Study on the differential hepatotoxicity of raw polygonum multiflorum and polygonum multiflorum praeparata and its mechanism.

BACKGROUND: Polygonum multiflorum (PM), a widely used traditional Chinese medicine herb, is divided into two forms, namely raw polygonum multiflorum (RPM) and polygonum multiflorum praeparata (PMP), according to the processing procedure. Emerging data has revealed the differential hepatotoxicity of RPM and PMP, however, its potential mechanism is still unclear. METHODS: In our study, we investigated the differential hepatotoxicity of RPM and PMP exerted in C57BL/6 mice. First, sera were collected for biochemical analysis and HE staining was applied to examine the morphological alternation of the liver. Then we treated L02 cells with 5 mg / mL of RPM or PMP. The CCK8 and EdU assays were utilized to observe the viability and proliferation of L02 cells. RNA sequencing was performed to explore the expression profile of L02 cells. Western blotting was performed to detect the expression level of ferroptosis-related protein. Flow cytometry was used to evaluate ROS accumulation. RESULTS: In our study, a significant elevation in serum ALT, AST and TBIL levels was investigated in the RMP group, while no significant differences were observed in the PMP group, compared to that of the CON group. HE staining showed punctate necrosis, inflammatory cell infiltration and structural destruction can be observed in the RPM group, which can be significantly attenuated after processing. In addition, we also found RPM could decrease the viability and proliferation capacity of L02 cells, which can be reversed by ferroptosis inhibitor. RNA sequencing data revealed the adverse effect of PM exerted on the liver is closely associated with ferroptosis. Western blotting assay uncovered the protein level of GPX4, HO-1 and FTL was sharply decreased, while the ROS content was dramatically elevated in L02 cells treated with RPM, which can be partially restored after processing. CONCLUSIONS: The hepatotoxicity induced by RPM was significantly lower than the PMP, and its potential mechanism is associated with ferroptosis.

An enhanced cardio-protective effect of nanoparticles loaded with active components from Polygonum orientale L. against isoproterenol-induced myocardial ischemia in rats.

In this study, nanoparticles loaded with active components from Polygonum orientale L. (PO), a traditional Chinese herb known for its anti-myocardial ischemic properties, were investigated for cardio-protective properties. Specifically, OVQ-Nanoparticles (OVQ-NPs) with Orientin (Ori), Vitexin (Vit), and Quercetin (Que) was obtained by double emulsion-solvent evaporation method. The OVQ-NPs exhibited a spherical shape, with a uniform size distribution of 136.77 ± 3.88 nm and a stable ζ-potential of -13.40 ± 2.24 mV. Notably, these nanoparticles exhibited a favorable sustained-release characteristic, resulting in an extended circulation time within the living organism. Consequently, the administration of these nanoparticles resulted in significant improvements in electrocardiograms and heart mass index of myocardial ischemic rats induced by isoproterenol, as well as decreased serum levels of CK, LDH, and AST. Furthermore, the results of histopathological examination, such as H&E staining and TUNEL staining, confirmed a reduced level of cardiac tissue pathology and apoptosis. Moreover, the quantification of biochemical indicators (SOD, MDA, GSH, NO, TNF-α, and IL-6) demonstrated that OVQ-NPs effectively mitigated myocardial ischemia by regulating oxidative stress and inflammatory pathways. In conclusion, OVQ-NPs demonstrate promising therapeutic potential as an intervention for myocardial ischemia, providing a new perspective on traditional Chinese medicine treatment in this area.

Phytochemical analysis and hepatotoxicity assessment of braised Polygoni Multiflori Radix (Wen-He-Shou-Wu).

Polygoni Multiflori Radix (PMR) is a medicinal herb commonly used in China and Eastern Asia. Recently, the discovery of hepatotoxicity in PMR has received considerable attention from scientists. Processing is a traditional Chinese medicine technique used for the effective reduction of toxicity. One uncommon technique is the braising method-also known as 'Wen-Fa' in Chinese-which is used to prepare tonics or poisonous medications. Braised PMR (BPMR)-also known as 'Wen-He-Shou-Wu'-is one of the processed products of the braising method. However, the non-volatile components of BPMR have not been identified and examined in detail, and therefore, the hepatotoxic advantage of BPMR remains unknown. In this study, we compared the microscopic characteristics of different samples in powder form using scanning electron microscopy (SEM), investigated the non-volatile components, assessed the effects of different processed PMR products on the liver, and compared the differences between BPMR and PMR Praeparata recorded in the Chinese Pharmacopoeia (2020 edition). We found that the hepatotoxicity of BPMR was dramatically decreased, which may be related to an increase in polysaccharide content and a decrease in toxic substances. The present study provides an important foundation for future investigations of the processing mechanisms of BPMR.

Phytochemical profiling, in vitro biological activities, and in silico (molecular docking and absorption, distribution, metabolism, excretion, toxicity) studies of Polygonum cognatum Meissn.

Polygonum cognatum Meissn, a perennial herbaceous belonging to the Polygonaceae family, is an aromatic plant. High-performance liquid chromatography/diode array detector method was developed and validated for the phytochemical analysis of the plant. Also, various methods were used to investigate the antioxidant, antimicrobial, and cytotoxic activities of the methanolic extracts. Antioxidant activities were researched by 2,2'-diphenyl-1-picrylhydrazyl and cupric reducing antioxidant capacity methods. Among the tested standard microbial strains, Candida albicans was found to be more sensitive with a 24.60 ± 0.55 mm inhibition zone according to the diffusion tests. In the microdilution tests, the minimum inhibitory concentration and minimum bactericidal/fungicidal concentration values were 4.75 and ≥ 4.75 mg/mL, respectively, for all tested pathogens. Human colon carcinoma cells were used to investigate cytotoxicity by using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide analysis (IC50  = 2891 µg/mL for Plant A, IC50  = 3291 µg/mL for Plant B). Molecular docking and absorption, distribution, metabolism, excretion, and toxicity analysis were used to explain inhibition mechanisms of major phenolic compounds of plants against Tankyrase 1, Tankyrase 2 enzymes, and deoxyribonucleic acid gyrase subunit B and found compatible with experimental results.

Evaluation of antidiabetic and antioxidant effects of Polygonum cognatum Meisn. and phytochemical analysis of effective extracts.

Polygonum cognatum Meisn. (Polygonaceae) is used both as food and as a folk medicine to treat diabetes. This study aimed to evaluate the effect of the extracts, along with isolated compounds, from P. cognatum aerial parts on diabetes. In vitro studies were conducted using an α-glucosidase inhibitory assay, while in vivo antidiabetic studies were carried out on streptozotocin-induced diabetic rats. Effective extracts were subjected to isolation studies, and structures of the compounds were elucidated by spectroscopic methods. The ethyl acetate and n-butanol extracts had the highest effect in both in vitro and in vivo experiments. They also decreased aspartate transaminase, alanine transaminase and malondialdehyde levels, while increasing glutathione and superoxide dismutase activity in rats. From the active extracts, 11 phenolic compounds were isolated and characterized. Among the isolated compounds, quercetin was found to be the most active according to α-glucosidase inhibitory activity studies. This study provided scientific evidence for the traditional use of P. cognatum as a folk medicine for treating diabetes. The findings suggest that the ethyl acetate and n-butanol extracts, as well as quercetin, have the potential for development as antidiabetic agents.

Chemical profiling and investigation of molecular mechanisms underlying anti-hepatocellular carcinoma activity of extracts from Polygonum perfoliatum L.

Polygonum perfoliatum L. is an herbal medicine that has been extensively used in traditional Chinese medicine to treat various health conditions ranging from ancient internal to surgical and gynecological diseases. Numerous studies suggest that P. perfoliatum extract elicits significant anti-tumor, anti-inflammatory, anti-bacterial, and anti-viral effects. Nevertheless, the underlying mechanisms of its anti-liver cancer effects remain poorly understood. Our study suggests that P. perfoliatum stem extract (PPLA) has a favorable safety profile and exhibits a significant anti-liver cancer effect both in vitro and in vivo. We identified that PPLA activates the cGMP-PKG signaling pathway, and key regulatory genes including ADRA1B, PLCB2, PRKG2, CALML4, and GLO1 involved in this activation. Moreover, PPLA modulates the expression of genes responsible for the cell cycle. Additionally, we identified four constituents of PPLA, namely taxifolin, myricetin, eriodictyol, and pinocembrin, that plausibly act via the cGMP-PKG signaling pathway. Both in vitro and in vivo experiments confirmed that PPLA, along with its constituting compounds taxifolin, myricetin, and eriodictyol, exhibit potent anti-cancer activities and hold the promise of being developed into therapeutic agents.

The traditional herb Polygonum hydropiper from China: a comprehensive review on phytochemistry, pharmacological activities and applications.

CONTEXT: Polygonum hydropiper L. (Polygonaceae) (PH) is a traditional Chinese traditional medicine with a pungent flavor and mild drug properties. PH is mainly distributed in the channel tropism in the stomach and large intestine. PH has multiple uses and can be used to treat a variety of diseases for a long time. OBJECTIVE: This review summarizes the phytochemical and pharmacological activities, and applications of PH from 1980 to 2022. We also provide suggestions for promoting further research and developing additional applications of PH. METHODS: The data and information on PH from 1980 to 2022 reviewed in this article were obtained from scientific databases, including Science Direct, PubMed, Science Citation Index, SciFinder Scholar (SciFinder), Springer, American Chemical Society (ACS) Publications, and China National Knowledge Infrastructure (CNKI), etc. Some information was obtained from classic literature on traditional Chinese medicines. The search terms were Polygonum hydropiper, phytochemistry compositions of Polygonum hydropiper, pharmacological activities of Polygonum hydropiper, and applications of Polygonum hydropiper. RESULTS: The comprehensive analysis of the literature resulted in 324 compounds being isolated, identified, and reported from PH. Regarding traditional uses, the majority of phytochemical and pharmacological studies have indicated the diverse bioactivities of PH extracts, flavonoids, and volatile oil elements, including antibacterial, antifungal, insecticidal, antioxidant, and anti-inflammatory. CONCLUSIONS: PH has a long history of diversified medicinal uses, some of which have been verified in modern pharmacological studies. Further detailed studies are required to establish scientific and reasonable quality evaluation standards and action mechanisms of active constituents from PH.

Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice.

OBJECTIVE: Recent investigations have demonstrated that Polygonum perfoliatum L. can protect against chemical liver injury, but the mechanism behind its efficacy is still unclear. Therefore, we studied the pharmacological mechanism at work in P. perfoliatum protection against chemical liver injury. METHODS: To evaluate the activity of P. perfoliatum against chemical liver injury, levels of alanine transaminase, lactic dehydrogenase, aspartate transaminase, superoxide dismutase, glutathione peroxidase and malondialdehyde were measured, alongside histological assessments of the liver, heart and kidney tissue. A nontargeted lipidomics strategy based on ultra-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry method was used to obtain the lipid profiles of mice with chemical liver injury and following treatment with P. perfoliatum; these profiles were used to understand the possible mechanisms behind P. perfoliatum's protective activity. RESULTS: Lipidomic studies indicated that P. perfoliatum protected against chemical liver injury, and the results were consistent between histological and physiological analyses. By comparing the profiles of liver lipids in model and control mice, we found that the levels of 89 lipids were significantly changed. In animals receiving P. perfoliatum treatment, the levels of 8 lipids were significantly improved, relative to the model animals. The results showed that P. perfoliatum extract could effectively reverse the chemical liver injury and significantly improve the abnormal liver lipid metabolism of mice with chemical liver injury, especially glycerophospholipid metabolism. CONCLUSION: Regulation of enzyme activity related to the glycerophospholipid metabolism pathway may be involved in the mechanism of P. perfoliatum's protection against liver injury. Please cite this article as: Peng L, Chen HG, Zhou X. Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice. J Integr Med. 2023; 21(3): 289-301.

HPLC-DAD-MS3 fingerprints of phenolics of selected Polygonum taxa and their chemometric analysis.

Many Polygonaceae taxa such as Bistorta officinalis, Persicaria amphibia, Persicaria hydropiper, Persicaria lapathifolia, Persicaria maculosa, Persicaria mitis, Polygonum aviculare occur naturally in the entire territory of Poland and are also common in other European countries. Many of these species are also utilised as medicinal plants. In this manuscript we establish the phytochemical profiles of selected taxa from the Polygonaceae focusing on phenolics. Additionally, we try to find chemophenetic markers for the species investigated. Compounds were detected and characterised based on HPLC-DAD-MS data, quantified, and furtherly analysed using multivariate analyses. Chemophenetic markers were identified also considering previous literature.

Photosynthesis-related physiology and metabolomics responses of Polygonum lapathifolium in contrasting manganese environments.

Manganese (Mn) plays an essential role in plant growth; however, excessive Mn is toxic to plants. Polygonum lapathifolium Linn. was tested as a novel Mn-hyperaccumulating species in our previous study, but the underlying mechanisms of this hyperaccumulation are poorly understood. A hydroponic experiment with (8mmolL-1 ) and without additional Mn (CK) was established to explore the possible mechanisms through the effects on photosynthesis-related physiological characteristics and metabolomics. The results showed that additional Mn increased plant biomass, photosynthesis, and stomatal conductance related to increases in the effective photochemical quantum yield of photosystem II and relative electron transport rate (P <0.05). The results from liquid chromatography-mass spectrometry revealed 56 metabolites differentially accumulated between the plants composing these two groups. Metabolites were enriched in 20 metabolic pathways at three levels (environmental information processing, genetic information processing, and metabolism), of which five metabolic pathways were associated with significant or extremely significant changes (P <0.05). These five enriched pathways were ABC transporters (environmental information processing), aminoacyl-tRNA biosynthesis (genetic information processing), biosynthesis of amino acids , d -arginine and d -ornithine metabolism , and arginine biosynthesis (metabolism). Flavonoids may play a key role in Mn tolerance, as they accumulated more than 490-fold, and the relationship between flavonoids and Mn tolerance needs to be studied in the future.

Pharmacokinetic characteristics of emodin in polygoni Multiflori Radix Praeparata.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygoni Multiflori Radix Praeparata (Zhiheshouwu) has been a Wudang Taoist medicine for tonifying the liver and kidney, resolving turbidity and reducing lipid. Emodin is one of the active anthraquinones in Zhiheshouwu. Our previous studies showed that emodin (EM) and the other anthraquinones in Zhiheshouwu extract (HSWE) exerted similar inhibitory effects on liver cancer cells in vitro. However, it is still unknown if the other anthraquinones enhance pharmacokinetics (PK) of EM in HSWE in vivo. AIM OF THE STUDY: In this study, we compared the PK characteristics of EM alone with that in Zhiheshouwu aiming to explore which anthraquinones in HSWE contribute to the changed PK of EM in rats. MATERIALS AND METHODS: Quality control of HSWE was determined using high performance liquid chromatography (HPLC). The ratios of emodin to other anthraquinones, physcion (PH), chrysophanol (CH), rhein (RH), aloe-emodin (AE), emodin-8-O-ß-D-glycoside (EMG), physcion-1-O-ß-D-glycoside (PHG) and chrysophanol-8-O-ß-D-glycoside (CHG) in HSWE were determined and analyzed using UPLC combined with tandem mass spectrometry (UPLC/MS). The PK parameters and intestinal tissue concentration of EM alone, EM in HSWE, or with other anthraquinones in SD rats were analyzed using UPLC/MS. RESULTS: The quality of the Zhiheshouwu samples met the quality standard of the Chinese Pharmacopoeia (Version 2020). The PK results showed that compared with EM alone, Cmax (239.90 ± 146.71 vs. 898.46 ± 291.62, P < 0.001), Tmax (0.26 ± 0.15 vs. 12.55 ± 1.33, P < 0.001), AUC0-t (1575.09 ± 570.46 vs. 12154.96 ± 5394.25, P < 0.001), and AUC0-∞ (4742.51 ± 1837.62 vs. 37131.34 ± 21647.39, P < 0.001) of EM in HSWE were decreased due to PH and EMG, while the values of Vd (380.75 ± 217.74 vs. 11.75 ± 7.35, P < 0.001), T1/2 (10.81 ± 1.99 vs. 6.65 ± 2.76, P < 0.05) and CL (19.30 ± 7.82 vs. 2.78 ± 1.88, P < 0.001) of EM in HSWE were increased due to PH and AE. In addition, the intestinal tissue concentration of emodin in HSWE was decreased compared with that of EM alone in 20 and 780 min (25.37 ± 5.98 vs. 43.29 ± 4.16 and 26.72 ± 4.03 vs. 43.40 ± 14.19, respectively. P < 0.05) dominantly due to RH and PH. CONCLUSION: In conclusion, compared with treatment of EM alone, the AUC0-t value of EM in HSWE was decreased with different ways in rats. PH shortened Tmax, and increased Vd and CL. While AE prolonged T1/2 of EM. This indicated that the other anthraquinones in HSWE changed the PK of EM in rats and participated in the complex effects of EM on liver cancer. Besides the other anthraquinones, other components (e.g., 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside) in Zhiheshouwu may contribute in the pharmacokinetic and pharmacodynamic interactions with EM for anti-liver cancer.

Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice / 中西医结合学报

OBJECTIVE@#Recent investigations have demonstrated that Polygonum perfoliatum L. can protect against chemical liver injury, but the mechanism behind its efficacy is still unclear. Therefore, we studied the pharmacological mechanism at work in P. perfoliatum protection against chemical liver injury.@*METHODS@#To evaluate the activity of P. perfoliatum against chemical liver injury, levels of alanine transaminase, lactic dehydrogenase, aspartate transaminase, superoxide dismutase, glutathione peroxidase and malondialdehyde were measured, alongside histological assessments of the liver, heart and kidney tissue. A nontargeted lipidomics strategy based on ultra-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry method was used to obtain the lipid profiles of mice with chemical liver injury and following treatment with P. perfoliatum; these profiles were used to understand the possible mechanisms behind P. perfoliatum's protective activity.@*RESULTS@#Lipidomic studies indicated that P. perfoliatum protected against chemical liver injury, and the results were consistent between histological and physiological analyses. By comparing the profiles of liver lipids in model and control mice, we found that the levels of 89 lipids were significantly changed. In animals receiving P. perfoliatum treatment, the levels of 8 lipids were significantly improved, relative to the model animals. The results showed that P. perfoliatum extract could effectively reverse the chemical liver injury and significantly improve the abnormal liver lipid metabolism of mice with chemical liver injury, especially glycerophospholipid metabolism.@*CONCLUSION@#Regulation of enzyme activity related to the glycerophospholipid metabolism pathway may be involved in the mechanism of P. perfoliatum's protection against liver injury. Please cite this article as: Peng L, Chen HG, Zhou X. Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice. J Integr Med. 2023; 21(3): 289-301.

Chemical Composition of Essential Oils of Seven Polygonum Species from Turkey: A Chemotaxonomic Approach.

Medicinal plants and herbal preparations are gaining attention in the scientific community today, as they are often used intermittently in the treatment of various diseases. The genus of Polygonum (Polygonaceae), known locally as "madimak", is an aromatic plant widely used in world flavors. The chemical composition of the essential oils of dried aerial parts of seven of Polygonum was analyzed by GC-MS. These species are Polygonum lapathifolium L., Polygonum persicaria L., Polygonum arenastrum Bor., Polygonum bellardii All., Polygonum arenarium Waldst. Et Kit., Polygonum aviculare L., and Polygonum cognatum Meissn. Qualitative and quantitative differences were found in the essential oil analysis of the seven Polygonum species. The major compounds were determined as (E)-ß-farnesene (19. 46%), dodecanal (15.92%), ß-caryophyllene (12.95%), in P. aviculare; (E)-ß-farnesene (25.00%), dodecanal (20.45%), ß-caryophyllene (9.38%), and caryophyllene oxide (8. 26%) in P. persicaria; dodecanal (25.65%), caryophyllene oxide (13.35%), ß-caryophyllene (7.95%), and (E)-ß-farnesene (6.20%) in P. lapathifolium, and dodecanal (19.65%), (E)-ß-farnesene (13.86%), ß-caryophyllene (8.06%), and α-terpineol (7.2%) in P. arenarium, dodecanal (16.23%), ß-caryophyllene (16.09%), (E)-ß-farnesene (12.26%), caryophyllene oxide (7.94%) in P. bellardii, (E)-ß-farnesene (20.75%), dodecanal (17.96%), ß-caryophyllene (13.01%), α-terpineol (4.97%) in P. arenastrum, (E)-ß-farnesene (9.49%), dodecanal (14.01%), ß-caryophyllene (11.92%), geranyl acetate (9.49%), and undecanal (7.35%) in P. cognatum. This study is the most comprehensive study conducted to determine the essential oil components of Polygonum species. In addition, a literature review on the composition of the essential oils of these Polygonum taxa was performed. The essential oil components of the species in our study were revealed for the first time with this study.

Analyze the Effect of Steaming on the Chemical Constituents, Defecation and Liver Injury of Polygonum Multiflorum Radix (Heshouwu) by Multiple Analysis Techniques Combined with Multivariate Statistics.

Steaming is a characteristic pharmaceutical skill in Traditional Chinese Medicine (TCM). Polygonum multiflorum radix (PM) and its steamed products have been used in Asia for centuries. Raw Polygonum multiflorum radix (RPM) is commonly used to promote defecation but can exert toxicity, especially in liver injury. However, RPM can be made converted into Polygoni multiflori radix praeparata (PMP) by steaming; this is considered a good method to reduce defecation and liver injury caused by PM in Asia. The chemical constituents of TCM are the key to its action. We systematically analyzed the effect of steaming on PM constituents, defecation, and liver injury. We identified 13 main constituents from PM and PMP; the results showed that after being steamed, two constituents (TSG, catechin) had decreased, six constituents (such as procyanidin B1 or B2) had disappeared, four constituents (such as emodin, physcion) had increased, emodin-8-O-ß-D-glucoside remained unchanged in PMP. Pharmacological experiments showed that PM could promote defecation; however, there were no obvious effects in response to PMP. Only a high dose of PM for 14 days caused some degree of liver injury, although this injury disappeared after 14 days of drug withdrawal. Network pharmacology and molecular docking studies showed that TSG, emodin and physcion were the most effective in promoting defecation and causing liver injury. Collectively, our findings show that steaming can reduce the effect of PM on promoting defecation and reducing liver injury. TSG may be one of the important constituents in PM that can promote defecation and cause liver injury.

Polygonum capitatum, the Hmong Medicinal Flora: A Comprehensive Review of Its Phytochemical, Pharmacological and Pharmacokinetic Characteristics.

Polygonum capitatum, known as "Tou Hua Liao" (Chinese name), is a crucial source of Hmong medicinal plants that has benefited human health for a long time. This folk-medicinal plant is widely distributed in the south-west of China for the treatment of various urologic disorders including urinary tract infections, pyelonephritis, and urinary calculus. The purpose of this paper was to provide a systematic and comprehensive overview of the traditional usages, botany, phytochemistry, pharmacology, pharmacokinetics and clinical applications of this flora. Up until the end of 2022, at least 91 compounds had been reported from P. capitatum, mainly covering the classes of flavonoids, lignanoids, phenols and other components. The compounds and extracts isolated from P. capitatum exhibit a wide range of pharmacological activities, such as anti-inflammatory, antioxidant, antimicrobial, anticancer, analgesic, hypothermic, diuretic and other pharmacological effects. Qualitative and quantitative chemical analyses were also covered. Furthermore, the possible development trends and perspectives for future research on this medicinal plant were also discussed.

Exploratory Quality Control Study for Polygonum multiflorum Thunb. Using Dinuclear Anthraquinones with Potential Hepatotoxicity.

In recent years, the hepatotoxicity of Polygoni Multiflora Radix (PMR) has attracted increased research interest. Some studies suggest that anthraquinone may be the main hepatotoxic component. Most of the relevant studies have focused on the mononuclear anthraquinone component rather than binuclear anthraquinones. The hepatotoxicity of dinuclear anthraquinone (dianthrone) was investigated in a cell-based model. Next, a method for the determination of six free and total dianthonones in PMR and PMR Praeparata (PMRP) was established using ultra-high-performance liquid chromatography triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS), which was then used to analyze the collected samples. The data show that four binuclear anthraquinone compounds were hepatotoxic and may be potential toxicity indicators for the safety evaluation of PMR and PMRP. Herein, we provide a theoretical basis for the improvement of PMRP quality standards.

Electrochemical determination of emodin in acidic media by high-performance liquid chromatography and its application to Polygoni Multiflori Radix samples.

Electrochemical reduction of emodin under acidic media occurs at a less negative potential when compared with that under neutral media. When emodin is electrochemically detected at a less negative potential, a decrease in background noise and improvement in specificity benefit the development of high-performance liquid chromatography with electrochemical detection (HPLC-ECD) for its determination. HPLC-ECD was performed using an octadecyl silica column, acetonitrile-water (60:40, v/v) containing 5 mmol L-1 hydrochloric acid and 10 mmol L-1 lithium perchlorate, as a mobile phase, and an applied potential at - 0.4 V vs. Ag/AgCl. Under these optimal HPLC-ECD conditions, the detection limit (signal-to-noise ratio, S/N = 3) of emodin was 0.61 µg L-1. When this HPLC-ECD system was applied to the determination of emodin in Polygoni Multiflori Radix (PMR) samples, other peaks did not appear close to the emodin peak on a chromatogram. The emodin contents in PMR samples were determined with relative standard deviations (RSDs, n = 6) of less than 3.9%, and their recoveries ranged from 92 to 106%. We have shown that our HPLC-ECD system performed an accurate, precise, and specific determination of emodin in PMR samples.

Quercetin-Rich Ethanolic Extract of Polygonum odoratum var Pakphai Leaves Decreased Gene Expression and Secretion of Pro-Inflammatory Mediators in Lipopolysaccharide-Induced Murine RAW264.7 Macrophages.

Polygonum odoratum var. Pakphai has been used in traditional Thai medicine for the treatment of flatulence and constipation and to relieve the inflammation caused by insect bites. Quercetin (Q), which is abundant in plant-based foods, has been found to exert anti-inflammatory properties. This study evaluated the anti-inflammatory activity of P. odoratum ethanolic extract in RAW264.7 macrophage cells. Leaves were extracted with 50% ethanol, phenolics and flavonoids were then analyzed using UHPLC-QTOF-MS and HPLC-DAD. RAW264.7 cells were induced with lipopolysaccharides (LPSs). They were then treated with the extract and prostaglandin E2 (PGE2), and interleukin-6 (IL-6) and tumor necrotic factor-alpha (TNF-α) concentrations were determined. Levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), IL-6 and TNF-α mRNAs were analyzed using qRT-PCR. Chemical analysis demonstrated that the extract was abundant with Q while also containing catechin, gallic acid, epicatechin gallate and coumarin. The extract increased the viability of RAW264.7 cells and dose-dependently decreased nitric oxide production, PGE2, IL-6 and TNF-α levels in the medium from the LPS-induced RAW264.7 cell culture. Consistently, COX-2, iNOS, IL-6 and TNF-α mRNA levels were decreased in a concentration-dependent manner (p < 0.05). Thus, the quercetin-rich ethanolic extract derived from P. odoratum var Pakphai leaves can exert anti-inflammatory activity in LPS-induced RAW264.7 cells through a reduction of the pro-inflammatory mediator response.

Systematically Exploring the Chemical Ingredients and Absorbed Constituents of Polygonum capitatum in Hyperuricemia Rat Plasma Using UHPLC-Q-Orbitrap HRMS.

Polygonum capitatum as an ethnic medicine has been used to treat urinary tract infections, pyelonephritis and urinary calculi. In our previous study, P. capitatum was found to have anti-hyperuricemia effects. Nevertheless, the active constituents of P. capitatum for treating hyperuricemia were still unclear. In this study, an ultra-high-performance liquid chromatography coupled to quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to comprehensively detect the chemical ingredients of P. capitatum and its absorbed constituents in the plasma of hyperuricemia rats for the first time. Xcalibur 3.0 and Compound Discoverer 2.0 software coupled to mzCloud and ChemSpider databases were utilized for qualitative analysis. A total of 114 chemical components including phenolics, flavonoids, tannins, phenylpropanoids, amino acids, amides and others were identified or tentatively characterized based on the exact mass, retention time and structural information. Compared to the previous P. capitatum study, an additional 66 different components were detected. Moreover, 68 related xenobiotics including 16 prototype components and 52 metabolites were found in the plasma of hyperuricemia rats. The metabolic pathways included ring fission, hydrolysis, decarboxylation, dehydroxylation, methylation, glucuronidation and sulfation. This work may provide important information for further investigation on the active constituents of P. capitatum and their action mechanisms for anti-hyperuricemia effects.

Polygonum multiflorum Thunb. Induces hepatotoxicity in SD rats and hepatocyte spheroids by Disrupting the metabolism of bilirubin and bile acid.

ETHNOPHARMACOLOGICAL RELEVANCE: The liver damage associated with Polygonum multiflorum Thunb. (P. multiflorum) and its preparations have aroused widespread concern. Opinions on the toxicity mechanisms and targets of P. multiflorum vary, and the toxic components are even more controversial. However, based on the current research results, we believed that any single component in P. multiflorum could not directly lead to liver injury, but may be the synergistic effect of multiple components. In addition, the toxicity mechanism also involved multiple targets. AIM OF THE STUDY: This study aimed to elucidate the mechanism and target of the hepatotoxicity of P. multiflorum. MATERIALS AND METHODS: In this study, the manifestations of liver injury triggered by P. multiflorum and the associated metabolic enzymes/transporters in the metabolic pathways of bilirubin and bile acid were investigated to elucidate the mechanism and target of the hepatotoxicity of P. multiflorum and related components. First, the hepatotoxicity and potential effect of P. multiflorum on both metabolic pathways were studied in rats administered P. multiflorum extracts (in 70% ethanol) for 42 days. Then, in vitro cultured hepatocyte spheroids were used to determine the hepatotoxicity of monomer components. RESULTS: This revealed that P. multiflorum could simultaneously block bilirubin(BIL) and bile acid(BA) metabolism pathways, subsequently leading to liver damage. The targets and modes of action include reducing the activity of UGT1A1, the only metabolic enzyme of BIL, downregulating BIL and BA uptake transporters NTCP, OATP1B1, OATP1B3, efflux transporters MRP2, and BSEP, and upregulating efflux transporter MRP3. Furthermore, our data indicated that 2,3,5,4'-tetrahydroxystilbene-2-O-ß-glucoside (TSG) and emodin-8-O-ß-D-glucoside (EG) are the main toxic components in P. multiflorum. TSG accounts for 3.71% of the total content of P. multiflorum. In addition to markedly downregulating UGT1A1, TSG can upregulate OATP1B1/3 and promote the uptakes of bilirubin and bile acid, producing synergistic toxicity. EG accounts for 0.29% of the total content and demonstrates direct hepatotoxicity and extensive substrate overlap with bilirubin and bile acids. It can affect these two metabolic pathways simultaneously, promoting the accumulation of both bilirubin and bile acid for further toxic effects. Emodin is other major component, accounting for 0.01% of the total content, and its hepatotoxicity mechanisms include direct toxicity and inhibitory effects on bilirubin metabolizing enzymes. However, emodin is mainly distributed in the kidneys, so its hepatotoxicity risk is relatively low. CONCLUSION: The simultaneous blockade of bilirubin and bile acid metabolic pathways as the critical toxic mechanism of P. multiflorum-induced liver injury, and potential toxic components were TSG and EG.