Biological Activities And Mechanisms Of Polyphenols From Lachnum Sp.

In this study,intracellular polyphenol(LSP156)from Lachnum sp.YM156 was extracted by fermentation,extraction and purification,and its component was analyzed by liquid chromatography tandem mass spectrometry(LC-MS/MS).The hepatoprotective activity and its mechanism of LSP156 was explored,as well as the hypoglycemic effect.The results showed there were abundant flavonoids,tannins and phenolic acids in LSP156,incorporating daidzein,thymidine,isorhamnetin,bavachinin et al.In order to study whether LSP156 had the hepatoprotective activity,the model of acute hepatic damage was induced by N-Nitrosodiethylamine(NDEA).Compared with the NDEA model group,the results showed that LSP156 significantly reduced the levels of glutamic-oxalacetic transaminase(AST),glutamic-pyruvic transaminase(ALT),alkaline phosphatase(AKP),total cholesterol(TC),triglycerides(TG),tumor necrosis factor(TNF-?)and interleukin-6(IL-6),and increased superoxide dismutase(SOD)and catalase(CAT).Moreover,LSP156 reduced the hepatocyte injury caused by NDEA.The preliminary study has revealed that LSP156 has protective effect on the liver.To discuss the hepatoprotective activity and the mechanism of LSP156,N-Nitrosodiethylamine(NDEA)was used to establish liver injury model.The results showed that LSP156 could effectively increase the levels of SOD,CAT and glutathione(GSH),and reduce the contents of malondialdehyde(MDA),AST,ALT,AKP and total bilirubin(TBi L).Meanwhile,LSP156 significantly reduced the serum levels of TNF-? and IL-6 in liver injury mice.Compared with the model group,Western blotting analysis showed that LSP156 could reduce the expression levels of p-STAT3,TLR4 and COX-2.In addition,the result of high-throughput sequencing showed that LSP156 reduced the abundance of Bacteroides and Lactobacillus.Moreover,combining with correlation analysis,bacteroidaeceae was positively correlated with the important inflammatory factor(TNF-? and IL-6),leading to diminish inflammation.In summary,LSP156 could alleviate the acute liver injury by antioxidation,inhibiting inflammation and regulating the STAT3/COX-2 signaling pathway and intestinal flora,indicating its hepatoprotective activity and mechanism.The hyperglycemic mice model was established by streptozotocin,and thehypoglycemic effect and the mechanism of LSP156 was studied.In vitro Hypoglycemic experiment showed that LSP156 had a certain inhibitory effect on?-glucosidase,which indicated it had an effective hypoglycemic activity.Administration with LSP156,the weight gain rate,fasting blood glucose(FBG),pancreatic index and HOMA-? reduced,and HOMA-IR increased.At the same time,LSP156 also reduced the levels of AST and ALT in hyperglycemic mice.Compared with the model group,LSP156 significantly reduced the levels of MDA,GSH,TC,TG and free fatty acid(FFA),while the levels of SOD and CAT increased.In addition,the mechanism of action of LSP156 was studied by Real-time PCR and Western blotting.According to the result of RT-PCR,LSP156 at different doses significantly increased the m RNA expression level of IRS-2 and AKT in livers,while GSK-3?decreased.Combined with Western Blotting analysis,LSP156 reduced the expression level of GSK-3? and p-GSK-3?,and inhibited the activation of IRS-2 and AKT,indicating that LSP156 could regulate the blood glucose level through antioxidation,hypolipidemic effects and IRS/Akt/GSK-3? signal pathway.