Project description:Heshouwu (HSW), the dry roots of Polygonum multiflorum, a classical traditional Chinese medicine is used as a tonic for a wide range of conditions, particularly those associated with aging. However, it tends to be taken overdose or long term in these years, which has resulted in liver damage reported in many countries. In this study, the indicative roles of nine bile acids (BAs) were evaluated to offer potential biomarkers for HSW induced liver injury. Nine BAs including cholic acid (CA) and chenodeoxycholic acid (CDCA), taurocholic acid (TCA), glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), deoxycholic acid (DCA), glycodeoxycholic acid (GDCA), ursodeoxycholic acid (UDCA), and hyodeoxycholic acid (HDCA) in rat bile and serum were detected by a developed LC-MS method after 42 days treatment. Partial least square-discriminate analysis (PLS-DA) was applied to evaluate the indicative roles of the nine BAs, and metabolism of the nine BAs was summarized. Significant change was observed for the concentrations of nine BAs in treatment groups compared with normal control; In the PLS-DA plots of nine BAs in bile, normal control and raw HSW groups were separately clustered and could be clearly distinguished, GDCA was selected as the distinguished components for raw HSW overdose treatment group. In the PLS-DA plots of nine BAs in serum, the normal control and raw HSW overdose treatment group were separately clustered and could be clearly distinguished, and HDCA was selected as the distinguished components for raw HSW overdose treatment group. The results indicated the perturbation of nine BAs was associated with HSW induced liver injury; GDCA in bile, as well as HDCA in serum could be selected as potential biomarkers for HSW induced liver injury; it also laid the foundation for the further search on the mechanisms of liver injury induced by HSW.
Project description: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.
Project description:Polygonum multiflorum Radix (PMR) has long history in hair growth promotion and hair coloring in clinical applications. However, several crucial problems in its clinic usage and mechanisms are still unsolved or lack scientific evidences. In this research, C57BL/6J mice were used to investigate hair growth promotion activity and possible mechanism of PMR and Polygonum multiflorum Radix Preparata (PMRP). Hair growth promotion activities were investigated by hair length, hair covered skin ratio, the number of follicles, and hair color. Regulation effects of several cytokines involved in the hair growth procedure were tested, such as fibroblast growth factor (FGF-7), Sonic Hedgehog (SHH), β-catenin, insulin-like growth factor-1 (IGF-1), and hepatocyte growth factor (HGF). Oral PMR groups had higher hair covered skin ratio (100 ± 0.00%) than oral PMRP groups (48%~88%). However, topical usage of PMRP had about 90% hair covered skin ratio. Both oral administration of PMR and topically given PMRP showed hair growth promotion activities. PMR was considered to be more suitable for oral administration, while PMRP showed greater effects in external use. The hair growth promotion effect of oral PMR was most probably mediated by the expression of FGF-7, while topical PMRP promoted hair growth by the stimulation of SHH expression.
Project description:BackgroundDiabetes is a complex metabolic disease characterized by hyperglycemia, plaguing the whole world. However, the action mode of multi-component and multi-target for traditional Chinese medicine (TCM) could be a promising treatment of diabetes mellitus. According to the previous research, the TCM of Polygonum multiflorum (PM) showed noteworthy hypoglycemic effect. Up to now, its hypoglycemic active ingredients and mechanism of action are not yet clear. In this study, network pharmacology was employed to elucidate the potential bioactive compounds and hypoglycemic mechanism of PM.MethodsFirst, the compounds with good pharmacokinetic properties were screened from the self-established library of PM, and the targets of these compounds were predicted and collected through database. Relevant targets of diabetes were summarized by searching database. The intersection targets of compound-targets and disease-targets were obtained soon. Secondly, the interaction net between the compounds and the filtered targets was established. These key targets were enriched and analyzed by protein-protein interactions (PPI) analysis, molecular docking verification. Thirdly, the key genes were used to find the biologic pathway and explain the therapeutic mechanism by genome ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis. Lastly, the part of potential bioactive compounds were under enzyme activity inhibition tests.ResultsIn this study, 29 hypoglycemic components and 63 hypoglycemic targets of PM were filtrated based on online network database. Then the component-target interaction network was constructed and five key components resveratrol, apigenin, kaempferol, quercetin and luteolin were further obtained. Sequential studies turned out, AKT1, EGFR, ESR1, PTGS2, MMP9, MAPK14, and KDR were the common key targets. Docking studies indicated that the bioactive compounds could stably bind the pockets of target proteins. There were 38 metabolic pathways, including regulation of lipolysis in adipocytes, prolactin signaling pathway, TNF signaling pathway, VEGF signaling pathway, FoxO signaling pathway, estrogen signaling pathway, linoleic acid metabolism, Rap1 signaling pathway, arachidonic acid metabolism, and osteoclast differentiation closely connected with the hypoglycemic mechanism of PM. And the enzyme activity inhibition tests showed the bioactive ingredients have great hypoglycemic activity.ConclusionIn summary, the study used systems pharmacology to elucidate the main hypoglycemic components and mechanism of PM. The work provided a scientific basis for the further hypoglycemic effect research of PM and its monomer components, but also provided a reference for the secondary development of PM.
Project description:This study investigated the effects and mechanism of Heshouwu (Polygonum multiflorum Thunb.) water extract (HSW) on diabetes-related bone loss in mice. HSW was orally administered (300 mg/kg body weight) to high-fat diet and streptozotocin-induced diabetic mice for 10 weeks. HSW significantly alleviated mouse body weight loss and hyperglycemia compared with the control group, and elevated serum levels of insulin, osteocalcin, and bone-alkaline phosphatase. HSW supplementation also significantly increased the bone volume/tissue volume ratio and trabecular thickness and number, and decreased the bone surface/bone volume ratio and trabecular structure model index in the femur and tibia. Moreover, HSW significantly increased femoral bone mineral density. In addition, HSW down-regulated osteoclastogenic genes, such as nuclear factor of activated T-cells, cytoplasmic 1 and tartrate-resistant acid phosphatase 5 (TRAP), in both the femur and tibia tissue, and reduced serum TRAP level compare to those of control mice. These results indicate that HSW might relieve diabetes-related bone disorders through regulating osteoclast-related genes, suggesting HSW may be used as a preventive agent for diabetes-induced bone loss.
Project description:Objective:Based on in vitro and in vivo experimental studies, the changes of the main components of Polygonum multiflorum and different processed products and their effects on hepatotoxicity were investigated. Methods:The components of different processed products of Polygonum multiflorum and different processed products and their effects on hepatotoxicity were investigated. Results:With the extension of processing time, the contents of various chemical components in Polygonum multiflorum and different processed products and their effects on hepatotoxicity were investigated. Polygonum multiflorum and different processed products and their effects on hepatotoxicity were investigated. Polygonum multiflorum and different processed products and their effects on hepatotoxicity were investigated. Polygonum multiflorum and different processed products and their effects on hepatotoxicity were investigated. Conclusion:The content of the main components in Radix Polygonum multiflorum can be affected by processing time; stilbene glycoside may be the main component leading to liver injury. The degree of liver injury caused by Radix Polygonum multiflorum is negatively correlated with processing time.Polygonum multiflorum and different processed products and their effects on hepatotoxicity were investigated. Polygonum multiflorum and different processed products and their effects on hepatotoxicity were investigated.
Project description:Transcriptome profiling has been widely used to analyze transcriptomic variation in plants subjected to abiotic or biotic stresses. Although gene expression changes induced by methyl jasmonate (MeJA) have been profiled in several plant species, no information is available on the MeJA-triggered transcriptome response of Polygonum multiflorum Thunb., a species with highly valuable medicinal properties. In this study, we used transcriptome profiling to investigate transcriptome changes in roots of P. multiflorum seedlings subjected to a 0.25 mmol/L-MeJA root-irrigation treatment. A total of 18 677 differentially expressed genes (DEGs) were induced by MeJA treatment, of which 4535 were up-regulated and 14 142 were down-regulated compared with controls. These DEGs were associated with 125 metabolic pathways. In addition to various common primary and secondary metabolic pathways, several secondary metabolic pathways related to components with significant pharmacological effects were enriched by MeJA, including arachidonic acid metabolism, linoleic acid metabolism, and stilbenoid biosynthesis. The MeJA-induced transcriptome changes uncovered in this study provide a solid foundation for future study of functional genes controlling effective components in secondary metabolic pathways of P. multiflorum.
Project description:Seven new dianthrone glycosides, named polygonumnolides A1-B3 (1-7), were isolated from the 70 % EtOH extract of the dried roots of Polygonum multiflorum Thunb. using column chromatography and preparative high-performance liquid chromatography. Their structures were determined by 1D and 2D NMR and mass spectroscopy. The isolated compounds were evaluated for their cytotoxic effects against KB tumor cell lines and compounds 1-4 showed moderate cytotoxicity.
Project description:Currently, numerous liver injury cases related to a famous Chinese herb- Polygonum Multiflorum (Heshouwu in Chinese) have attracted great attention in many countries. Our previous work showed that Heshouwu-induced hepatotoxicity belonged to idiosyncratic drug-induced liver injury (IDILI). Unfortunately, the components and mechanisms attributed to IDILI of Heshouwu are difficult to determine and thus remain unknown. Attempts to explore puzzles, we prepared the chloroform (CH)-, ethyl acetate (EA)-, and residue (RE) extracts of Heshouwu to investigate IDILI constituents and underlying mechanisms, using biochemistry, histopathology, and metabolomics examinations. The results showed that co-treatment with non-toxic dose of lipopolysaccharide (LPS) and EA extract could result in evident liver injury, indicated by the significant elevation of plasma alanine aminotransferase and aspartate aminotransferase activities, as well as obvious liver histologic damage; whereas other two separated fractions, CH and RE extracts, failed to induce observable liver injury. Furthermore, 21 potential metabolomic biomarkers that differentially expressed in LPS/EA group compared with other groups without liver injury were identified by untargeted metabolomics, mainly involved two pathways: tricarboxylic acid cycle and sphingolipid metabolism. This work illustrated EA extract had close association with the idiosyncratic hepatotoxicity of Heshouwu and provided a metabolomic insight into IDILI of different extracts from Heshouwu.
Project description:Polygonum multiflorum (PM) Thunb., a typical Chinese herbal medicine with different therapeutic effect in raw and processed forms, has been used worldwide for thousands of years. However, hepatotoxicity caused by PM has raised considerable concern in recent decades. The exploration of toxic components in PM has been a great challenge for a long time. In this study, we developed a stepwise strategy integrating metabolomics and pseudotargeted spectrum-effect relationship to illuminate the potential hepatotoxic components in PM. First, 112 components were tentatively identified using ultraperformance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS). Second, based on the theory of toxicity attenuation after processing, we combined the UPLC-Q-TOF-MS method and plant metabolomics to screen out the reduced differential components in PM between raw and processed PM. Third, the proposed pseudotargeted MS of 16 differential components was established and applied to 50 batches of PM for quantitative analysis. Fourth, the hepatocytotoxicity of 50 batches of PM was investigated on two hepatocytes, LO2 and HepG2. Last, three mathematical models, gray relational analysis, orthogonal partial least squares analysis, and back propagation artificial neural network, were established to further identify the key variables affecting hepatotoxicity in PM by combining quantitative spectral information with toxicity to hepatocytes of 50 batches of PM. The results suggested that 16 components may have different degrees of hepatotoxicity, which may lead to hepatotoxicity through synergistic effects. Three components (emodin dianthrones, emodin-8-O-β-D-glucopyranoside, PM 14-17) were screened to have significant hepatotoxicity and could be used as toxicity markers in PM as well as for further studies on the mechanism of toxicity. Above all, the study established an effective strategy to explore the hepatotoxic material basis in PM but also provides reference information for in-depth investigations on the hepatotoxicity of PM.