Dataset Information

Water extract from processed Polygonum multiflorum modulate gut microbiota and glucose metabolism on insulin resistant rats.

ABSTRACT: BACKGROUND:The incidence of insulin resistance (IR) has rapidly increased worldwide over the last 20 years, no perfect solution has yet been identified. Finding new therapeutic drugs will help improve this situation. As a traditional Chinese medicine, PPM (processed Polygonum multiflorum) has widely been used in the clinic. Recently, other clinical functions of PPM have been widely analyzed. RESULTS:Administration of the water extract from PPM decreased the level of FBG, TC, and TG, and increased the level of FGC, thereby reducing the IR index and improving IR. Furthermore, Western blot analysis revealed that PPM significantly increased GPR43 and AMPK expression when compared with the MOD group, and GPR43, AMPK were known as glucose metabolism-related proteins. In addition, treatment with PPM can restore the balance of gut microbiota by adjusting the relative abundance of bacteria both at the phylum and genus level, and these changes have been reported to be related to IR. METHODS:Sprague Dawley (SD) rats were fed a high-fat diet and were gavaged daily with either normal saline solution or PPM for 12 weeks. Major biochemical indexes, such as fasting blood glucose (FBG), fasting glucagon (FGC), total cholesterol (TC), and triglyceride (TG) were measured. Then the protein expression of adenosine 5'-monophosphate -activated protein kinase (AMPK) and G protein-coupled receptor 43 (GPR43) was evaluated by using Western blot analysis. Moreover, the composition of gut microbiota was assessed by analyzing 16S rRNA sequences. CONCLUSIONS:Our findings showed that PPM reversed the increasing of FBG and the decreasing of IRI, PPM accelerated the expression of glucose metabolism-related proteins and regulated the intestinal microecological balance. Therefore, we hold the opinion that PPM may be an effective option for treating IR.

SUBMITTER: Gu W

PROVIDER: S-EPMC7132990 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Polygonum multiflorum [PM, synonym Reynoutria multiflora (Thunb.) Moldenke.], a well-known and commonly used Traditional Chinese Medicine and herbal dietary supplement for nourishing the kidney and liver, etc., has aroused wide concern for its reported potential hepatotoxicity. Previous clinical cases and experimental studies have suggested that mild immune stress (MIS) may be one of the susceptibility-related factors of idiosyncratic drug-induced liver injury (IDILI) caused by PM. In this paper, we found that the same dose of PM caused abnormal liver biochemical indicators and liver tissue damage in MIS model rats, while it did not result in liver injury in normal rats, further confirming that MIS is a susceptibility factor for PM-IDILI. Plasma chemokine/cytokine profiling indicated that the MIS model group was significantly different from the other groups, showing a significant upregulation of plasma chemokines, while the MIS/PM group showed upregulated expression of chemokines or pro-inflammatory cytokines. Liver histopathological examination indicated a small amount of inflammatory cytokine infiltration in the MIS group, but no hepatocyte injury, consistent with the plasma profiles of increased chemokines and unchanged inflammatory cytokines. Notably, metabolomics characterization showed that MIS caused reprogramming of these metabolic pathways (such as phenylalanine and glutamate pathways), which was associated with acute phase reactions and inflammatory responses. These results suggested that MIS may promote an immune response to the initial cellular injury induced by PM in the liver, and MIS-induced upregulation of chemokines and metabolic reprogramming may an important mechanism that mediates the susceptibility to PM-IDILI. Furthermore, via receiver operating characteristic (ROC) curves analysis, we identified 12 plasma cytokines (e.g., IP-10, MCP-1 and MIP-1α) and nine metabolomics biomarkers (e.g., L-Phenylalanine, Creatinine, and L-glutamine) with differential capabilities (all ROC AUC > 0.9) of identifying susceptibility model animals from normal ones, which might be of referable value for the clinical recognition of PM-IDILI susceptible individuals.

Project description: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.

Dataset Information

Water extract from processed Polygonum multiflorum modulate gut microbiota and glucose metabolism on insulin resistant rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets