Apigenin Improves NAFLD By Activating Nrf2

Non alcoholic fatty liver(NAFLD)is a kind of clinical pathological syndrome caused by a variety of factors with no excessive drinking history.It is often followed by obesity,type II diabetes and hyperlipidemia.The main features of NAFLD include hepatic steatosis and lipid accumulation.According to the progression of the disease,NAFLD can be divided into five categories including simple fatty liver,fat hepatitis,liver fibrosis,liver cirrhosis and even hepatocellular carcinoma.NAFLD affects human health seriously with approximately 20%people suffering from nonalcoholic fatty liver.Two strike theory indicates that several factors including metabolic disorder,oxidative stress,and systemic inflammation interact with each other and finally act together on NAFLD.Due to the complexity of the pathogenesis of NAFLD,it is still relatively lack of effective drugs to cure it.Therefore,it is necessary to develop the potential drugs for the treatment of NAFLD from many ways and reveal the mechanisms of those drugs.Apigenin is a natural flavonoid compounds with wide distribution in vegetables,fruits and other foods.The pharmacological activity of Apigenin contains anti-tumor,anti-inflammatory,antioxidant,anti-allergic,lowering blood pressure,lowering blood lipid,anti-artery hardening and cerebral thrombosis,sedative and anti-anxiety.Obviously,apigenin has showed multiple functions which match the pathogenesis of NAFLD well.In this study,we will study the treatment mechanisms of apigenin on NAFLD from the following aspects.1.The improvement effect of NAFLD by apigeninOxidative stress and lipid metabolism disorder caused by lipid peroxidation,mitochondrial dysfunction,oxidative stress and excessive free fatty acids,are the two crucial factors of NAFLD.(1)The establishment of a mouse model of NAFLD:we used high-fat diet to feed mice for 16 weeks,then detect fatty degeneration of liver tissue,oxidative stress,lipid metabolic disorders and other indicators to establish a mouse model of NAFLD;(2)The improvement effect of apigenin to NAFLD:Apigenin treated high-fat feeding mice for 21 days,the expression of lipid metabolism genes,antioxidant enzymes,antioxidant gene express in liver tissue was tested and the results showed that apigenin significantly reduced the fat degeneration of liver tissue;Significantly it increased the activities of antioxidant enzyme SOD,GSH-px,CAT.GSH,and expectedly,GSSG ratio significantly decreased;Carbonylation protein levels in serum and liver tissue were significantly lower;At the same time,the mRNA levels of NQO1,GSTM1,GSTA4,GCLC and GCLM gene in liver tissue,were significantly enhanced while lipid droplets related gene CIDEA,PLIN2,FITM1,FITM2,G0S2,lipid generated gene FABP1 NROB2 and lipid intake gene LPL were significantly lower by apigenin,suggesting that apigenin can significantly improve obesity induced oxidative stress and lipid metabolism disorders in the progress of NAFLD.2.The mechanism of apigenin improves the NAFLD(1)The establishment of NAFLD model in vitro:lipid droplets was detected after FFA treating Hep 1-6 cells for 24 hours.(2)Apigenin inhibited the progress of NAFLD through activation of Nrf2:Nrf2 is a drug targets in the treatment of NAFLD.This study found that apigenin can significantly promote the activation of Nrf2,and promoted Nrf2 translocating from the cytoplasm to the nucleus.By building Nrf2 knock down cell line,we found that after knockdown Nrf2,the effect of apigenin that up regulated genes including NQO1,GSTM1,GSTA4,GCLC,GCLM reduced or disappeared,suggesting that apigenin improve of NAFLD oxidative stress is dependent on Nrf2.Taken together,this study found that apigenin can improve obesity induced NAFLD,and reveals that apigenin inhibiting the progress of NAFLD is through activation of Nrf2 and regulating the expression of antioxidant genes and lipid metabolism.