The toxicity is
dose dependent in animal models.9
Liver injury has also
been linked to the fasting state in dogs and mice.10,11
Case reports featuring liver injury caused by GTE have
been associated with the use of multi-ingredient weight-
loss supplements.12,13
Although it is unknown whether
hepatotoxicity was due to GTE alone or a combination of
multiple ingredients, reports in patients with previous
liver injury thought secondary to GTE revealed repeated
liver injury after inadvertent re-exposure to GTE.
Garcinia Cambogia
A fruit found in Asia and Africa, G. cambogia contains
the active ingredient hydroxycitric acid, which has the
ability to inhibit the conversion of carbohydrates to fat,
as well as alter adipogenesis.14,15
This ingredient is com-
monly found in multi-ingredient weight-loss supplements
such as Hydroxycut, Exilis, and Herbalife. Several case
reports have documented liver injury after use of Hydrox-
ycut, although direct injury due to G. cambogia is diffi-
cult to assess given the multitude of ingredients within
these supplements.16
In laboratory studies, hepatotoxicity
caused by G. cambogia has been linked to hepatic fibro-
sis, inflammation, and oxidative stress.17
TABLE 1. HEPATOTOXIC INGREDIENTS
Hepatotoxic Ingredient
(species name) Common Uses
Predominant Injury
Pattern Comments
Black cohosh (Cimicifuga racemosa,
rhizome of Actaea racemosa)
Menopausal symptoms Unknown,
autoimmune features
Liver damage ranges from transient increases in liver
enzymes to acute liver failure.
Ma huang (Ephedra sinica,
Ephedra sp.)
Weight loss Hepatocellular* Autoimmune features (ANA and ASMA positive)
observed.
Green tea (Camellia sinensis) Weight loss Hepatocellular Toxicity has been found to be dose dependent and
may be increased in the fasting state.
Garcinia cambogia Weight loss Oxidative stress Associated with hepatic fibrosis and inflammation.
Kava (Piper methysticum) Sedation, anxiolytic Cholestatic* Significant cholestatic hepatitis demonstrated. Liver
damage ranged from transient elevation in liver
enzymes to ALF leading to death and transplant.
Saw palmetto Benign prostatic
hypertension
Hepatocellular Hepatotoxicity rare and self-limited. Idiosyncratic
reaction is possible.
Senna glycosides
(Cassia senna)
Constipation Hepatocellular Damage caused by an active metabolite produced
by intestinal breakdown of the ingredient. Hepato-
toxicity is self-limited and rare.
Skullcap (Scutellaria
baicalensis)
Sedation,
anti-inflammatory
Hepatocellular Injury is self-limited.
Usnic acid Weight loss Hepatocellular
and mixed*
Hepatotoxicity has led to fulminant liver failure.
Noni juice (Morinda
citrifolia)
Seasonal flu, colds, diabetes,
high blood pressure
Hepatocellular Cases of acute liver failure that required liver trans-
plant have been reported.
Abbreviations: ALF, acute liver failure; ANA, anti-nuclear antibody; ASMA, anti–smooth muscle actin.
REVIEW Liver Injury Due to HDS Zheng and Navarro
81 | CLINICAL LIVER DISEASE, VOL 7, NO 4, APRIL 2016 An Official Learning Resource of AASLD
3. Kava Kava
Indigent to the Hawaiian, Polynesian, and Fiji islands, Kava
root, Piper methysticum rhizoma, has traditionally been used
for anxiolytic and antidepressant purposes. Injury has led to
cholestatic hepatitis. In 1 report, of 36 patients studied, 9
patients experienced fulminant liver failure, resulting in 8 sub-
sequent liver transplantations.18
Given that marked eosino-
philic infiltrates were observed in some liver biopsies and
there was lack of dose association with liver injury, the
authors of this series speculate that the mechanism of injury
may be both immunogenic and idiosyncratic.
Saw Palmetto
Saw palmetto is used for urinary hesitancy or urgency
because of benign prostatic hypertension.19
Hepatotoxicity
caused by saw palmetto is rare and self-limited. In the few
published cases, the mechanism of injury was not reported.20
Senna Glycosides
Commonly used for constipation, sennosides are bro-
ken down to an active metabolite, rhein anthrone, which
can cause hepatocellular injury through mitochondrial
damage. Hepatotoxicity is self-limited and rare, although
a recurrence of liver injury after re-exposure has been
observed in one case, giving greater confidence in attri-
bution of injury to this ingredient.21
Skullcap
Often used as a relaxant, Scutellaria baicalensis is a
plant that belongs to the mint family. Clinical reports
have documented use of this herbal remedy for various
reasons from sedation to osteoarthritis.22
A case of hepa-
totoxicity has been documented, but injury was self-
limited after discontinuation.23
Usnic Acid
A common ingredient previously found in weight-loss
products, usnic acid has been shown to uncouple oxida-
tive phosphorylation in mitochondria, thereby increasing
thermogenesis and theoretically possessing antiobesity
properties. Despite its purported weight-loss effects,
usnic acid has been labeled as a direct hepatotoxin, lead-
ing to fulminant liver failure as documented in previously
published case reports.24,25
Noni Juice
Extracted from the Noni fruit, Morinda citrifolia, the
juice has been used for a variety of purposes from the
seasonal flu to diabetes. Cases of acute liver failure, with
one patient requiring liver transplantation, have been
reported.26,27
Despite reported cases of associated liver
injury, the true hepatotoxic potential of M. citrifolia
requires further investigation.
CONCLUSION
Liver injury caused by HDS has become increasingly
recognized by clinical investigators. Initial clinical assess-
ment depends on a careful diagnostic approach and
being aware of the array of potentially hepatotoxic ingre-
dients. We have focused on several common ingredients
that have been implicated in liver injury. Recognition of
these ingredients within HDS consumed by patients with
liver injury should heighten the clinician’s suspicion of a
causal association. In cases in which a mechanism of
injury could not be identified or even surmised from the
clinical reports, one could conjecture idiosyncrasy. How-
ever, a more confident understanding of the mechanism
of injury requires further toxicological study.
CORRESPONDENCE
Elizabeth Zheng, M.D., Hepatology, Einstein Medical Center, Philadel-
phia, PA. E-mail: zhengeli@einstein.edu
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82 | CLINICAL LIVER DISEASE, VOL 7, NO 4, APRIL 2016 An Official Learning Resource of AASLD
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Chem Toxicol 2010;48:409-416.
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