Polygonum Multiflorum Research Articles

Accumulation of the Major Components from Polygoni Multiflori Radix in Liver and Kidney after Its Long-Term Oral Administrations in Rats.

Although Polygoni Multiflori Radix (PMR) has been widely used as a tonic and an anti-aging remedy for centuries, the extensively reported hepatotoxicity and potential kidney toxicity hindered its safe use in clinical practice. To better understand its toxicokinetics, the current study was proposed, aiming to evaluate the biodistributions of the major PMR components including 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG), emodin, emodin-8-O-β-D-glucopyranoside (EMG) and physcion as well as their corresponding glucuronides following bolus and multiple oral administrations of PMR to rats. Male Sprague-Dawley rats received a bolus dose or 21 days of oral administrations of PMR concentrated granules at 4.12 g/kg (equivalent to 20.6 g/kg raw material). Fifteen minutes after bolus dose or the last dose on day 21, rats were sacrificed and the blood, liver, and kidney were collected for the concentration determination of both parent form and glucuronides of TSG, emodin, EMG, and physcion by HPLC-MS/MS. Among all the tested analytes, TSG, EMG, EMG glucuronides in liver and TSG, EMG, as well as all the glucuronides of these analytes in the kidney demonstrated the most significant accumulation after multiple doses. Moreover, the levels of the parent analytes were all significantly higher in liver and kidney in comparison to their plasma levels. Strong tissue binding of all four analytes and accumulation of TSG, EMG, and EMG glucuronides in the liver and TSG, EMG, as well as the glucuronides of all four analytes in the kidney after multiple dosing of PMR were considered to be associated with its toxicity.

Revive Herbal Capsule: A Review on the Mechanism of Action, Constituent Herbs and Phytochemicals

Revive capsule, also called Kedi Revive capsule is a polyherbal formulation manufactured by Kedi healthcare company limited in Hong Kong, China. The drug is widely used around the globe, especially in Africa and Asia for the treatment of erectile dysfunction or enhancement of libido in men. Each capsule contains 400 mg of the constituent herbs including 80 mg of herb Epimedii, 80mg of Radix ginseng, 40 mg of Cordyceps militaris, 80mg of Tribulus terrestris, 80mg of Radix polygoni multiflori, and 40 mg of Eucommia ulmoides, with its effects exerted four hours after administration via the oral route. The adult man dosage is two capsules (800 mg) to be taken once daily for at least 28 days (before significant improvements may be observed when used to treat erectile dysfunction). Phytochemical analysis of the drug reported the presence of flavonoids, cardiac glycosides, tannins, polyphenols, alkaloids and quinones. Due to its speculated use in the treatment of erectile dysfunction or enhancement of libido, it may be referred to as an herbal phosphodiesterase type-5 inhibitor, that acts by selectively inhibiting the enzyme phosphodiesterase type-5, and thus enhancing increased arterial blood flow into the penis, which results in penile erection; however, the mechanism of action of this drug may be attributed to the contained phytochemicals. Additionally, due to its increased use, it is highly recommended that further studies be conducted on this drug to ascertain its effects on some biochemical components and vital organs of the body.

Herb-Induced Liver Injury Related to Reynoutria multiflora (Thunb.) Moldenke: Risk Factors, Molecular and Mechanistic Specifics.

Herbal medicine is widely used in Asia as well as the west. Hepatotoxicity is one of the most severe side effects of herbal medicine which is an increasing concern around the world. Reynoutria multiflora (Thunb.) Moldenke (Polygonum multiflorum Thunb., PM) is the most common herb that can cause herb-induced liver injury (HILI). The recent scientific and technological advancements in clinical and basic research are paving the way for a better understanding of the molecular aspects of PM-related HILI (PM-HILI). This review provides an updated overview of the clinical characteristics, predisposing factors, hepatotoxic components, and molecular mechanisms of PM-HILI. It can also aid in a better understanding of HILI and help in further research on the same.

HERG Channel-Related Cardiotoxicity Assessment of 13 Herbal Medicines

Objectives: As the use of herbal medicinal products (HMPs) increases worldwide, systematic verification of the safety of HMPs is required. The induction of cardiotoxicity is one of the major factors in post-approval withdrawal of medicinal products, and drug-induced cardiotoxicity assessment is emerging as an important step in drug development. In the present study, we evaluated human ether-à-go-go-related gene (hERG) potassium channel-related cardiotoxicity to predict the risk of cardiac arrhythmia in thirteen herbal medicines known to have cardiac toxicity. Methods: We measured the inhibition rate of hERG potassium channel activity of 13 medicinal herbal extracts in hERG-expressing HEK 293 cells using an automated patch-clamping system. Quinidine was used as a positive control for inhibition of hERG activity. Results: Extracts of Evodiae Fructus, Strychni Semen, and Corydalis Tuber potently inhibited the activity of hERG, and IC<sub>50</sub> values were 3.158, 19.87, and 41.26 <i>μ</i>g/mL, respectively. Cnidi Fructus, Ephedra Herba, Lithospermi Radix, Polygoni Multiflori Radix, Visci Ramulus et Folium, Asiasari Radix et Rhizoma, and Scolopendra weakly inhibited hERG activity, and the IC<sub>50</sub> value for each herbal medicine was more than 400 <i>μ</i>g/mL. Aconiti Kusnezoffii Tuber and two types of Aconiti Lateralis Radix Preparata (Po and Yeom) had weak inhibitory activity against hERG, and the IC<sub>50</sub> values were more than 700 <i>μ</i>g/mL. The IC<sub>50</sub> value of quinidine against hERG was 1.021 <i>μ</i>M. Conclusion: Evodiae Fructus, Strychni Semen, and Corydalis Tuber acted as potent inhibitors against hERG. These herbal medicines may cause cardiac arrhythmia through QT prolongation, so care should be taken when taking them.

Effects of Fallopia multiflora–Andrographis paniculata intercropping model on yield, quality, soil nutrition and rhizosphere microorganisms of F. multiflora

Effects of Fallopia multiflora–Andrographis paniculata intercropping model on yield, quality, soil nutrition and rhizosphere microorganisms of F. multiflora

Update on Pharmacological Activities, Security, and Pharmacokinetics of Rhein.

Rhein, belonging to anthraquinone compounds, is one of the main active components of rhubarb and Polygonum multiflorum. Rhein has a variety of pharmacological effects, such as cardiocerebral protective effect, hepatoprotective effect, nephroprotective effect, anti-inflammation effect, antitumor effect, antidiabetic effect, and others. The mechanism is interrelated and complex, referring to NF-κB, PI3K/Akt/MAPK, p53, mitochondrial-mediated signaling pathway, oxidative stress signaling pathway, and so on. However, to some extent, its clinical application is limited by its poor water solubility and low bioavailability. Even more, rhein has potential liver and kidney toxicity. Therefore, in this paper, the pharmacological effects of rhein and its mechanism, pharmacokinetics, and safety studies were reviewed, in order to provide reference for the development and application of rhein.

An effective strategy for distinguishing the processing degree of Polygonum multiflorum based on the analysis of substance and taste by LC-MS, ICP-OES and electronic tongue

The efficacy of raw and processed products of Polygonum multiflorum (PM) varies greatly. "Nine cycles of steaming and sunning" (NCSS) is recognized as an effective technology in enhancing efficacy and reducing toxicity for PM. In this paper, PM was prepared differently into three groups (including group R, M, and "9"), which represent raw PM, PM processed using the method of Chinese Pharmacopoeia (ChP) and PM processed using traditional NCSS, respectively. The purpose is to establish an effective method to distinguish raw PM from different processed products and highlight the rationality of processing technology. The main organic compounds that could distinguish these three groups of samples were identified by in-depth mining of mass spectral information and various chemometric methods. Level of related metal cations have been quantified and used as another important distinguishing markers. The electronic tongue was utilized to determine the taste traits of aqueous extract from PM. Furthermore, the material basis that caused the difference in taste was discovered according to correlation analysis. In detail, saltiness has the most important contribution associated with the concentrations of K+ and Na+, however, bitterness and astringency were mainly associated with the contents of epicatechin gallate, catechin, procyanidin B1, procyanidin B2 and epicatechin. This study proposed a novel and effective strategy for identification of processing technology of PM. It lays the foundation for clarifying the modern scientific recommendations of processing technology to PM. On the other hand, it also provides a reference for related researches on other traditional Chinese medicine (TCM).

Screening of Quality Markers During the Processing of Reynoutria multiflora Based on the UHPLC-Q-Exactive Plus Orbitrap MS/MS Metabolomic Method.

The root of Reynoutria multiflora (Thunb.) Moldenke (syn: Polygonum multiflorum Thunb.) is a distinguished herb that has been popularly used in traditional Chinese medicine. The raw Reynoutria multiflora (RRM) should be processed by steaming before use, and the processing time is not specified in the processing specification. Our previous studies showed that the efficacy and toxicity of processed Reynoutria multiflora (PRM) at different processing times were inconsistent. A comprehensive identification method was established in this study to find a quality marker of raw Reynoutria multiflora (RRM) and processed Reynoutria multiflora (PRM) with different processing times. Metabolomics based on ultra-high-performance liquid chromatography tandem quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive plus orbitrap MS/MS) was used in this study. Using the CD.2 software processed database, multivariate statistical analysis methods coupled with cluster analysis and heatmap were implemented to distinguish between RRMs and PRMs with different processing times. The results showed that RRM and PRMs processed for 4, 8, 12, and 18 h cluster into group 1, and PRM processed for 24 and 32 h into group 2, indicating that it can effectively distinguish between the two groups and twenty potential markers, made the highest contributions to the observed chemical differences between two groups. Among them, tetrahydroxystilbene-O-hexoside-O-galloyl and sucrose can be used to identify PRM processed for 24 h. Therefore, the properties of RRM changed after 24 h of processing, and the quality markers were screened to distinguish RRM and PPM. It can also be used as an important control technology for the processing of RM, which has wide application prospects.

Combination of Polygoni Multiflori Radix Praeparata and Acori Tatarinowii Rhizoma Alleviates Learning and Memory Impairment in Scopolamine-Treated Mice by Regulating Synaptic-Related Proteins.

Polygoni Multiflori Radix Praeparata (ZhiHeShouWu, PMRP) and Acori Tatarinowii Rhizoma (ShiChangPu, ATR) and their traditional combination (PA) are frequently used in traditional Chinese medicine to prevent and treat Alzheimer disease (AD) based on the theory that PMRP tonifies the kidney and ATR dissipates phlegm. However, the components of PA and their mechanisms of action are not known. The present study analyzed the active components of PA, and investigated the protective effect of PA against cognitive impairment induced by scopolamine in mice along with the underlying mechanism.The aqueous extract of PA was analyzed by high-performance liquid chromatography–mass spectrometry (HPLC-MS) and gas chromatography (GC)-MS in order to identify the major components. To evaluate the protective effect of PA against cognitive dysfunction, mice were orally administered PA, PMRP, or ATR for 30 days before treatment with scopolamine. Learning and memory were assessed in mice with the Morris water maze test; neurotransmitter levels in the hippocampus were analyzed by HPLC-MS; and the expression of synapse-related proteins in the hippocampus was detected by western blotting and immunohistochemistry. Eight active compounds in PA and rat plasma were identified by HPLC-MS and GC-MS. Plasma concentrations of 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside, emodin, α-asarone, and asarylaldehyde were increased following PA administration; meanwhile, gallic acid, emodin-8-O-β-d-glucopyranoside, β-asarone, and cis-methyl isoeugenol concentrations were similar in rats treated with PA, PMRP, and ATR. In scopolamine-treated mice, PA increased the concentrations of neurotransmitters in the hippocampus, activated the brain-derived neurotrophic factor (BDNF)/extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) signaling pathway, and increased the expression of p90 ribosomal S6 kinase (p90RSK) and postsynaptic density (PSD)95 proteins. Thus, PA alleviates cognitive deficits by enhancing synaptic-related proteins, suggesting that it has therapeutic potential for the treatment of aging-related diseases such as AD.

Polygonum multiflorum Thunb. Hot Water Extract Reverses High-Fat Diet-Induced Lipid Metabolism of White and Brown Adipose Tissues in Obese Mice.

The purpose of the present study was to determine whether an anti-obesity effect of a Polygonum multiflorum Thunb. hot water extract (PW) was involved in the lipid metabolism of white adipose tissue (WAT) and brown adipose tissue (BAT) in high-fat diet (HFD)-induced C57BL/6N obese mice. Mice freely received a normal diet (NCD) or an HFD for 12 weeks; HFD-fed mice were orally given PW (100 or 300 mg/kg) or garcinia cambogia (GC, 200 mg/kg) once a day. After 12 weeks, PW (300 mg/kg) or GC significantly alleviated adiposity by reducing body weight, WAT weights, and food efficiency ratio. PW (300 mg/kg) improved hyperinsulinemia and enhanced insulin sensitivity. In addition, PW (300 mg/kg) significantly down-regulated expression of carbohydrate-responsive element-binding protein (ChREBP) and diacylglycerol O-acyltransferase 2 (DGAT2) genes in WAT compared with the untreated HFD group. HFD increased BAT gene levels such as adrenoceptor beta 3 (ADRB3), peroxisome proliferator-activated receptor γ (PPARγ), hormone-sensitive lipase (HSL), cluster of differentiation 36 (CD36), fatty acid-binding protein 4 (FABP4), PPARγ coactivator 1-α (PGC-1α), PPARα, and carnitine palmitoyltransferase 1B (CPT1B) compared with the NCD group; however, PW or GC effectively reversed those levels. These findings suggest that the anti-obesity activity of PW was mediated via suppression of lipogenesis in WAT, leading to the normalization of lipid metabolism in BAT.

Investigation of toxicity attenuation mechanism of tetrahydroxy stilbene glucoside in Polygonum multiflorum Thunb. by Ganoderma lucidum

Ethnopharmacological relevanceThe idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. (PM) has attracted great interest, and tetrahydroxy stilbene glucoside (TSG) was the main idiosyncratic hepatotoxicity constituent, but biological detoxification on idiosyncratic hepatotoxicity of PM was not well investigated. Aim of the studyThis study aimed to illustrate biological detoxification mechanism on PM-induced idiosyncratic hepatotoxicity by Ganoderma lucidum (G. lucidum). Materials and methodsG. lucidum was used for biological detoxification of tetrahydroxy stilbene glucoside (TSG)-induced idiosyncratic hepatotoxicity of PM. The TSG consumption and products formation were dynamically determined during transformation using high-performance liquid chromatography coupled with diode-array detection and electrospray ionization tandem mass spectrometry (HPLC-DAD-MSn). The transformation invertases (β-D-glucosidase and lignin peroxidase) were evaluated by using intracellular and extracellular distribution and activity assay. The key functions of lignin peroxidase (LiP) were studied by experiments of adding inhibitors and agonists. The entire TSG transformation process was confirmed in vitro simulated test. The cellular toxicity of TSG and the transformation products was detected by MTT. ResultsA suitable biotransformation system of TSG was established with G. lucidum, then p-hydroxybenzaldehyde and 2,3,5-trihydroxybenzaldehyde can be found as transformation products of TSG. The transformation mechanism involves two extracellular enzymes, β-D-glucosidase and LiP. β-D-glucosidase can remove glycosylation of TSG firstly and then LiP can break the double bond of remaining glycosides. The toxicity of TSG after biotransformation by G. lucidum was attenuated. ConclusionsThis study would reveal a novel biological detoxification method for PM and explain degradation processes of TSG by enzymic methods.

Activation of Adenosine A1 Receptor in Ischemic Stroke: Neuroprotection by Tetrahydroxy Stilbene Glycoside as an Agonist.

Ischemic stroke is the main cause of death/disability, posing a great menace to human health. Though efforts to search for therapeutic drugs are ongoing, few of them have succeeded. Adenosine A1 receptor (A1R) activation could ameliorate ischemic injury, representing a very tempting target for stroke treatment. Tetrahydroxy stilbene glycoside (TSG), a potent antioxidant from the well-known Chinese herb Polygonum multiflorum Thunb., has been reported to have notable neuroprotective activities but the underlying mechanisms are elusive. This study investigated the mechanism of TSG focusing on A1R. TSG markedly decreased mortality, neurological deficit score, cerebral infarct size and brain water content of MCAO rats, and ameliorated the disorders in purine metabolism, energy metabolism and antioxidative defense system. TSG helped the survival of SH-SY5Y cells in OGD/R by alleviating oxidative stress and glutamate release, and by maintaining calcium homeostasis. TSG effects were abolished by A1R antagonist DPCPX. Docking and binding assays confirmed the binding of TSG with A1R. In addition, TSG upregulated the A1R level lowered by MCAO and OGD/R. The downstream signals of A1R activation, ERK1/2, HIF-1α and NF-κB contributed to the neuroprotection of TSG. Moreover, void of “well-known” cardiovascular side effects of classical A1R agonists, TSG showcased its great potential for stroke treatment.

Fingerprinting and Determination of Hepatotoxic Constituents in Polygoni Multiflori Radix Praeparata of Different Producing Places by HPLC.

Polygoni Multiflori Radix Praeparata (PMRP) is used as Chinese herbal medicine with long history. However, reports about PMRP hepatotoxicity have increased recently, and producing area might be one reason. This article aims to figure out the relationship between producing area and hepatotoxic ingredients in PMRP. HPLC fingerprint for PMRP was established and the contents of gallic acid, trans-stilbene glycoside (TSG), emodin-8-O-β-D-glucoside (EG), emodin and physcion were determined. Clustering heatmap was implemented by TCMNPAS software，and principal component analysis was implemented by SPSS and SIMCA-P software. Hepatotoxic constituents' contents of PMRP from separate producing area were different. PMRP from Guangxi had the highest content of gallic acid, TSG, EG, emodin and physcion, followed by Hubei, Guangdong, Guizhou, Yunnan. PMRP from Henan had the lowest contents of hepatotoxic components. Hepatotoxic components' contents of PMRP in southern were higher than central China. This study carried out a preliminary qualitative and quantitative investigation on the PMRP from different producing places, which provided a basis for safe medication of PMRP.

UHPLC-QQQ-MS/MS assay for the quantification of dianthrones as potential toxic markers of Polygonum multiflorum Thunb: applications for the standardization of traditional Chinese medicines (TCMs) with endogenous toxicity

BackgroundThe raw and processed roots of Polygonum multiflorum Thunb (PM) are commonly used in clinical practice to treat diverse diseases; however, reports of hepatotoxicity induced by Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata (PMRP) have emerged worldwide. Thus, it is necessary for researchers to explore methods to improve quality standards to ensure their quality and treatment effects.MethodsIn the present study, an ultra-high performance liquid chromatography triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) method was optimized and validated for the determination of dianthrones in PMR and PMRP using bianthronyl as the internal standard. Chromatographic separation with a gradient mobile phase [A: acetonitrile and B: water containing 0.1% formic acid (v/v)] at a flow rate of 0.25 mL/min was achieved on an Agilent ZORBAX SB-C18 column (2.1 mm × 50 mm, 1.8 μm). The triple quadrupole mass spectrometer (TQMS) was operated in negative ionization mode with multiple reaction monitoring for the quantitative analysis of six dianthrones. Moreover, compounds 5 and 6 were further evaluated for their cytotoxicity in HepaRG cells by CCK-8 assay.ResultsThe UHPLC-QQQ-MS/MS method was first developed to simultaneously determine six dianthrones in PMR and PMRP, namely, polygonumnolides C1–C4 (1–4), trans-emodin dianthrones (5), and cis-emodin dianthrones (6). The contents of 1–6 in 90 batches of PMR were in the ranges of 0.027–19.04, 0.022–13.86, 0.073–15.53, 0.034–23.35, 0.38–83.67 and 0.29–67.00 µg/g, respectively. The contents of 1–6 in 86 batches of commercial PMRP were in the ranges of 0.020–13.03, 0.051–8.94, 0.022–7.23, 0.030–12.75, 0.098–28.54 and 0.14–27.79 µg/g, respectively. Compounds 1–4 were almost completely eliminated after reasonable processing for 24 h and the contents of compounds 5 and 6 significantly decreased. Additionally, compounds 5 and 6 showed inhibitory activity in HepaRG cells with IC50 values of 10.98 and 15.45 μM, respectively. Furthermore, a systematic five-step strategy to standardize TCMs with endogenous toxicity was proposed for the first time, which involved the establishment of determination methods, the identification of potentially toxic markers, the standardization of processing methods, the development of limit standards and a risk–benefit assessment.ConclusionThe results of the cytotoxicity evaluation of the dianthrones indicated that trans-emodin dianthrones (5) and cis-emodin dianthrones (6) could be selected as toxic markers of PMRP. Taking PMR and PMRP as examples, we hope this study provides insight into the standardization and internationalization of endogenous toxic TCMs, with the main purpose of improving public health by scientifically using TCMs to treat diverse complex diseases in the future.

The Protective Effect of Tetrahydroxystilbene Glucoside on High Glucose-Induced Injury in Human Umbilical Vein Endothelial Cells through the PI3K/Akt/eNOS Pathway and Regulation of Bcl-2/Bax

Endothelial dysfunction plays a central role in the patho­genesis of diabetic vascular complications. 2,3,5,4′-tetra­hydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from the roots of Polygonum multiflorum Thunb, has been shown to have strong antioxidant and antiapoptotic activities. In the present study, we investigated the protective effect of TSG on apoptosis induced by high glucose in human umbilical vein endothelial cells (HUVECs) and the possible mechanisms. Our data demonstrated that TSG significantly reversed the high glucose-induced decrease in cell viability, suppressed high glucose-induced generation of intracellular reactive oxygen species (ROS), the activity of caspase-3, and decreased the percentage of apoptotic cells in a dose-dependent manner. In addition, we found that TSG not only increased the expression of Bcl-2, while decreasing Bax expression, but also activated phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) with subsequent nitric oxide production and ultimately reduced high glucose-induced apoptosis. However, the antiapoptotic effects of TSG were abrogated by pretreatment of the cells with PI3K inhibitor (LY294002) or eNOS inhibitor NG-L-nitro-arginine methyl ester, respectively. These results suggest that TSG inhibits high glucose-induced apoptosis in HUVECs through inhibition of ROS production, activation of the PI3K/Akt/eNOS pathway, and upregulation of the Bcl-2/Bax ratio, and thus may demonstrate significant potential for preventing diabetic cardiovascular complications.

High-Throughput Identification of Organic Compounds from Polygoni Multiflori Radix Praeparata (Zhiheshouwu) by UHPLC-Q-Exactive Orbitrap-MS.

Polygoni Multiflori Radix Praeparata (PMRP), as the processed product of tuberous roots of Polygonum multiflorum Thunb., is one of the most famous traditional Chinese medicines, with a long history. However, in recent years, liver adverse reactions linked to PMRP have been frequently reported. Our work attempted to investigate the chemical constituents of PMRP for clinical research and safe medication. In this study, an effective and rapid method was established to separate and characterize the constituents in PMRP by combining ultra-high performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). Based on the accurate mass measurements for molecular and characteristic fragment ions, a total of 103 compounds, including 24 anthraquinones, 21 stilbenes, 15 phenolic acids, 14 flavones, and 29 other compounds were identified or tentatively characterized. Forty-eight compounds were tentatively characterized from PMRP for the first time, and their fragmentation behaviors were summarized. There were 101 components in PMRP ethanol extract (PMRPE) and 91 components in PMRP water extract (PMRPW). Simultaneously, the peak areas of several potential xenobiotic components were compared in the detection, which showed that PMRPE has a higher content of anthraquinones and stilbenes. The obtained results can be used in pharmacological and toxicological research and provided useful information for further in vitro and in vivo studies.

Comparative Studies on Multi-Component Pharmacokinetics of Polygonum multiflorum Thunb Extract After Oral Administration in Different Rat Models.

The clinical use of Polygonum multiflorum Thunb (PM) has been restricted or banned in many countries, due to its hepatotoxic adverse effects. Its toxicity research has become a hot topic. So far, the pharmacokinetic studies of PM, focusing on prototype compounds such as 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), emodin, and physcion, have been considered the main basis of pharmacodynamic material or of toxic effect. However, pharmacokinetic studies of its phase II metabolites have not yet been reported, mainly because the quantifications of such metabolites are difficult to do without the reference substance. In addition, pharmacokinetic studies on different pathological models treated with PM have also not been reported. On the other hand, toxic effects of PM have been reported in patients diagnosed with different liver pathologies. In the present work, a simultaneous quantitation method for eight prototypes components of PM and their five phase II metabolites has been performed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and used for the pharmacokinetic study of PM in two different liver pathological models in rats (normal, alpha-naphthylisothiocyanate (ANIT), and carbon tetrachloride (CCl4)). The results showed that the main blood-entering components of PM are TSG, emodin, physcion, emodin-8-O-β⁃D⁃glucoside (E-Glu), physcion-8-O-β⁃D⁃glucoside (P-Glu), aloe-emodin, gallic acid, resveratrol and catechin, among which TSG, emodin, and catechin were primary metabolized in phase II, while resveratrol was converted to all phase II metabolites, and the others were metabolized as drug prototypes. Meanwhile, their pharmacokinetic parameters in the different models also exhibited significant differences. For instance, the AUC (0-∞) values of the TSG prototype and its phase II metabolites were higher in the ANIT group, followed by CCl4 group and the normal group, while the AUC (0-∞) values of the emodin prototype and its phase II metabolites were higher in the CCl4 group. To further illustrate the reasons for the pharmacokinetic differences, bilirubin metabolizing enzymes and transporters in the liver were measured, and the correlations with the AUC of the main compounds were analyzed. TSG and aloe-emodin have significant negative correlations with UGT1A1, BSEP, OATP1A4, OCT1, NTCP, MRP2 and MDR1 (p < 0.01). These data suggest that when the expression of metabolic enzymes and transporters in the liver is inhibited, the exposure levels of some components of PM might be promoted in vivo.

Comparative study on the stability/intestinal absorption kinetics of 2,3,5,4′-tetrahydroxy-stilbene-2-O-β-D-glucoside derived from Polygoni Multiflori Radix and its herb pairs

The 2,3,5,4’-tetrahydroxy-stilbene-2-O-β-D-glucoside (THSG) is a main active ingredient of Polygoni Multiflori Radix (PMR). In this study, THSG was found to be a differential chemical composition between PMR and its compatible herb pairs through chemometrics techniques. The effects of the herb pairs Codonopsis Radix-PMR, Astragali Radix-PMR, and Ophiopogonis Radix (OR)-PMR on the stability and absorption behavior of THSG were investigated by simulating the digestive environment in vitro and using an everted gut sac model. The results indicated that the compatible pairs were able to significantly increase the stability of THSG in the gastrointestinal tract and delay the absorption of THSG in the small intestine. OR had the most obvious influence on THSG as the t0.9 values of THSG increased by 14.74- and 6.68-fold in simulated gastric juice and small intestinal fluid, and the apparent permeability coefficient of THSG were 2.07- and 1.97-fold lower for OR-PMR in the ileum and duodenum, respectively. Thus, the compatibility could potentially be used to change the biopharmaceutical properties of THSG. Moreover, the present study established a research method for describing the compatibilities of traditional Chinese medicine based on stability-intestinal absorption, which may provide important reference values for the compatibilities of traditional Chinese medicine.

Distinct metabonomic signatures of Polygoni Multiflori Radix Praeparata against glucolipid metabolic disorders.

Glucolipid metabolic disorders (GLMD) promote a series of major chronic diseases. Polygoni Multilori Radix Preparata (PMRP) has been widely acknowledged in the prevention and treatment of GLMD. We previously reported that water extract (WE) of PMRP and its major bioactive constituents such as polysaccharides (POL) and 2,3,5,4´-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) could alleviate GLMD. The mitochondrial dysfunction is an important mechanism of GLMD, but the underlying mechanisms behind the regulation of mitochondria to alleviate GLMD by WE, POL from PMRP and TSG are still unknown. In this study, we elucidated the effects of WE, POL, and TSG towards regulating the mitochondrial dysfunction and alleviating GLMD using mitochondrial metabonomics. A rat model of GLMD was established by high-sugar and high-fat (HS-HF) diet. Rats were intragastrically given WE, POL, and TSG for 12 weeks. The liver mitochondrial metabolites were analyzed by ultra-high-performance liquid chromatography/mass spectrometry followed by multivariate statistical analysis to identify the differential metabolites and metabolic pathways. The WE, POL, and TSG could significantly restore the level of endogenous metabolites in liver mitochondria toward normal status. In total, sixteen, seven, and fourteen differential metabolites were identified in the liver mitochondrial samples obtained from the WE, GOL, and TSG groups, respectively. These metabolites were found to be mainly involved in glycerol phospholipid, histidine, alanine, aspartic acid, glutamate metabolism, and arginine biosynthesis. PMRP could improve the liver mitochondrial function by regulating the mitochondrial metabolic pathways to alleviate GLMD. Therefore, the application of PMRP might be a promising mitochondrial regulator/nutrient for alleviating GLMD-associated diseases and the mitochondrial metabonomics might provide insights into the evaluation of the efficacies and mechanisms of action of drugs.

THE EFFECT OF POLYPHENOLS FROM POLYGONUM MULTIFLORUM THUNB. ROOT EXTRACT ON THE STORAGE OF GROUND BEEF

The goal of this research is to evaluate the influence of the polyphenols extract of Polygonum multiflorum Thunb. root on the lipid oxidation, chemical properties and sensory characteristics of ground beef during frozen storage. Beef was ground in aqueous solutions of polyphenols extract at different concentrations: 830, 415, 277, 208 and 166 mg GAE/L, polyphenols solution/sample ratio is 1/20 (v/w). Then, the ground beef was stored for up to 100 days at -20±2oC. The best oxidation inhibitor for ground beef was at the highest polyphenols concentration of 830 mg GAE/L. All quality parameters (pH, PoV, MDA, color parameter and sensory evaluation) of the treated sample and of the control sample display significant differences during storage period. For this reason, it was concluded that the polyphenols extract of Polygonum multiflorum Thunb. root could be used as an alternative source of natural antioxidant in beef processing.