Roots Of Polygonum Multiflorum Research Articles

Evaluating the anticancer potential of Polygonum multiflorum root-derived stilbenes against H2452 malignant pleural mesothelioma cells

A naturally occurring stilbene, resveratrol, shows promising effects in the treatment of malignant pleural mesothelioma (MPM) both as a single agent and in combination with chemotherapeutic drugs. To discover new anticancer agents targeting MPM, stilbene-targeted isolation was performed on the roots of Polygonum multiflorum Thunb., an herbal medicine rich in stilbene compounds. In this study, seven stilbene glycosides (1–7) were isolated, along with four non-stilbenes (8–11), of which compounds 4 and 9–11 have not previously been isolated from this species. Stiquinoside A (1) is a previously undescribed stilbene glycoside, and its structure was elucidated as (E)-2,3,5,4′-tetrahydroxystilbene 2-O-β-d-quinovopyranoside based on 1D and 2D-NMR, HR-ESI-MS, and acid hydrolysis experiments. Compounds 1, 4, 6, and 8 significantly inhibit the growth of MPM cancer cells H2452. These results demonstrate the potential utility of stilbenes in new strategies for the treatment of MPM.

A new flavonostilbene glycoside and four new stilbene derivatives from the roots of Polygonum multiflorum

One new flavonostilbene glycoside, polygonflavanol C (1), two new dimeric stilbene glycosides, multiflorumiside M and multiflorumiside N (2−3), one new diphenyl ethanol glycoside, (R)-2,3,5,4′-tetrahydroxy-diphenylethanol 2-O-β-D-glucopyranoside (4), and one new deoxybenzoin glycoside, 2,4,3′,5′-tetrahydroxy-6-methyl-deoxybenzoin 2-O-β-D-glucopyranoside (5), together with six known ones (6−11), were isolated from the roots of Polygonum multiflorum. Their structures were elucidated by the comprehensive spectroscopic analyses. In addition, compounds 1 and 7 showed significantly in vitro anti-inflammatory activity.

Hepatotoxicity of the Major Anthraquinones Derived From Polygoni Multiflori Radix Based on Bile Acid Homeostasis

Polygoni Multiflori Radix (PMR), the dried root of Polygonum Multiflorum Thunb., has been widely used as traditional Chinese medicines in clinical practice for centuries. However, the frequently reported hepatotoxic adverse effects hindered its safe use in clinical practice. This study aims to explore the hepatotoxic effect of PMR extract and the major PMR derived anthraquinones including emodin, chrysophanol, and physcion in mice and the underlying mechanisms based on bile acid homeostasis. After consecutively treating the ICR mice with PMR extract or individual anthraquinones for 14 or 28 days, the liver function was evaluated by measuring serum enzymes levels and liver histological examination. The compositions of bile acids (BAs) in the bile, liver, and plasma were measured by LC-MS/MS, followed by Principal Component Analysis (PCA) and Partial Least Squares Discriminate Analysis (PLS-DA). Additionally, gene and protein expressions of BA efflux transporters, bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2), were examined to investigate the underlying mechanisms. After 14-day administration, mild inflammatory cell infiltration in the liver was observed in the physcion- and PMR-treated groups, while it was found in all the treated groups after 28-day treatment. Physcion and PMR extract induced hepatic BA accumulation after 14-day treatment, but such accumulation was attenuated after 28-day treatment. Based on the PLS-DA results, physcion- and PMR-treated groups were partially overlapping and both groups showed a clear separation with the control group in the mouse liver. The expression of Bsep and Mrp2 in the physcion- and PMR-treated mouse liver was decreased after 14-day treatment, while the downregulation was abrogated after 28-day treatment. Our study, for the first time, demonstrated that both PMR extract and tested anthraquinones could alter the disposition of either the total or individual BAs in the mouse bile, liver, and plasma via regulating the BA efflux transporters and induce liver injury, which provide a theoretical basis for the quality control and safe use of PMR in practice.

Simultaneously screening multiple UGT1A1 inhibitors from Polygonum multiflorum root using ultrafiltration LC-MS.

Liver injury induced by Polygonum multiflorum root (PMR) is an immediate issue requiring global attention. UDP-glucuronosyltransferase 1A1 (UGT1A1) inhibitors are suspected to additively contribute to the hepatotoxicity of PMR. This study was deliberately designed to simultaneously screen UGT1A1 inhibitors from PMR, and their co-contribution to hepatotoxicity was determined. Using ultrafiltration coupled to LC-MS method, four compounds, namely cis-2,3,5,4'-tetrahydroxystilbene-2-O-β-glucoside, trans-2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside, emodin-8-O-β-d-glucoside, and emodin, were screened, exhibiting the in vitro inhibitory activities against UGT1A1 with IC50 values of 76.23, 18.70, 62.18, and 34.02 μM, respectively. The varying activities of the screened UGT1A1 inhibitors were demonstrated by performing a molecular docking simulation. Finally, zebrafish larvae and mice assays demonstrated that the UGT1A1 inhibitors co-contributed to the hepatotoxicity of PMR. These findings are conducive to understand the role of UGT1A1 inhibitors in PMR-induced hepatotoxicity.

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.

Exploration of components and mechanisms of Polygoni Multiflori Radix-induced hepatotoxicity using siRNA -mediated CYP3A4 or UGT1A1 knockdown liver cells

Ethnopharmacological relevancePolygoni Multiflori Radix, the dried root of Polygonum multiflorum Thunb., and its processed products have been used as restoratives for centuries in China. However, the reports of Polygoni Multiflori Radix-induced liver injury (PMR-ILI) have received wide attention in recent years, and the components and mechanism of PMR-ILI are not completely clear yet. Our previous studies found that the PMR-ILI was related to the down-regulation of some drug metabolism enzymes (DME). Aim of the studyTo explore the effect of the inhibition of CYP3A4 or UGT1A1 on PMR-ILI, screen the relevant hepatotoxic components and unveil its mechanism. MethodsRT-qPCR was used to detect the effects of water extract of Polygoni Multiflori Radix (PMR) and its main components on the mRNA expression of CYP3A4 and UGT1A1 in human hepatic parenchyma cell line L02. High-performance liquid chromatography (HPLC) was employed to detect the content of major components in the PMR. And then, the stable CYP3A4 or UGT1A1 knockdown cells were generated using short hairpin RNAs (shRNA) in L02 and HepaRG cells. Hepatotoxic components were identified by cell viability assay when PMR and its four representative components, 2,3,5,4ʹ-tetrahydroxy stilbene glycoside (TSG), emodin (EM), emodin-8-O-β-D-glucoside (EG), and gallic acid (GA), acted on CYP3A4 or UGT1A1 knockdown cell lines. The PMR-ILI mechanism of oxidative stress injury and apoptosis in L02 and HepaRG cells were detected by flow cytometry. Finally, the network toxicology prediction analysis was employed to excavate the targets of its possible toxic components and the influence on the metabolic pathway. ResultsPMR and EM significantly inhibited the mRNA expression of CYP3A4 and UGT1A1 in L02 cells, while TSG and GA activated the mRNA expression of CYP3A4 and UGT1A1, and EG activated CYP3A4 expression while inhibited UGT1A1 expression. The contents of TSG, EG, EM and GA were 34.93 mg/g, 1.39 mg/g, 0.43 mg/g and 0.44 mg/g, respectively. The CYP3A4 or UGT1A1 knockdown cells were successfully constructed in both L02 and HepaRG cells. Low expression of CYP3A4 or UGT1A1 increased PMR cytotoxicity remarkably. Same as PMR, the toxicity of EM and GA increased in shCYP3A4 and shUGT1A1 cells, which suggested EM and GA may be the main components of hepatotoxicity in PMR. Besides, EM not only inhibited the expression of metabolic enzymes but also reduced the cytotoxicity threshold. EM and GA affected the level of ROS, mitochondrial membrane potential, Ca2+ concentration, and dose-dependent induced hepatocyte apoptosis in L02 and HepaRG cells. The network toxicology analysis showed that PMR-ILI was related to drug metabolism-cytochrome P450, glutathione metabolism, and steroid hormone biosynthesis. ConclusionThe inhibition of mRNA expression of CYP3A4 or UGT1A1 enhanced hepatotoxicity of PMR. EM and GA, especially EM, may be the main hepatotoxic components in PMR. The mechanism of PMR, EM and GA induced hepatotoxicity was proved to be related to elevated levels of ROS, mitochondrial membrane potential, Ca2+ concentration, and induction of apoptosis in liver cells.

The composition differences between small black beans and big black beans from different habitats and its effects on the processing of Polygonum multiflorum.

The roots of Polygonum multiflorum (PM) serve as a classical traditional Chinese medicine (TCM), which has multiple biological activities. However, many cases of hepatotoxicity in PM have been reported in recent years. Processing PM with black beans decoction is one of the typical processing methods to reduce the hepatotoxicity of PM since ancient times. To find potential effective constituents, as well as the optimal variety and origin of black beans for the processing of PM. Based on ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry (UHPLC-Q-Orbitrap-MS) analysis, we measured the contents of the two potential toxic compounds (emodin-8-O-glucoside and torachrysone-O-hexose) in raw PM (R-PM), PM processed with big black beans (B-PM) and PM processed with small black beans (S-PM). The flow cytometry method analysed the effects of different processed products of PM on apoptosis of L02 cells in different drug concentration. Proton nuclear magnetic resonance (1 H-NMR) and UHPLC-Q-Orbitrap-MS together with multivariate statistical analysis were used to systematically analyse the different components between small black beans (Small-BB) and big black beans (Big-BB) from 30 different habitats. The toxicity was ranked from small to large: S-PM < B-PM < R-PM. Processing PM with black beans could significantly decrease the apoptosis rate of L02 cells, especially when the drug concentration is 80 μg/mL. Besides, we find five differential compounds (α-arabinose, α-galactose, proline, isomer of daidzein and isomer of genistein) may be potential active ingredients. In terms of the black beans collected from 30 producing areas, we find that Small-BB from Weifang in Shandong province was optimum to processing PM, followed by Shangqiu in Henan province, Jilin and Liaoning province. The ingredients that affect the processing of PM may be attributed to α-arabinose, α-galactose, proline, isomer of daidzein and isomer of genistein in black beans. When the drug concentration is higher, the effect of reducing the hepatotoxicity of PM is better. Besides, Small-BB was more effective than Big-BB for reducing the toxicity of PM, especially Small-BB from Weifang in Shandong, Shangqiu in Henan province and northeast China.

Advances in Understanding the Metabolites and Metabolomics of Polygonum multiflorum Thunb: A Mini-review.

The roots of Polygonum multiflorum (PM) are a well-known traditional Chinese medicine, widely used to treat a variety of conditions in Southeast Asia, South Korea, Japan and other countries. It is known that Polygoni Multiflori Radix Praeparata (PMRP) may enhance the efficacy and reduce the toxicity of PM. However, reports of adverse reactions, such as hepatotoxicity, caused by PM or PMRP, have continuously appeared around the world, which increased the known risks of the medication and gradually gained the extensive attention of many researchers. The chemical constituents of PM that cause hepatotoxicity have not been distinctly elucidated using the traditional phytochemical screening. Recently, with the rapid development of metabolomics, there has been a growing need to explore the potential hepatotoxic components and mechanisms of PM. The metabolites and metabolomics of PM were searched by the Web of Science, PubMed, Google scholar and some Chinese literature databases. A brief description of metabolites and metabolomics of PM is followed by a discussion on the metabolite- induced toxicity in this review. More than 100 metabolites were tentatively identified and this will contribute to further understanding of the potential hepatotoxic components of PM. Meanwhile, some toxic compounds were identified and could be used as potential toxic markers of PM. This review mainly outlines the metabolites and metabolomics of PM that have been identified in recent years. This study could help to clarify the potential hepatotoxic components and metabolic mechanisms of PM and provide a scientific reference for its safe clinical use in the future.

Multiflorumisides H[sbnd]K, stilbene glucosides isolated from Polygonum multiflorum and their in vitro PTP1B inhibitory activities

A phytochemical study on a 70% EtOH extract of dried roots of Polygonum multiflorum resulted in the isolation of four undescribed stilbene glucosides, namely multiflorumisides HK (1–4). The structures of the natural products were elucidated by 1D and 2D nuclear magnetic resonance (NMR) as well as mass spectroscopy analyses. Among them, multiflorumiside J (3) and multiflorumiside K (4) belong to rare tetramer stilbene glucosides. Moreover, the in vitro inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) were evaluated and the putative biosynthetic pathway was proposed. Notably, compounds 1–4 showed the inhibitory activity against PTP1B with the IC50 values of 1.2, 1.7, 1.5 and 4.6 μm, respectively. Based on the obtained results, stilbene glucosides could be the potential PTP1B inhibitors of P. multiflorum.

Hepatoprotective activity of fresh Polygonum multiflorum against HEP G2 hepatocarcinoma cell proliferation

The modulatory activity of water extracts from fresh roots of Polygonum multiflorum (WRP) on oxidative stress in two liver cell lines was investigated for the first time. WRP increased antioxidant enzyme activities in Clone 9 cells, including catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx). The intracellular glutathione (GSH) level was also increased in the Clone 9 cells owing to antioxidase activity elevating effect by WRP treatment for 24 h. On the other hand, reactive oxygen species (ROS) were generated in abundance upon WRP treatment in Hep G2 cells, resulting in the suppression of cell proliferation. Apoptosis was increased to 78% and 77% after WRP (1000 μg/mL) treatment for 24 and 48 h, respectively. Moreover, WRP stimulated the activation of caspase-8, caspase-9, and ultimately caspase-3. Hep G2 cell growth suppression and caspase induction by WRP were greater than that by emodin-like substances (WRPE), a major active compound. These results indicated that phytochemicals present in extracts of P. multiflorum root act synergistically to promote apoptosis, suggesting the possible use of these extracts for hepatoprotection.

New phenolic constituents obtained from Polygonum multiflorum

ObjectiveTo isolate the phenolic compounds obtained from the dried roots of Polygonum multiflorum and investigate their pharmacological activities. MethodsThe chemical constituents were isolated and purified by combining them with a macroporous resin (DM-8), MCI gel, and Sephadex LH-20 and by performing ODS column chromatography. Their structures were elucidated by 1D and 2D NMR analyses, as well as mass spectrometry. The isolated compounds were evaluated to determine their hepatoprotective and α-glucosidase inhibitory activities in vitro. ResultsTwo phenolic compounds, namely, polygonimitin E (1) and polygonimitin F (2), were isolated from the dried roots of P. multiflorum. Compound 2 (10 µmol/L) only showed moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage. Unfortunately, these two compounds exhibited no α-glucosidase inhibitory activity. ConclusionCompounds 1 and 2 were new compounds. Compound 2 could be one of the potential hepatoprotective constituents of P. multiflorum.

Preparative isolation and purification of 12 main antioxidants from the roots of Polygonum multiflorum Thunb. using high-speed countercurrent chromatography and preparative HPLC guided by 1,1'-diphenyl-2-picrylhydrazyl-HPLC.

A hyphenated strategy by off-line coupling of 1,1'-diphenyl-2-picrylhydrazyl-high-performance liquid chromatography, high-speed countercurrent chromatography, and preparative high-performance liquid chromatography was established to screen and separate antioxidants from ethyl acetate fraction of the roots of Polygonum multiflorum. Under the targeted guidance of 1,1'-diphenyl-2-picrylhydrazyl-high-performance liquid chromatography experiment, 12 compounds were identified as potential antioxidants and readily isolated by high-speed counter-current chromatography and preparative high-performance liquid chromatography. Ultraviolet spectroscopy, mass spectrometry, and 1 H NMR spectroscopy were employed to identify their structures, which were assigned as gallic acid (1, 6.2mg, 98.28%), catechin (2, 8.8mg, 90.69%), epicatechin (3, 4.1mg, 96.71%), polydatin (4, 5.3mg, 94.91%), 2,3,5,4'-tetrahydroxy stilbene-2-Ο-β-D-glucoside (5, 20.2mg, 95.23%), piceatannol (6, 5.3mg, 96.85%), rutin (7, 5.4mg, 97.92%), resveratrol (8, 5.2mg, 96.94%), isorhapontigenin (9, 11.4mg, 94.81%), hyperoside (10, 9.7mg, 98.52%), rhein (11, 4.9mg, 97.46%), and emodin (12, 8.2mg, 95.74%). Notably, compounds 6 and 9 were isolated from Polygonum multiflorum for the first time. In addition, antioxidant activity of compounds 1-12 were evaluated, and compounds 1-8 and 10 exhibited stronger antioxidant activity than ascorbic acid (positive control). These results indicated that the proposed method is a highly efficient strategy to screen and isolate antioxidants from complex natural products.

Stilbenes with Potent Protein Tyrosine Phosphatase-1B Inhibitory Activity from the Roots of Polygonum multiflorum

Seven new stilbene glycosides including three dimers (1-3) and four monomers (4-7) were isolated from the roots of Polygonum multiflorum along with nine previously identified stilbenes (8-16). In addition, two deglucosylated stilbenes, 2a and 3a, were also obtained as new dimeric stilbenes. The structures of the purified phytochemicals were elucidated by interpreting their spectroscopic data (NMR, HRMS, and ECD). To the best of our knowledge, this represents the first isolation of a phenylpropanoid (C6-C3) substituted with a stilbene unit (7) from the Polygonaceae family. In an in vitro enzyme assay with human recombinant protein tyrosine phosphatase-1B (PTP1B), compounds 2-5 showed weak PTP1B inhibition with an IC50 value range of 27.4-37.6 μM, while three deglucosylated stilbenes 2a, 3a, and 8a exhibited IC50 values of 2.1, 1.9, and 12.1 μM, respectively. The inhibition modes and binding mechanism of selected inhibitors (2a and 3a) were investigated using kinetic methods and molecular docking simulations.

Advances in the Study of the Potential Hepatotoxic Components and Mechanism of Polygonum multiflorum.

The roots of Polygonum multiflorum (PM) (He Shou Wu in Chinese) are one of the most commonly used tonic traditional Chinese medicines (TCMs) in China. PM is traditionally valued for its antiaging, liver- and kidney-tonifying, and hair-blackening effects. However, an increasing number of hepatotoxicity cases induced by PM attract the attention of scholars worldwide. Thus far, the potential liver injury compounds and the mechanism are still uncertain. The aim of this review is to provide comprehensive information on the potential hepatotoxic components and mechanism of PM based on the scientific literature. Moreover, perspectives for future investigations of hepatotoxic components are discussed. This study will build a new foundation for further study on the hepatotoxic components and mechanism of PM.

Stilbene Glycoside Oligomers from the Roots of Polygonum multiflorum.

Five new trans-2,3,5,4'-tetrahydroxystilbene 2-O-β-d-glucopyranoside (TSG)-based stilbene glycoside oligomers (1-5) were isolated from the roots of Polygonum multiflorum. Their structures were elucidated by comprehensive spectroscopic analyses and chemical evidences. The absolute configurations of 1, 2, 4, and 5 were established by quantum-chemical electronic circular dichroism (ECD) calculations. Putative biosynthetic pathways of 1-5 were proposed using TSG as the key precursor. In addition, compounds 1 (multiflorumiside H) and 3 (multiflorumiside J) exhibited moderate inhibitory activities against NO production in LPS-stimulated RAW264.7 cells.

Rapid Discovery of the Potential Toxic Compounds in Polygonum multiflorum by UHPLC/Q-Orbitrap-MS-Based Metabolomics and Correlation Analysis.

The dry roots of Polygonum multiflorum (PM), involving both the raw and processed materials, are widely used as the traditional Chinese medicine for treating various diseases in China. Hepatotoxicity has been occasionally reported in patients who consume PM. Unfortunately, no definite criteria are currently available regarding the processing technology of PM for reduction the toxicity. In this work, we aimed to investigate the variations of PM metabolite profiles induced by different processing technologies by UHPLC/Q-Orbitrap-MS and multivariate statistical analysis, and to discover the potential toxic compounds by correlating the cytotoxicity of L02 cell with the contents of metabolites in raw and processed PM samples. We could identify two potential toxic compounds, emodin-8-O-glucoside and torachrysone-O-hexose, which could be selected as the toxic markers to evaluate different processing methods. The results indicated all processed PM samples could decrease the cytotoxicity on L02 cell. The best processing technology for PM process was to steam PM in black soybean decoction (BD-PM) for 24 h.

Integrating Targeted and Untargeted Metabolomics to Investigate the Processing Chemistry of Polygoni Multiflori Radix.

Polygoni Multiflori Radix (PMR, Heshouwu in Chinese), derived from the tuberous roots of Polygonum multiflorum Thunb., is a widely-used Chinese medicinal material. For traditional clinical use, raw PMR (RPMR) is processed by nine cycles of steaming and drying to generate processed PMR (PPMR); RPMR and PPMR have distinct medicinal purposes based on the theory of traditional Chinese medicine. While PMR has been processed for hundreds of years, including the present, the chemistry of that processing has not been well studied. In this study, targeted and untargeted metabolomics analyses using ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) and ultra-performance liquid chromatography-quadrupole/triple quadrupole mass spectrometry (UPLC-QqQ-MS/MS) were integrated to investigate the processing chemistry of PMR. The results demonstrate that processing by nine cycles of steaming and drying qualitatively and quantitatively alters the chemical profile of PMR. Several mechanisms, namely hydrolysis, dehydration, isomerization, and Maillard reaction appear to be involved in the chemical transformation that occurs. The qualitative and quantitative data further suggest that nine cycles might be necessary for the preparation of PPMR, as PPMR that has been processed nine times shows significant differences in its chemical profile.

반응표면 분석법에 의한 표고균사체발효 적하수오 열수 추출조건의 최적화

This study was performed to determine optimal extraction conditions of fermented Polygonum multiflorum root by Lentinula edodes (JMI10079) Pegler mycelials using response surface methodology. The independent factors were extraction temperature (X1: 40–100oC), extraction time (X2: 2–10 hrs.), and the ratio of water to sample (X3: 33–100 mg/mL). Their effects were assessed on dependent variables of the extract properties, which included soluble solid contents (Y1), °Brix of sample extract (Y2), total polyphenol content (Y3), total flavonoid content (Y4), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical cation scavenging activity (Y5) and 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (Y6). The experimental data obtained were fit to a second-order polynomial equation. The optimal extraction conditions for fermented P. multiflorum root were: X1: 91.22°C, X2: 7.72 hrs, and X3: 39.71 mg/mL.

Multiflorumisides A-G, Dimeric Stilbene Glucosides with Rare Coupling Patterns from the Roots of Polygonum multiflorum.

Multiflorumisides A-G (1-7), seven new dimeric stilbene glucosides with two rare coupling patterns, were isolated from the roots of Polygonum multiflorum. The structures of these new dimeric stilbene glucosides were elucidated through comprehensive spectroscopic and chemical analyses. The absolute configurations of 3 and 5-7 were established by comparing their experimental and quantum-chemical ECD data. Putative biosynthetic pathways toward the dimers and their suppressive effects against nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells are also discussed.

Application of HPLC-LTQ Orbitrap MS for metabolic profiles of Polygonum multiflora extract in rats.

The root of Polygonum multiflorum (PM) is an important Chinese herbal medicine for treatment of various diseases. Extensive pharmacological studies have been conducted and demonstrated that it shows a wide range of bioactivities. Meanwhile, a considerable number of hepatotoxicity cases owing to oral administration of PM have been reported and have attracted great attention. However, the limited knowledge regarding the metabolism of PM restricts the deeper studies on its pharmacological/toxicological mechanism and therapeutic material basis. The present study aimed to develop a high-performance liquid chromatography coupled with a linear ion trap-Orbitrap hybrid mass spectrometry method for separation and identification of metabolites in rat urine and plasma after oral administration of PM. Based on the proposed strategy, metabolism profiles of PM in rats were proposed for the first time and 43 metabolites were characterized or tentatively identified. Phase II metabolism, such as glucuronidation and sulfation, are the principal pathways of the main components. These findings will be beneficial to further understanding of the pharmacological mechanism and pharmacodynamic material basis of PM.