Study Of The Preparation Of Apigenin’s Derivants And Their Anti-nonalcoholic Steatohepatitis Effects

Nonalcoholic steatohepatitis(NASH) is one kind of the nonalcoholic fatty liver disease(NAFLD). Researchers has paid attention increasingly to it because of its high prevalence rate and younger-rage incidence trend. The "twice strike" theority recognized that insulin resistance, oxidative stress and lipid proxidation damage are the main mechanism of NASH.Apigenin has many pharmacological effects, including anti-cancer, anti-inflammatory, anti-oxidation, anti-viral and anti-bacterial, et al. But epigenin’s poor solubility may vastly limits its absorption and distribution in body and limits its pharmacological effects.In this research, synthesis of apigenin derivate and their in-vitro\vivo activity study has been carried out to search a new way for NASH’s therapy. All the research results are as follows:(1) Synthesis of Apigenin derivates, including apigenin sulfonate,8-((dimethylamino)methyl)-apigenin,8-((4-methylpiperazin-1-yl)methyl)-apigenin,6,8-bis(morpholinomethyl)-apigenin. Select the derivats with better solubility and yield for the in-vitro\vivo activity study;(2) In-vitro tests for apigenin and its derivats on NASH L02 cell model, with a result that apigenin and some of the derivats can improve model cells’ lipidosis, inflammatory response and insulin resistance, et al, in a certain extent.(3) In-vivo tests for apigenin and its derivates on NASH mice model, with a result that apigenin and some of its derivates can improve part of the biochem indexes we tested, including INS/FFA/MDA/TNF-α in serum, and SOD/Lipid in liver, et al. Apigenin and especially its derivate A showed a wide and stronger effect for improving NASH.We attempt to built up a research foundation for NASH therapy through the way of in vitro and vivo tests with apigenin and its derivates.