| Type 2 diabetes mellitus(T2DM)is one of the metabolic diseases characterized by insulin resistance,high glucose and high fatty acid.In recent years,the incidence rate of diabetes has been increasing year by year,and is closely related to fatty liver disease.Nonalcoholic fatty liver disease(NAFLD)is a disease characterized by liver injury,hepatic steatosis and lipid metabolism disorder in addition to alcohol.It is mainly caused by the long-term or repeated exposure of the liver to high glucose and fatty acids.Fatty liver disease and diabetes are all comprehensive metabolic diseases,and there are many similarities between their etiology and pathogenesis.At present,there is no effective drug for the clinical prevention and treatment of T2 DM or NAFLD,and there is no effective auxiliary means for the fundamental treatment of NAFLD.Therefore,it is a hot spot for scholars to explore effective drugs with multi-component,multi-target and radical treatment of T2 DM or NAFLD from traditional Chinese medicine or ethnic medicine.Veratrilla baillonii Franch is the dry root of the genus veratrilla in Gentianaceae.It has been used for hundreds of years in Yunnan and other minority areas of China.It has the effects of clearing away heat and detoxification,killing insects,activating collaterals and relieving pain,and can be used to treat jaundice,gastroenteritis,dysentery,swelling and pain and other diseases.Our previous study on the chemical constituents of Veratrilla baillonii Franch showed that iridoid glycosides were the main active components of Veratrilla baillonii Franch,which had insulin-like effect and could significantly regulate the expression level of insulin pathway related genes.Therefore,we speculate that Veratrilla baillonii Franch may have some hypoglycemic and hepatoprotective activities.The aim of this study is to systematically study the anti diabetes and hepatoprotective activities of water extract of Veratrilla baillonii Franch(WVBF)by constructing related disease models in vivo and in vitro, so as to clarify the therapeutic effect and potential mechanism,and explore its potential value in clinical application.In this study,the following studies were carried out:(1)the therapeutic effect and mechanism of WVBF and its compounds on T2 DM mice model.(2)Objective to study the therapeutic effect and mechanism of WVBF and its compounds on NAFLD cell model.(3)Objective to study the therapeutic effect and mechanism of WVBF and its compounds on liver injury cell model.In order to elucidate the hypoglycemic and hepatoprotective effects of WVBF and its compounds and the underlying mechanism, the specific experimental contents are as follows:(1)The aim of this study was to investigate the hypoglycemic and hepatoprotective effects of WVBF and its Monomeric compounds on T2 DM mice.The results showed that WVBF and Gentiopicroside(GP)could improve the general state,body weight,blood glucose level,glucose tolerance(OGTT),insulin level and biochemical indexes of mice,and reduce the pathological damage of liver and kidney.In addition,WVBF can activate IRS-1 / PI3 K / Akt signaling pathway to improve the disorder of glucose and lipid metabolism,and the therapeutic effect of WVBF is better than that of single compound.These results suggest that WVBF and its Monomeric compounds can treat T2 DM mice by inhibiting oxidative stress,inflammatory reaction and insulin resistance,and its mechanism may be related to regulating insulin resistance signaling pathway,which is expected to become a new hepatoprotective drug for the treatment of glucose and lipid metabolism disorders.(2)In this study,NAFLD cell model was induced by appropriate amount of FFA in vitro.The pharmacodynamic difference and mechanism of WVBF and its compounds were studied by measuring the levels of cell viability,apoptosis,biochemical indexes(ALT,AST,SOD,GSH-Px,AKP,LPO),inflammatory cytokines(IL-6 and TNF-α),related genes and proteins.The results showed that WVBF and its compounds significantly improved the abnormal levels of SOD,GSH-Px,ALT,AST,AKP,MDA,LPO,IL-6 and TNF-α,the abnormal expression of PPAR α,SREBP-1c,FASN,ACC,TNF-α and Nrf2,and the abnormal expression of PPAR α,SREBP-1c,FASN and Nrf2.These results suggest that WVBF and its Monomeric compounds can treat NAFLD cell model by inhibiting oxidative stress,inflammatory reaction and lipid accumulation,and its mechanism may be related to regulating lipid synthesis and metabolism.(3)In this study,the cell viability,biochemical indexes(ALT,AST,SOD,GSH-Px,MDA)levels,inflammatory cytokines(IL-6 and TNF-α)and related gene expression levels were measured to study the therapeutic effect and mechanism of WVBF and its compounds.The results showed that WVBF and its Monomeric compounds could significantly improve cell viability,ALT,AST,SOD,GSH-Px,MDA and Nrf2,HO-1,MAPK8,NF-κB and TNF-α gene expression.These results suggest that WVBF and its Monomeric compounds can treat liver injury cell model by inhibiting oxidative stress and inflammation,and its mechanism may be related to the regulation of Nrf2 / HO-1 antioxidant stress pathway and MAPK8 /NF-κB / TNF-α inflammatory signal pathway.In conclusion,this study found that WVBF has significant anti-inflammatory,anti-oxidation and regulation of glucose and lipid metabolism,which can be used to treat NAFLD and liver injury.This not only reflects the multi-component,multi-target and multi-channel pharmacodynamic advantages of Veratrilla baillonii Franch,but also finds its potential medicinal value in the treatment of lipid metabolism disorder,and provides a scientific and reliable basis for its later research and application,It can promote the clinical application and efficacy research of ethnic medicine. |
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