This document summarizes research on traditional medicine pharmacology from 2019. It covers two main sections: research highlights and representative disease studies. In research highlights, it discusses studies on artemisinin for cancer ferroptosis, rutin for neuroinflammation, ginseng for gut microbiota and obesity, and teas for metabolic disorders. It also discusses novel directions using supramolecular chemistry. In disease studies, it notes many investigations into herbal compounds for cancer treatment involved mechanisms like tubulin binding. It also mentions studies of traditional medicines for cardiovascular, cerebrovascular, and metabolic diseases as well as inflammation and infection.

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TMR | March 2020 | vol. 5 | no. 2 | 74
doi: 10.12032/TMR20200214163
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Annual advances of integrative pharmacology in 2019
Ke-Wu Zeng1*
, Ming-Yao Gu2*
1
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191,
China; 2
Department of Cell Biology and Medical Genetics, School of Basic Medical Sciences, Shenzhen University Health
Science Center, Shenzhen 51801, China.
*Corresponding to: Ke-Wu Zeng. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical
Sciences, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing 100191, China. E-mail: ZKW@bjmu.edu.cn;
Ming-Yao Gu. No. 1066, Xueyuan Avenue, Nanshan District, Shenzhen University, Shenzhen 51801, China. E-mail:
mingyao@szu.edu.cn.
Highlights
This review covered pharmacological reports of studies conducted during 2019 using traditional medicine
and herb-derived active natural products. Pharmacological reports using active natural products that
targeted cancers were the predominant hot topics. Cardiovascular and cerebrovascular diseases, together
with diabetes and metabolic diseases, are ongoing research areas for traditional medicine. Moreover,
inflammation and infectious disease are also attracting more attention by researchers.
Traditionality
This annual integrative pharmacology review analyzed the pharmacological studies of traditional medicine
in different diseases during 2019, which is able to provide a comprehensive description of the hot spot and
ongoing research areas.

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Abstract
Representative studies concerning the pharmacology of traditional medicine and active herbal products have been
summarized over the past 12 months. This annual integrative pharmacology review encompasses research articles
published during 2019 on the bioactive compounds and extracts used in traditional medicine. Reports highlighting
the pharmacology progress of traditional medicine were specifically introduced, including artemisinin for cancer
cell sensibility and induction to ferroptosis, rutin for neuroinflammation suppression, Ginseng Radix et Rhizoma for
gut microbiota regulation against obesity, green tea and Pu-erh tea for metabolic syndrome, and marine-derived
oligosaccharide (GV-971) from brown algae for anti-dementia. Moreover, novel TCM molecular targets and
pharmacological mechanisms were trialed against different human diseases, including cancers, cardiovascular,
cerebrovascular diseases, diabetes, and metabolic diseases. Notably, herb-derived bioactive products have become
important treatment alternatives for cancer research in 2019. Cardiovascular and cerebrovascular diseases, together
with diabetes and metabolic diseases, are ongoing research areas for traditional medicine. Moreover, inflammation
and infectious disease are also attracting more attention by researchers, which might have been influenced by
seasonal influenza or HIV/Ebola viral infections. Further traditional medicine investigations are required in
neurodegenerative diseases, depression, and mental diseases. Taken together, the findings of the integrative
pharmacology review in 2019 provide a vast number of novel lead compounds or drug candidates for future clinical
agent development and also details a novel series of attractive therapeutic targets and molecular mechanisms for
human diseases.
Keywords: Traditional medicine, Natural product, Pharmacology, Cancer, Inflammation, Infectious diseases
Acknowledgments:
This study was supported by National Key R&D Program of China (2019YFC1708900, 2019YFC1711000).
Abbreviations:
ART: artemisinin; AD: Alzheimer’s disease; NaR: sodium rutin; WaTx: scorpion toxin; TRPA1: transient
receptor potential ankyrin 1; PCA: protocatechuic acid; Aβ: amyloid-beta; PatA: pateamine A; HsFPPS: human
farnesyl pyrophosphate synthase; Gef: gefitinib; Cur: curcumin; mTOR: mammalian target of rapamycin.
Competing interests:
The authors declare that they have no conflict of interest.
Citation:
Ke-Wu Zeng, Ming-Yao Gu. Annual advances of integrative pharmacology in 2019. Traditional Medicine
Research 2020, 5 (2): 74–82.
Executive Editor: Nuo-Xi Pi.
Submitted: 12 February 2020, Accepted: 26 February 2020, Online: 28 February 2020.

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Background
In the almanac for 2019, the representative research
regarding the pharmacology of traditional medicine
over the past 12 months has been systematically
summarized. The results are divided into two sections:
research highlights and representative traditional
medicine studies on different diseases. In the research
highlights section for the pharmacology of traditional
medicine, the antimalarial drugs artemisinin (ART)
and quinine have attracted the most interest from the
scientific community. The proven health benefits of
traditional teas are also a hot topic. Studies of
Alzheimer’s disease (AD) involving traditional
medicine focused on gut microbiota regulation using
Ginseng Radix et Rhizoma and marine-derived
oligosaccharide (GV-971) from brown algae are
emerging treatments. The gut microbiota has recently
been linked to AD, and the potential relationships
between gut microbiota are already associated with a
broad spectrum of human diseases. In representative
traditional medicine studies of different diseases,
reports involving anti-cancer studies still take the top
spot. Moreover, reports on diabetes and metabolic
diseases, or cardiovascular and cerebrovascular
diseases are ongoing. Notably, research reports of
traditional medicines used as therapy for
immunological diseases and infectious diseases
attracted attention during 2019, which likely occurred
because of recent bacterial or influenza virus outbreaks
and HIV or Ebola viral infections. Additionally,
traditional medicine studies against neurodegenerative
diseases, depression, and mental disorders are required
in the future. Collectively, this work provides a broad
annual overview of the trends affecting traditional
medicine pharmacology studies during 2019.
Research highlights involving traditional
medicine pharmacology during 2019
Antimalarial drugs artemisinin and quinine
ART from the herb Artemisia annua Linn. is a famous
antimalarial drug derived from the traditional
medicinal plant Artemisia annua. In addition to the
treatment of malaria, ART has also been reported to
exert multiple pharmacological activities. In this study,
ART, as well as its derivate, were reported to promote
sensibility to ferroptosis in cancer cells, a new form of
programmed cell death. This finding may have helped
to enhance the potential therapeutic effects of
anti-cancer agents involved in ferroptosis-inducing
potency during clinical treatment. Studies concerning
the mechanism of action reveal that an ART derivative
can promote lysosomal degradation of ferritin and
up-regulated cellular free iron levels, resulting in the
cancer cell sensibility to ferroptosis [1]. Moreover,
quinine is a natural antimalarial drug from the bark of
the cinchona tree; however, the underlying antimalarial
mechanism is still controversial. Here, the mechanisms
of action for quinine and a derivative mefloquine were
investigated in depth. The cellular thermal shift assay
was coupled with a mass spectrometry strategy and
applied as a direct cellular target identification for
these two agents in human malaria cases caused by
Plasmodium falciparum (P. falciparum). The results
reveal that P. falciparum purine nucleoside
phosphorylase is a crucial binding target for quinoline
and mefloquine, which provides a potential molecular
explanation for their antimalarial effects and potential
for resistance improvement [2]. Notably, ART-based
combination therapy was also conducted. Furthermore,
an interesting study involving ART-based hybrids
reportedly found that they could overcome drug
resistance to chloroquine in malaria parasites. In this
study, ART-based hybrids were synthetized, including
ART-isoquinoline and ART-quinolone hybrids. These
ART-based hybrids significantly improved chloroquine
resistance and multidrug-resistance in P. falciparum.
Further investigation has suggested that ART-based
hybrids interacted with several cellular target proteins,
including plasmodium falciparumcalcium ATPase 6
and the 40S ribosomal protein, in order to overcome
resistance, suggesting that these hybrids could affect P.
falciparum development [3].
Effects of the flavonoid rutin on neuroinflammation
Rutin is a natural glycoside of flavonoid quercetin
from Herba Hyperici and Ruta graveolens L., which is
involved in multiple biological activities. Recent
studies have revealed that sodium rutin (NaR) is a
promising therapeutic agent for the treatment of
neurodegenerative diseases, including AD, as it can
regulate the microglia-mediated neuroinflammation.
Their results also show that NaR activated microglia to
clean A  by inducing the expression of
phagocytosis-related receptors. NaR also promotes
ATP production for the A clearance energy supply in
the microglia. Since A  clearance is a crucial AD
therapy strategy, NaR may act as a novel agent for AD
by modulating microglia-dependent A clearance and
thereby ameliorating memory deficits [4].
Analgesic effect of scorpion toxin
Scorpion venom from Scorpio has been used in
traditional medicine for many years and has recently
become a research focus. Scorpion venom contains
several types of toxins that regulate ion channel
function. In this study, scorpion toxin (WaTx) was
reported to activate the transient receptor potential
ankyrin 1 (TRPA1) ion channel for the alleviation of
acute and persistent pain. When the mechanism
involved was investigated, it suggested that WaTx
stabilized TRPA1 (responsible for pain
hypersensitivity). These findings indicate that WaTx
can act as a promising therapeutic agent targeting

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TRPA1 to treat clinical-pathological pain [5].
Proven health benefits of traditional tea
Green tea, as a globally popular beverage, contains
various tea polyphenols. Tea catechins and phenolic
acids are metabolized into antioxidant protocatechuic
acid (PCA). In this study, PCA from green tea was
investigated, and a PCA-controlled switch system was
constructed for epigenetic remodeling. By using this
switch system, glucose homeostasis in diabetic mice
and monkeys was restored following oral
administration of the PCA or green tea. This system
was also successfully used for type 1 and type 2
diabetes in the mice and the cynomolgus monkey’s
model, providing a novel therapy strategy for
metabolic disorders [6]. In addition, Pu-erh tea, which
is also known as “black tea,” and originates from
China. Pu-erh tea is post-fermented through a
microbial fermentation process following drying.
Pu-erh tea is reported to exhibit an anti-obesity
function as it lowers the cholesterol level, but the
underlying mechanism has not yet been explicated. As
a key active pigment in Pu-erh tea, theabrownin is
found to alter gut microbiota and increase the ileal
conjugated bile acids, directly resulting in inhibition of
the intestinal farnesoid X receptor-fibroblast growth
factor 15 signaling pathway and reduced hepatic
cholesterol levels. These findings indicate that
intestinal bile-salt hydrolase microbes and farnesoid X
receptor-fibroblast growth factor 15 signaling can act
as crucial therapeutic targets of Pu-erh tea. Thus,
ingestion of this tea can potentially improve metabolic
syndrome [7].
TCM impacts on gut microbiota
Panax ginseng C. A. Mey. has been used in TCM for
centuries, as Ginseng Radix et Rhizoma influences
body weight. However, the precise molecular
mechanism associated with Ginseng Radix et Rhizoma
and obesity is still largely unexplored. In this study, the
effect of Ginseng Radix et Rhizoma extract on the gut
microbiota was investigated to explore the possible
mechanism of action. The results suggest that Ginseng
Radix et Rhizoma extract induces Enterococcus
faecalis (E. faecalis) to produce myristoleic acid,
which activates brown adipose tissue (BAT). Moreover,
acyl-coa thioesterases in E. faecalis are found to exert
biosynthesis to myristoleic acid. These observations
indicate that Ginseng Radix et Rhizoma extract can
markedly promote energy expenditure and reduce
adiposity via BAT activation for the treatment of
obesity and metabolic syndrome [8]. Moreover,
GV-971, a marine brown algae-derived
oligosaccharide with multitargeting mechanisms,
shows cognitive benefit over 36 weeks in patients with
mild to moderate AD. The study of the mechanism of
action reveals that GV-971 returns a gut microbial
profile to normal and lessens the brain immune cell
infiltration and neuroinflammation. Also, an AD mouse
model was administrated with GV-971 and shows
obvious gut microbiota alterations together with a
reduction in amyloid-beta (Aβ) plaques and Th1 cell
numbers in the brain. This study suggests that
microbiome modulation might be an important strategy
for neuroinflammation regulation and AD pathogenesis
[9].
Novel direction for traditional medicine study using
supramolecular chemistry
Hydrogels are key materials used for biomedical
applications. Recently, small-molecule self-assembling
hydrogels have attracted much attention. Several
self-assembly hydrogels derived from natural products
have been synthetized for specific biological activities.
Rhein, an anthraquinone isolated from Rheum
palmatum L., is investigated and reported to directly
self-assemble into hydrogels with three-dimensional
nanofiber networks through noncovalent interactions.
Moreover, rhein hydrogels exert significant
anti-inflammation activity by dephosphorylating IκBα
and inhibiting NF-κB p65 nuclear translocation against
lipopolysaccharide stimulation. These findings suggest
a new direction for a modern medical transformation
of TCM in the supramolecular chemistry field as well
as a new clinical therapy strategy for human
inflammatory diseases [10].
Representative traditional medicine studies
on different human diseases
Cancers
Cancer remains one of the most serious diseases that
threaten human health globally. Therefore, during 2019,
a large number of cancer studies using traditional
medicine as treatments were reported. Withaferin A
from Acnistus arborescens has been found to
covalently bond to cysteine 239 of β-tubulin and
promote degradation, which might inhibit tumor cell
growth by suppressing the cell division [11]. Chaetocin
from the Chaetomium species of fungi inhibits
thioredoxin reductase 1 and subsequently induces
excessive ROS accumulation via inactivation of the
PI3K/AKT pathway, ultimately leading to gastric
cancer cell death [12]. Parthenolide, a kind of
sesquiterpene lactone from the feverfew plant
(Tanacetum parthenium), that covalently modifies
cysteine 427 of the focal adhesion kinase 1, eventually
inhibiting breast cancer cell proliferation, survival, and
motility. Meanwhile, other exocyclic methylene
lactone-containing sesquiterpenes have exhibited
similar activities [13].
A natural product nimbolide derived from the Neem
tree (Azadirachta indica), impairs breast cancer cell
proliferation partly by disrupting ring finger protein
114 substrate recognition, leading to the inhibition of
ubiquitination-dependent degradation of tumor

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suppressors such as p21 [14]. Moreover, microRNAs
have been found to be involved in cancer progression,
and targeting microRNAs by natural agents has opened
avenues for cancer treatment and drug development.
Sanguinarine, one of the most abundant active
ingredients in Sophora alopecuroides L., has been
identified to up-regulate miR-16 expression in
hepatocellular carcinoma cells that suppress tumor
growth via induction of the G0/G1 cell cycle arrest and
apoptosis in a p53-dependent manner [15].
Butylcycloheptyl prodiginine binds to pre-miR-21 and
inhibits dicer-mediated processing, which results in
inhibition of cell proliferation [16].
Significant amounts of research have produced the
synthesis of natural product analogs with the goal of
improving their drug ability while maintaining or
enhancing their biological function. Rapaglutin A is
inspired by the natural products rapamycin and FK506.
Rapaglutin A inhibits glycolysis and ATP biogenesis to
promote AMPK activation, mammalian target
of rapamycin (mTOR) inhibition, and induction of the
cell cycle arrest and apoptosis, eventually blocking
cancer cell growth [17]. Pateamine A (PatA) is isolated
from the New Zealand marine sponge Mycale spp.,
which disturbs eIF4A formation and inhibits
translation initiation. A synthetic derivative of PatA,
des-methyl des-amino PatA blocks mRNA translation,
reduces Mcl-1 protein, and initiated apoptosis in
chronic lymphocytic leukemia cells [18].
Dihydroartemisinin is one of the semi-synthetic
derivatives of artemisinin (from Artemisia annua).
Dihydroartemisinin induces autophagy by regulating
the AMPK/mTOR/p70S6k signaling pathway to
accelerate ferritin degradation for ferroptotic cell death
[19]. Human farnesyl pyrophosphate synthase
(HsFPPS) is a target for bone resorption diseases and
some cancers. HsFPPS is potently inhibited by
bisphosphonates, but due to poor cell penetration and
distribution in the soft tissues. Phenolic diterpene
carnosic acid shows enhanced anti-cancer activities
over the bisphosphonate drug zoledronate using
pancreatic cancer cell lines, and a HsFPPS-dependent
mechanism. Therefore, a series of compounds based on
the carnosic acid are synthesized for pancreatic cancer
by inhibiting HsFPPS [20].
A lot of natural products exude positive therapeutic
effects in cancer therapy; however, the exact
mechanism of action or potential targets require further
investigation. Gambogic acid, with a polyprenylated
xanthone structure, is derived from gamboge resin,
which is exuded from Garcinia hanburyi and Garcinia
morella trees. The anti-cancer mechanism of
Gambogic acid reportedly increases E-cadherin in
non-small cell lung cancer cells by targeting liver
kinase B1 to block the mTOR signaling pathway [21].
Neohesperidin, a flavonoid derived from citrus fruits,
markedly inhibits colorectal tumorigenesis, which may
be mediated by alteration of the gut microbiota.
Furthermore, other citrus flavonoids may share similar
pharmacological properties, indicating a new direction
to develop chemopreventive agents for colorectal
cancer therapy [22]. Neocarzilin A from Streptomyces
carzinostaticus reportedly inhibits cancer cell
migration via irreversible binding to the synaptic
vesicle membrane protein VAT-1, which is a promising
target for the development of anti-cancer drugs via
preventing metastasis [23]. Vioprolides A from
Cystobacter violaceus targets nucleolar protein 14 to
inhibit ribosome biogenesis in the acute lymphoblastic
leukemia cell line, suggesting that Vioprolides A is a
novel chemical tool to be used in the study of
ribosomal processes and drug development [24].
Some natural products have been reported to elicit
synergistic effects in combination with anti-cancer
drugs, which improve the anti-tumor activity or
reduced side effects. Gefitinib (Gef) has been used
clinically due to efficacy against certain cancer cell
types, including non-small cell lung cancer and
esophageal carcinoma. Curcumin (Cur) from Curcuma
longa exerts a broad range of pharmacological
activities. Gef and Cur co-treatment exhibits
synergistic effects on cell viability in oral cancer.
Moreover, γ-polyglutamic acid-coated nanoparticles
loaded with Gef and Cur exhibit higher apoptotic
effects [25]. AlbA-DCA, a conjugate of natural
oleanane triterpenoid saponin albiziabioside A from
Albizia inundata, with PDK inhibitor dichloroacetate
acid, exhibits an excellent synergistic effect for
endometrial, metastatic breast and colorectal cancer
cells [26]. Taken together, these studies demonstrate
evidence that natural products from traditional
medicine used as anti-cancer candidates can potentially
be used as drug targets for future cancer treatments.
Cardiovascular and cerebrovascular diseases
Although the number of studies of cardiovascular and
cerebrovascular diseases in 2019 was limited, there
were some inspiring studies on cerebrovascular
diseases that should be addressed.
2,7,2′-Trihydroxy4,4′7′-trimethoxy-1,1′-biphenanthren
e is a natural product isolated from Cremastra
appendiculata and Liparis nervosa.
2,7,2′-Trihydroxy4,4′7′-trimethoxy-1,1′-biphenanthren
e inhibits the oxygen-glucose deprivation
reoxygenation-induced astrocyte oxidative stress
partially through regulating the nuclear factor erythroid
2-related factor 2/heme oxygenase-1 signaling
pathway [27]. Moreover, geniposide is a natural
product extracted from Gardenia jasminoides and
protected against hypoxic-ischemia-induced brain
injury through the activation of the PI3K/Akt signaling
pathway [28]. These two compounds also exhibit
various activities in other diseases, including
neuroprotective and anti-cancer effects, suggesting a
great opportunity for cardiovascular and
cerebrovascular disease and drug development.

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Inflammation-related diseases
Traditional medicine is an important source for the
treatment of inflammation-related diseases. Nowadays,
there are a lot of natural compounds isolated from
traditional herbs with anti-inflammation effects. For
example, isosibiricin from Murraya exotica L.
inhibites the expression of TNF-α, IL-6, IL-1β, and
IL-18 via up-regulating dopamine D1/2 receptors in
LPS-activated microglial cells [29]. Cymopol and
related natural products from the marine green algae
Cymopolia barbata modulate the host inflammatory
response via activating the anti-oxidative signaling
pathway of nuclear factor erythroid 2-related factor 2
[30]. Moreover, shikonin from Lithospermum
erythrorhizon protects APAP-induced acute liver injury
via modulating the inflammatory response and
oxidative stress [31]. 7-Deoxy-trans-
dihydronarciclasine from Lycoris chejuensis inhibits
the pro-inflammatory factor production and microglial
activation in the LPS-induced models and swedish
mutation amyloid precursor protein transgenic mice
T2576 [32]. Furthermore, gracilin A and derivatives
from Spongionella gracilis exhibits anti-oxidative and
anti-neuroinflammatory properties [33], and gracilin A
congeners are also developed to retain neuroprotective
and immunosuppressive effects at a much earlier
synthetic stage by a simplified method
“pharmacophore-directed retrosynthesis” [34]. These
studies indicate that natural products are a promising
source for the discovery of novel anti-inflammatory
agents and provide pharmacophore data for novel drug
design.
Neurodegenerative diseases
AD is characterized by dementia and cognitive decline,
which threatens human health. Thus, natural products
have been widely investigated for AD. Mangiferin is
extensively distributed in plants and fruits, including
the mango tree, Anemarrhena asphodeloides, Iris
domestica, Gentiana scabra, and Zizyphus
cambodiana [35]. Mangiferin significantly inhibits
lipid peroxidation and decreases Aβ expression to
protect the neurons, resulting in improvements in
learning and memory behaviors [36]. Traditional
Chinese herb Glycyrrhiza uralensis Fisch has been
widely studied in neurodegenerative diseases. Recently,
licoflavonol from Glycyrrhiza uralensis Fisch is found
to prevent the secretion of Aβ, soluble amyloid
precursor protein α and β via increasing BACE1
phosphorylation and degradation [37]. Natural
products macaflavanone C and monachosorin B also
inhibit the γ-secretase activating protein as a potential
therapeutic target of AD [38]. Until now, AD is
considered incurable; thus, taking natural herbs orally
as a preventive measure may protect or delay the onset
of these neurodegenerative diseases.
Diabetes and metabolic diseases
Diabetes mellitus, caused by inadequate insulin
secretion and insulin resistance, is one of the largest
risk factors affecting human health. Natural products
are widely investigated to prevent type 2 diabetes
mellitus. Red alga Rhodomela confervoides-derived
compound 2,2′, 3,3′-tetrabromo-4,4′,5,5′-
tetrahydroxydiphenylmethane is reported to directly
bind to the catalytic pocket of protein tyrosine
phosphatase with an IC50 value of 2.4 μM [39]. Based
on a natural dipetidyl peptidase-4 inhibitor
iso-daphnetin, a series of novel compounds are
discovered that potently inhibit dipetidyl peptidase-4
achieving a more favorable and extended anti-diabetic
efficacy than validated drugs [40]. As for other
metabolic diseases, colletoic acid from Colletotrichum
gloeosporioides is a selective 11β-hydroxysteroid
dehydrogenase type 1 inhibitor and used to block
preadipocyte differentiation for a potential therapeutic
effect on obesity [41]. Another novel natural
compound, antroalbol H from Antrodiella
albocinnamomea, increases glucose uptake in
myotubes and adipocytes through activation of the
LKB1-AMPK pathway at threonine 189 for
hyperglycemia treatment [42]. These studies indicate
that novel metabolism regulation drugs could
potentially be developed from natural compounds in
the future.
Infectious diseases
Natural products have played fundamental roles in
anti-infectious diseases for centuries. Traditional
medicine plant-derived natural products provide a vast
number of effective compounds, particularly
antimicrobial agents, which have shown promising in
vivo and in vitro efficacy against drug-resistant
bacteria [43]. For instance, phytochemical bergenin
from Shorea robusta inhibited mycobacterial growth in
a murine model of Mycobacterium tuberculosis
infection via inducing pro-inflammatory mediators,
including TNF-α, NO, IL-12 [44]. The natural product
agrimophol derivatives from Agrimonia pilosa are
reported to reduce intrabacterial pH with higher
metabolic stability and lower cytotoxicity for
Mycobacterium tuberculosis infection [45]. Moreover,
the natural product eugenol recently has been found to
show anti-Ebola virus effects with EC50 of 1.3 µM [46].
In addition to phytochemicals, there are some
antibiotics derived from Pseudomonas fluorescens
ATCC 39502 and fungus, including β-lactone
antibiotic obafluorin against Gram-positive and
-negative pathogens, as well as the fungal metabolite
apicidin that is biosynthesized by terrestrial strains
against methicillin-resistant Staphylococcus aureus
virulence [47, 48]. Furthermore, the biophenolic
compound C2, a honokiol analog, has been reported to
inhibit bacterial growth via disruption of the bacterial
membrane [49]. Analogs of the natural product
gallinamide A exhibits potent inhibitory activity

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against Plasmodium falciparum cysteine falcipain 2
and 3 [50].
Depression and mental disorders
Mental illness has been investigated utilizing
traditional medicine as treatments; however, further
research is required. The natural product
Andrographolide from Andrographis paniculata
effectively relieves depressive-like behaviors in mice
with chronic unpredictable mild stress, via inducing
autophagy [51]. Moreover, one review concentrates on
the active constituents from TCM antidepressants and
potential mechanisms of action. Chemical structures of
the active ingredients with antidepressant activities in
TCM have been classified and listed in this previous
review. Thus, this review can be considered as a
repository for future investigation [52].
Other diseases
Beyond the above-mentioned diseases, bioactive
compounds from herbal medicine have been reported
to potentially exert therapeutic effects on human acute
or chronic diseases. The tetrapeptides isolated from the
Australian Penicillium fungus have been developed as
bilorphin, which is a potential novel analgesic via
targeting the μ-opioid receptor [53]. Interestingly,
hydrogel combined with carbon dot nanoparticles is
reported to generate ROS, which contributes to
chondrogenic differentiation by regulating the
TGF-β/SMAD and mTOR signaling pathways [54].
Several natural products, such as 25-O-methylalisol F
from Alismaorientale, poricoic acid ZA from Poria
cocos, and salvianolic acid A from salvia miltiorrhiza,
have been investigated to target redox signaling
mediators against kidney diseases [55]. Moreover, the
oleanolic acid derivative HA-19 from Achyranthes
bidentata Blume shows a potential therapeutic effect in
ameliorating muscle atrophy via promoting myoblast
proliferation and terminal differentiation and
down-regulation of the negative growth factor MuRF1
and Atrogin-1 [56]. Licorice isoliquiritigenin-
encapsulated mesoporous silica nanoparticles have
been found to have anti-osteoclast genetic effects by
protecting against inflammatory bone destruction [57].
Furthermore, quercetin alleviates cellular senescence
in Werner syndrome and Hutchinson-Gilford progeria
syndrome by regulating cell proliferation and
restoration of heterochromatin architecture [58].
Loganetin from Loganin enzymatically has been
reported to possess a protective effect in acute kidney
injury by inhibiting TLR4 activity and blocking the
JNK/p38 pathway [59]. Also, curcumin from Curcuma
longa attenuates ischemia-reperfusion injury in the
liver via antioxidant enzymes and decreasing ROS in
the oxidative stress pathway [60]. Natural products
also play an important role in novel drug discovery for
other diseases, and additional efforts will be required
to build a comprehensive database of these natural
compounds.
Conclusion
During the year 2019, several rising star molecules
from traditional medicine, including artemisinin, rutin,
Ginseng Radix et Rhizoma, green tea, Pu-erh tea, and
GV-971, exhibited efficacy as preventive, therapeutic,
or potential treatments for serious illnesses. The merits
of these herbal remedies were highlighted by other
studies, and some of the pharmacological mechanisms
and targets of these TCM bioactive molecules and
extracts were elucidated. Thus, the authors of this
review speculate that the trend toward herbal medicine
will continue in the near future. Importantly,
representative studies of infectious diseases using
traditional medicine as treatments have become more
numerous; this might be due to the rapidly increasing
outbreak of coronavirus pneumonia that began at the
end of 2019. However, studies on neurodegenerative
diseases, depression, and mental disorders are limited
during this study period and require more investigation.
Identification of the pharmacological targets of
traditional medicine also requires further research in
the future.
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