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PHCOG RES. REVIEW ARTICLE

Review of clinical studies of Polygonum multiflorum

Thunb. and its isolated bioactive compounds
Guy‑Armel Bounda1, Feng YU1,2
Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, 2Key Laboratory of Drug Quality Control and
1

Pharmacovigilance, China Pharmaceutical University, Ministry of Education, China

Submitted: 09‑02‑2015 Revised: 18‑02‑2015  Published: 02-06-2015

ABSTRACT
Polygonum multiflorum Thunb.  (PMT), officially listed in the Chinese Pharmacopoeia, is
Access this article online
one of the most popular perennial Chinese traditional medicines known as He shou wu in
Website:
China and East Asia, and as Fo‑ti in North America. Mounting pharmacological studies have www.phcogres.com
stressed out its key benefice for the treatment of various diseases and medical conditions DOI: 10.4103/0974-8490.157957
such as liver injury, cancer, diabetes, alopecia, atherosclerosis, and neurodegenerative Quick Response Code:
diseases as well. International databases such as PubMed/Medline, Science citation Index
and Google Scholar were searched for clinical studies recently published on P. multiflorum.
Various clinical studies published articles were retrieved, providing information relevant to
pharmacokinetics‑pharmacodynamics analysis, sleep disorders, dyslipidemia treatment,
and neurodegenerative diseases. This review is an effort to update the clinical picture of
investigations ever carried on PMT and/or its isolated bio‑compounds and to enlighten its
therapeutic assessment.
Key words: Clinical pharmacokinetics, clinical studies, herbal hepatotoxicity, Polygonum
multiflorum Thunb., therapeutic assessment

INTRODUCTION Chinese Pharmacopoeia.[6] Various parts of the plants were

utilized for different medicinal purposes. The leaves [Figure 2a],
Plants, herbs, and ethnobotanicals have been selected root tuber [Figure 2b] and rhizomes [Figure 2c] of this plant
and used empirically as drugs for centuries, initially as have been used as tonic and anti‑aging agents[7‑12] whereas the
traditional preparations then as pure active principles, with stem [Figure 2d] is used to alleviate insomnia and even to have
the knowledge and accumulated practice passing from an antidiabetic therapeutic activity as well.[13‑15]
generation to generation.[1,2] Medicinal plants are plants
containing the substance that are used for therapeutic Laboratory studies and clinical practice have demonstrated
purposes or which are precursors for the synthesis of that PMT possesses various biological and therapeutic
useful drugs.[3] Herbal Medicinal can be categorized into actions, including anti‑tumor, [16,17] antibacterial, [18]
two broad parts. The first one includes complex of mixture anti‑inflammatory,[13] anti‑oxidant,[19‑21] anti‑HIV,[22] liver
containing a wide variety of compounds (e.g.: Infusions, protection,[23,24] nephroprotection,[25] antidiabetic,[15,26]
essential oils, tinctures or extracts), and the second category anti‑alopecia,[27,28] and anti‑atherosclerotic activities.[29,30] It
refers them as pure, chemically define active principles.[4] has been also reported to exert preventive activity against
neurodegenerative diseases,[31‑35] cardiovascular diseases and
Polygonum multiflorum Thunb. (PMT, Polygonaceae family, to reduce hyperlipidemia as well.[36,37]
Figure 1), well known as He shou wu in China and Fo‑ti in
North America,[5] is one of the most popular perennial Chinese The clinical efficacy, as well as the safety of PMT and
traditional medicinal vine‑like herbs, officially listed in the its bioactive products, has attracted much attention
in the recent years; due to the increasing reports of
Address for correspondence: various cases on hepatotoxicity, [38‑42] published
Prof. YU Feng, Department of Clinical Pharmacy, China
Pharmaceutical University, Nanjing, Jiangsu 210009, China.
worldwide. In the present review, the advancements
Key Laboratory of Drug Quality Control and Pharmacovigilance, in thorough investigation of clinical studies and
China Pharmaceutical University, Ministry of Education, Nanjing, pharmacokinetics (PKs)‑pharmacodynamics (PDs) profile
Jiangsu 210009, China. E‑mail: [email protected]
of P. multiflorum are discussed, meanwhile describing the

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Bounda and Yu: Clinical review of Polygonum multiflorum Thunb

clinical features of this particular herbal‑induced liver injury. active ingredient. The multitude of pharmacologically
This report will enlighten the broad understanding on the active compounds obviously increases the likelihood
clinical therapeutic evaluation of PMT or other herbal drug of interactions taking place. Hence, the likelihood of
containing quite the same phytochemical components. herb‑drug interactions is theoretically higher than that
of drug‑drug interactions, if only because synthetic
drugs usually contain single chemical entities.[43] Case
METHODOLOGY reports and clinical studies have highlighted the existence
of a number of clinically important interactions,
An electronic search was performed by searching several
although cause‑and‑effect relationships have not always
databases: PubMed (Medline), Highwire, HerbMed,
been established. Herbs and drugs may interact either
Google Scholar, Scopus, Cochrane Database of Systematic
pharmacokinetically or pharmacodynamically [Figure 3].[44]
Reviews and Cochrane Library using key terms including,
“PMT,” “He shou wu,” “Shou‑Wu‑Pian,” “Shen‑Min,”
To date, a number of in vitro studies have addressed the
“Fo‑Ti,” and “clinical study,” “humans,” “patients,” “case
potential of selected herbal extracts and/or specific
report,” “hepatotoxicity” to identify English‑language
constituents to inhibit or induce drug‑metabolizing enzymes
publications (case reports, case series, prospective study and
or transporters, especially cytochrome P450 (CYP450)
clinical review articles) and abstracts published regarding
isoforms and P‑glycoprotein (P‑pg). However, translation
P. multiflorum and/or its compounds. Furthermore, we of in vitro data in a clinical setting is hard to accomplish,
scanned the references lists of the primary articles to and discrepancies are often observed between predicted
identify the publications not retrieved by electronic outcomes on the basis of the in vitro studies and results of
research. A total of 54 publications were identified, and controlled clinical studies.[45]
the results compiled. They showed 7 articles relevant to
clinical PKs‑PDs analysis, 2 to anti‑inflammatory effect, 2 Several pharmacological and clinical studies have been
for dyslipidemia treatment, 2 relevant to sleep disorders, done to investigate the PK‑PD parameters analyzes of
3 for neurodegenerative diseases and 52 patients with PMT and/or its bioactive components. In 2002, some
hepatotoxicity due to P. multiflorum ingestion. The quality Korean scientists conducted a clinical PK study about
of clinical studies on P. multiflorum, the characteristics and rhein; one of the main bioactive of PMT.[46] This research
outcomes of patients reported with herbal hepatotoxicity produced some interesting findings, enlightening that in
and the P. multiflorum claimed pharmaco‑therapeutic values terms of the bioavailability, while the levels in aloe‑emodin,
are reviewed and discussed in this paper. emodin, and chrysophanol [Figure 4] in herbal extracts were
much higher than rhein level, only rhein was selectively
CLINICAL PHARMACOKINETICS AND absorbed by the body even if rhein is structurally similar
PHARMACODYNAMICS STUDIES OF POLYGONUM to other anthraquinones.[46] These findings corroborate
the results of another clinical study published a decade
MULTIFLORUM EXTRACTS AND/OR ITS BIOACTIVE
earlier by Krumbiegel and Hu.[47] This phenomenon can
COMPONENTS be explained by one of the three following possibilities.
The first one is that rhein are formed when sennosides
Herbal medicines are mixtures of more than one

a b

c d
Figure 2: Photos of (a) leaves, (b) tuber roots, (c) underground
Figure 1: Polygonum multiflorum Thunb rhizomes and (d) stem from Polygonum multiflorum Thunb

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(e.g.: Sennoside A, Figure 5) are decomposed by bacteria acute toxicity[39,56‑60] of PMT and/or its major bioactive
in the intestines,[48] but the time courses of plasma rhein compounds are all well documented. P‑gp‑based drug
concentrations render this possibility highly improbable. interactions are a major concern in the clinic and in
The second possibility is that sennosides are metabolized preclinical drug development, especially with respect to
by intestinal bacteria into anthrones [Figure 6], and the the intestinal absorption of drugs and distribution of
sulfoconjugation or glucoronidation occurs leading to drugs across the liver, kidney, intestine and blood‑brain
the excretion of the substance through urine.[46] The third barrier.[61] Despite the widespread use of herbal medicines,
possibility stressed out the fact that rhein can be easily documented herb‑drug interactions are spare. However,
bio‑transformed from aloe‑emodin.[47,49] Furthermore, studies on common herbs indicate that significant
in another clinical investigation, the high bioavailability herb‑drug interactions exists.[62] Several commonly used
of rhein was assessed using the routes of administration traditional Chinese medicine (TCM) have been reported to
as comparative key of the research. The findings interact with P‑gp. For example, St. John’s wort was found
suggested that after a single dose of herbal extract, the to increase the duodenal P‑gp expression by 1.4‑fold in
oral bioavailability of rhein was significantly higher healthy volunteers after multiple oral administrations. It
than its rectal bioavailability.[50] By analysis of the route
administration, the absorption of weak acids such as rhein
may be optimal in the acidic environment of the stomach,
whereas their absorption might be unfavorable in the
relatively alkaline situation of the small intestine. Retention
enema therapy requires multiple, higher daily doses due to
poor bioavailability if the same plasma rhein concentration
as oral therapy is to be achieved.[50]

Herbal medicines constituents may affect the function

of the drug‑metabolizing enzymes by inhibiting through
different, yet not completely disclosed mechanisms, the
catalytic activity of specific enzymes, or they may simply
Compound R1 R2
compete for binding. In either case, increase in oral
Aloe‑emodin H CH2OH
bioavailability and/or reduction of hepatic clearance of
Chrysophanol H CH3
the affected drugs are expected to occur, thus leading to Danthron H H
an increase in the plasma drug levels, which may expose Emodin OH CH3
the patient to a serious risk of adverse drug toxicity.[45] Physcion OCH3 CH3
The drug transporters and drug‑metabolizing enzymes Rhein H COOH
involved in the in  vivo process, the modulatory effects Figure 4: Chemical structures of aloe-emodin, chrysophanol, danthron,
on both P‑pg [51‑53] and CYP450 isoenzymes[54,55] and the emodin, physcion and rhein

Figure 3: Schematic representation of the physiologic processes determining drug disposition in the human body and the relationship of
pharmacokinetics and pharmacodynamics to these processes (A: Administration, D: Distribution, M: Metabolism, E: Excretion)

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was also reported that St. John’s wort could result in an their expression appear to be induced by various herbal
18% decrease of digoxin exposure after a single oral dose medicines and/or dietary constituents.[67] The genotype and
of digoxin (0.5 mg).[53,63] Li et al. investigated the inhibitory the allelic frequencies of CYP1A2 were evaluated in Chinese
effect of PMT constituents on P‑pg mediated the digoxin patients with acute liver injury induced by P. multiflorum in
transport in MDR1‑MDCKII cells. The herbal constituents order to investigate CYP1A2 allele polymorphism association
tested were trans‑Resveratrol [Figure 7], 2,3,5,4’‑tetra with the hepatotoxicity from PMT.[55] The findings revealed
hydroxylstilbene‑2‑O‑β‑D‑glucoside (TSG, Figure 8), that the frequency of the CYP1A2 * 1C mutation in Chinese
emodin, chrysophanol, aloe‑emodin, and physcion. patients with P. multiflorum‑induced acute liver injury differed
Among the various constituents of P. multiflorum tested, significantly from that in healthy Chinese people, indicating
emodin was significantly the strongest inhibitor of P‑gp that CYP1A2 * 1C is probably related to metabolism of
(IC50 = 9.42 μM) in MDR1‑MDCKII and Caco‑2 cells.[53] PMT, which is, followed by acute liver injury.[55] Moreover,
Furthermore, clinical study findings enlightened emodin despite the structural similarity and/or identical molecular
to be found to possess the strongest promising effect for weight of various herbal constituents, emodin significant
overcoming P‑gp mediated steroid resistance by inhibiting inhibited CYP3A4/5 activity.[53] Considering P. multiflorum
the P‑gp efflux function.[51]
and/or its constituents as relative toxic compound, potential
Genetic polymorphisms in the CYP450 enzyme also drug‑herb/herb‑herb interactions based on CYP and
contribute to differences in an individual’s ability to metabolize P‑gp should be taken into account when using this herbal
herbal medicines. The use of concurrent medications that medicine in the clinic. By fully appreciating the nature of
either inhibit or induce one or more isoforms, which may PKs, PDs principles, and drug‑herb interactions, healthcare
result in significant changes in the rate of drug clearance, professionals can drastically reduce unwanted side effects
is one of the major reason for altered CYP450 activity.[44,64] and at the same time enhance the therapeutic efficacy and
CYP450 1A2 (CYP1A2) and CYP450 3A4 (CYP3A4) are usefulness of herbal medicines.
involved in the metabolism of xenobiotic in the body,[65,66]

Figure 6: Chemical structure of anthrones

Figure 5: Chemical structure of sennoside A

Figure 7: Chemical structure of trans-resveratrol Figure 8: 2,3,5,4’-tetrahydroxylstilbene-2-O-β-D-glucoside

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CLINICAL STUDIES DONE ON POLYGONUM in vitro studies have demonstrated that anti‑inflammatory
MULTIFLORUM AND/OR ITS BIOACTIVE effects of PMT and/or its bioactive constituents occur
by inhibition of the expression of pro‑inflammatory
COMPOUNDS
signaling factors such as nuclear factor‑κB, tumor necrosis
In general, sound scientific evidence is lacking to support factor‑α, inducible nitric oxide synthase, cyclooxygenase‑2,
the use of many of the herbs currently marketed. chemokines (e.g.,: CCL2) and cytokines (e.g.: Interleukin‑1
A number of herbal products rely on anecdotal beta). [13,52,74,77] P. multiflorum was significantly tested
evidence to support their use. Many of the clinical for the treatment of the localized neurodermatitis by
trials in the literature are of limited quality owing to plum‑blossom needle taping in a clinical study that
small sample sizes, improper randomization, and/or enrolled 141 patients.[78] Moreover, STD07 (Physcion)
the lack of adequate controls. Large‑scale, randomized, developed by Sun Tem Phytotech for the treatment
controlled trials have not been undertaken by the herbal of inflammatory bowel diseases, was evaluated in a
industry owing to the fact that herbs are not patentable, randomized, double‑blind, single‑centered and placebo
and the potential of economic gain from positive controlled study in Asian healthy volunteers.[79] The
study results is limited. A number of researchers and authors found that up to 250 mg/day orally for 14 days;
organizations (e.g. Cochrane collaboration) have attempted STD07 was general well tolerated with no clinically
to critically evaluate available study data through systematic meaningful adverse effects in healthy volunteers in this
reviews and meta‑analyses. Many of the analyses have been Phase I clinical trial. Good therapeutic evidences of P.
equivocal.[68] The use of herbal medicines presents unique multilforum and/or its bioactive constituents have been
clinical and pharmacological challenges not encountered shown in these aforementioned clinical studies to be used
with conventional single‑compound medicines. These as anti‑inflammatory agents. However, extensive clinical
medicines are usually complex mixtures of many bioactive research is needed concerning the therapeutic value of this
compounds and conventional “indications and uses” herbal medicine on its anti‑inflammatory activity.
criteria devised for single‑compound entities may not be
Dyslipidemia
applicable in a significant number of ways.[69]
The hepatocytes play important role in the distribution,
Few clinical studies have been conducted to evaluate the biosynthesis, transferring and removal of triglyceride (TG),
traditional therapeutic claims and to study the potential of total cholesterol (TC), low‑density lipoprotein (LDL),
PMT and/or its various bioactive constituents, highlighting high‑density lipoprotein (HDL) and other related
available clinical evidence. lipoproteins.[80] In normal human liver, the mean contents
of TC and TG are 3.9 and 19.5 mg/g wet weight,
Anti‑inflammatory bioactivity respectively. Traditionally, liver fat content >50 mg/g (5%
Inflammation is known to contribute to physiological and by wet weight) is diagnostic of hepatic steatosis. [81]
pathological processes by the activation of the immune Dyslipidemia, defined as any abnormality of serum lipids and
system, local vascular system, and various cells within the lipoproteins, including low levels of HDL‑cholesterol that
damaged tissue.[70] Prolonged inflammation, known as is associated with increased coronary heart diseases (CHD)
chronic inflammation, is caused by a variety of factors, risk, is a substantial contributor to the incidence of
including microbial pathogen infection, physical, chemical, CHD.[37] In developed countries, most dyslipidemias are
and surgical irritation, and/or wounding and it is involved hyperlipidemias; that is, an elevation of lipids in the blood.
in the pathogenesis of various many chronic diseases, This is often due to diet and lifestyle. Prolonged elevation
including inflammatory bowel diseases, rheumatoid of insulin levels can also lead to dyslipidemia. Similarly,
arthritis, sepsis, and cancer.[71‑74] The classical characteristics increased levels of O‑GlcNAc transferase may cause
of inflammation are pain, swelling, edema, redness, and dyslipidemia. Dyslipidemia can be treated with dietary
heat.[75] Accumulating epidemiological, and clinical evidence alterations and medications that affect lipid metabolism via
shows that chronic inflammation is an important risk factor a variety of mechanisms.[82] Being the first‑line therapies
for various human diseases.[76] Therefore, suppressing the for reducing LDL‑C serum levels, statins also have adverse
production of pro‑inflammatory molecules and signaling effects, including muscle myopathy and derangements in
factors is one of the important target pathways in order hepatic function.[83] Fibrates are second‑line drugs that are
to prevent or treat various diseases. used for the treatment of dyslipidemia and reduce serum
TG levels by activating peroxisome proliferator‑activated
Various natural products from TCM have been shown receptor alpha. However, fibrates increase serum creatinine
to safely suppress pro‑inflammatory pathways and concentrations[84] and have been correlated with sudden
control inflammation‑associated disease. In vivo and/or death, pancreatitis, and venous thrombosis.[85]

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Traditional Chinese medicine plays a very important role In the first large‑scale survey done in Taiwan of the use
in the treatment of dyslipidemic patients.[86] An early of Chinese herbal medicines (CHMs) or the treatment
uncontrolled clinical study of 50 hyperlipidemic patients of insomnia in a Chinese population, P. multiflorum
suggested that PMT has lipid‑lowering effect which may was found to be the most commonly prescribed single
be related to its regulatory effect on the genes involved in Chinese herb.[14] Furthermore, among the Chinese herbal
cholesterol synthesis and lipoprotein metabolism.[87] In a very formulas used to treat insomnia, P. multiflorum was found
recent randomized, double‑blind, placebo‑controlled clinical significantly an important constituent of the ingredients.
trial, the therapeutic effect of P. multiflorum in patients with Although Shou‑wu‑teng (P. multiflorum) is often used to treat
dyslipidemia was investigated.[88] The findings concluded insomnia during clinical practice, no clinical research exists
that being a considerable composition of the multiherb in the Western literature verifying its sedative or anxiolytic
formula, P. multiflorum showed marginal beneficial effect effects.[14] Despite limited evidence from currently available
on reducing plasma LDL cholesterol levels in patients with studies, herbal medicines, especially P. multiflorum and/or
dyslipidemia. In order to validate the claimed dyslipidemia its bioactive compounds may have beneficial effects on
therapeutic action of P. multiflorum and/or its bioactive anxiety and insomnia in patients with bipolar disorder.[108]
compounds, further well‑designed clinical studies with
solid evidence are warranted to investigate this mechanism. Anti‑insomniac phytotherapy opens up an exciting aspect
of research which might benefit a large number of patients
Sleep disorders suffering from different degrees of insomnia. Future
Insomnia or sleeplessness is a sleep disorder in which there is research using CHM for sleep disorders requires further
an inability to fall asleep or to stay asleep as long as desired.[89] rigorous studies with improved methodological design, such
It is prevalent in woman and the elderly by 40% more as using an appropriate placebo control, double‑blinding,
common in women than in men.[90,91] Different measures, validated outcome scales, and longer follow‑up periods.[109]
such as pharmacotherapy and behavioral management, are There is a need for more PD and PK studies to examine
applied for insomnia and associated complaints.[92] Current the mechanism of action, dosage regimen, toxicology
insomnia pharmacotherapeutic agents mainly target the and adverse effects, if there are any drug interactions and
γ‑aminobutyric acid (GABA) receptor, melatonin receptor, the epigenetic differences affected between single active
histamine receptor, orexin, and serotonin receptor. GABA constituents versus whole extracts and complex prescriptive
receptor modulators are ordinarily used to manage insomnia, formulas.[109,110] In order to avoid location bias, as nearly all
but they are known to affect sleep maintenance, including these studies are conducted in China, other countries are
residual effects, tolerance, and dependence.[91] An analysis also encouraged further to pursue CHM clinical studies in
of the United States National Health Interview Survey the treatment of sleep disorders.[112]
data from 2002 by Pearson et  al.[133] revealed that of the
17.4% of adults (n = 93 386) reporting insomnia or regular Neurodegenerative disease
sleep disturbance in the preceding month, 4.5% (of that Age is the leading risk factor for acute and chronic
population) used complementary and alternative medicine neurodegenerative diseases such as Parkinson’s
to improve their sleep. disease (PD), stroke, Huntington’s disease (HD),
vascular dementia (VaD) and Alzheimer’s disease (AD),
In an effort to discover new drugs that relieve insomnia etc., As population aging is occurring on a global scale,
symptoms while avoiding side effects, numerous studies the incidence of these diseases is likely to increase
focusing on the neurotransmitter GABA and herbal significantly in the near future.[111] They show common
medicines have been conducted. Several traditional pathology of aggregation and deposition of abnormal
herbal medicines, such as Valeriana officinalis,[93,94] Passiflora protein. For example, deposit of Aβ and tau in AD,[112]
incarnata,[95,96] Matricaria recutita L.,[97,98] Humulus lupulus,[99,100] α‑Synuclein for Parkinson’s disease,[113] huntingtin protein
Ginkgo bibola,[101] Centella asiatica,[102] Rhodiola rosea,[103] Hypericum in HD,[114] transactive response DNA‑binding protein
perforatum,[104] Piper methysticum[105,106] and Zizyphus jujuba[14] 43 in frontotemporal dementia and amyotrophic lateral
have been widely clinically reported to improve sleep and sclerosis.[115] Neurodegenerative diseases usually have
other mental disorders. Moreover, recently Wuling capsule, a the symptoms of loss of orientation, spoken language,
single herb formula from mycelia of precious Xylaria nigripes was comprehension and learning abilities. To date, there is a
investigated for its efficacy and safety, through a multicenter, lack of effective preventive strategies for these disorders.
randomized, double‑blind, placebo‑controlled trail, in Furthermore, treatments are mainly symptomatic and can
Chinese patients with insomnia.[107] The clinical findings at best temporarily slow down disease progression.[111]
claimed that Wuling capsule could considerably improve Moreover, lack of treatment options has led to an increasing
insomnia and in terms of adverse effect, on a‑6 weeks study number of people to use “natural” and herbal medicines
period the drug was well‑tolerated by all the patients. in an attempt to prevent or delay the deleterious effects

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of ageing as longevity and good health have always been and safety are influenced by different opinions, according
desirable goals for humans. to the clinical or traditional experience of various folk
medicines available in each country. [122] The market
Various herbal medicines and/or their bioactive regulation of herbal medicines is not harmonized because
compounds have been found to exert significant there are different regulations in European, Asian and
therapeutic effect in  vitro model of neurodegenerative North American countries, and as a consequence, this lack
diseases. Pharmacological studies of PMT extract of rules gives poor guarantee of clinical safety.[123] Many
claimed that this medicinal plant may be beneficial in herbal products have been shown to cause severe toxicity,
preventing PD[31] and AD.[9] Furthermore, TSG [Figure 8], but, despite the potential toxicity, there is widespread
one of the bioactive compounds purified from its use among eastern and western general population.
roots significantly antagonized age‑related α‑synuclein Information on clinical issues of herbal medicines are
overexpression in the hippocampus of APP transgenic scarcely available and even if they have been reported,
mouse model of AD[116] and possessed neuroprotection in unlike what happens general practitioners may not be fully
the 1‑Methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP) informed since correct use and safety of herbal medicinal
mouse model of Parkinson’s disease.[35] Ginkgo biloba products is not taught by academic institutions in medicine
and Lycopodium serratum (Huperzine A), through various faculties.[124] The current situation requires the knowledge,
randomized, double‑blind, placebo‑controlled, parallel recognition and monitoring of adverse reactions through
and multi‑center clinical trials have been assessed for pharmacovigilance activities.
their clinical efficacy and safety in AD treatment.[117,118]
Their claimed neuroprotective therapeutic activity was Herbal hepatotoxicity or herb‑induced liver injury is rare
significantly expressed on mild AD clinical cases. and represents a bundle of disorders, each characterized by
a specific herb or herbal mixture considered as potentially
Few clinical trials have investigated the potential therapeutic hepatotoxic.[125] Any individual herb with its multiple
activity of PMT in neurodegenerative diseases. Chen et al. chemical constituents may target different liver cell types
observed the clinical effect of PMT extract on AD.[119] The and/or different subcellular structures, causing likely
findings suggested that the scores for the Mini‑Mental different diagnostic markers for potentially hepatotoxic
State Examination and the Ability of Daily Living Scale herbs and injury types with no single marker characteristic
were significantly improved in the treatment group for herbal liver damage.[126] P. multiflorum (Shou‑Wu‑Pian
compared to the Chinese herb control group and the and Shen‑Min have been the most‑well known products),
western medicine control group (P < 0.01). Moreover, in being one of the most famous Chinese herbs to treat
a randomized, Piracetam‑controlled, single‑center clinical several diseases and medical conditions including dizziness
trial, P. multiflorum (Shouwu yizhi capsule) was evaluated with tinnitus, premature greying of hair, lumbago,
as monotherapy for VaD.[120] The authors found that the spermatorrhea, leucorrhea, constipation and even chronic
total clinical effective rate was 71.25% and that the herbal hepatitis B,[38,59,127] has also been ranked in the top five
medicinal had obvious therapeutic effect on VaD, with no of individual herbs or used most frequently in TCM
relative adverse drug reactions. formulations to induce hepatotoxicity.[128] Several cases of
hepatotoxicity due to PMT have been reported in patients
DCB‑AD1 is a new drug derived from PMT and a medical
from Australia, China, Italy, Japan, The Netherlands and
team in Taiwan is proposing a Phase II double‑blind,
Slovakia taking the product for hair loss, chronic prostatitis
randomized, placebo‑controlled and parallel clinical trial
and to boost the immune system.[38‑40,58,60,129]
to assess its efficacy and safety in patients with mild
to moderate AD.[121] We therefore believe that further
The patients had a history of having ingested PMT
high quality clinical studies on PMT and its isolated
in various forms (tea boil with PMT, liquor made of
bio‑compounds, as well as the herbal mixtures resulted, will
PMT, honey‑soaked out with PMT, and the powder of
assess its actual clinical value and could lead to the discovery
dried PMT). However, it raised the issue concerning
of new drugs for effective treatment and prevention of
the form of the intake with the relation to the severity
neurodegenerative diseases.
of hepatotoxicity.[59] The processed roots of PMT have
displayed lower rates of toxicity as reported in animal
CLINICAL CASES OF POLYGONUM experiments.[130] Processing appears to significantly reduce
MULTIFLORUM‑INDUCED HEPATOTOXICITY the amount of chemicals like 2,3,4′5‑tetrahydroxystilbene‑
2‑O‑β‑Dglucoside, but it remains to be determined if this
Herbal medicines are generally sold as food supplements, can explain reduced toxicity in humans. For raw PMT, the
and as a consequence, therapeutic indications, efficacy, toxicity of water decocta appears to be higher than that of

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acetone extract. Meanwhile, the toxicity of acetone extract Pharmacists and technicians, as well as physicians,
of unprocessed PMT is considerably higher than that of dieticians, and other health care providers must become
acetone extract of processed PMT. High‑performance knowledgeable about herbal supplements and prospectively
liquid chromatography analyses and nuclear magnetic seek information regarding their patients’ use of
resonance analysis revealed that the contents of unconventional medicines to avoid adverse consequences.
characteristic compounds in raw PMT were changed after Consumers need to be reminded that herbs are composed
processing: The content of 2,3,4′,5‑tetrahydroxystilbene of chemicals that may, in some cases be toxic, especially if
2‑O‑β‑D‑glucoside was decreased by 55.8%, whereas large quantities are ingested. Furthermore, much developed
the content of anthraquinone emodin was increased countries and scientific societies are encouraged to
by 34.0%.[40,130] Thus, suggesting that processing should conduct clinical studies on P. multiflorum and/or its isolated
reduce the toxicity of P. multiflorum. compounds in order to evaluate their claimed therapeutic
activities.
CONCLUSION
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Source of Support: Nil. Conflict of Interest: None declared.
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