Inhibitory Effect Of Chrysanthemum Morifolium Extract On Hyperlipidemic Fatty Liver Formation And Its Mechanisms In Mice

Aim: To examine the inhibitory effect of Chrysanthemum morifolium extract(CME) on hyperlipidemic fatty liver in mice and investigate the potential mechanisms.Methods: Male mice were used and randomly divided into the control, model,CME75,150, and300mg/kg groups, and positive drug lipanthyl40mg/kg group. Amouse model with hyperlipidemic fatty liver was induced by orally feeding high-fatmilk by gavage when they were simultaneously treated with drug for6weeks.Thereafter, the liver and blood were taken, the total cholesterol (TC), triglycerides (TG),and free fatty acids (FFA) in liver and serum as well as superoxide dismutase (SOD)and malondialdehyde (MDA) in hepatic tissue were measured with the colorimetricmethods, and the hepatic histological changes were examined under a light microscope.The mRNA and protein expressions of hepatic peroxisome proliferator-activatedreceptor (PPAR) α, sterol regulatory element binding protein (SREBP)-1c, fatty acidsynthase (FAS), diacylglycerol acyltransferase (DGAT), lipoprotein lipase (LPL), andcholesterol7α-hydroxylase (CYP7A)1were examined by RT-PCR and Western blotmethods, respectively. The cultured BRL cells were used to observe the effects ofCME-rich serum on intracellular TC, TG, and FFA contents as well as PPARα,SREBP-1c, FAS, LPL, and CYP7A1protein expressions. In order to determine whetherthe regulatory lipid mechanism of CME was associated with the pathway of PPARα,BRL cells were pretreated with PPARα inhibitor MK8861μmol/L for2h, the changesof SREBP-1c, FAS, and LPL protein expressions were then determined.Results: After treatment with CME75-300mg/kg for6weeks, the hepatic TC, TG,and MDA contents as well as hepatic weight coefficient were decreased (P<0.05orP<0.01), and the serum TC and TG contents were also decreased in some extent, whilethe hepatic SOD was increased (P<0.01). No significant reduction in the hepatic FFA level was observed in the CME-treated mice. Importantly, CME might significantlydecrease the degree of hepatic steatosis. RT-PCR and Western blot assays showed that inthe CME-treated groups, the hepatic SREBP-1c and FAS protein expressions weredecreased, and the hepatic PPARα, LPL, and CYP7A1protein expressions wereincreased (P<0.05or P<0.01). However, the expected reduction in hepatic DGATmRNA expression was not observed. In vitro, CME-rich serum might also decreaseintracellular TC, TG, and FFA contents as well as SREBP-1c and FAS proteinexpressions (P<0.05or P<0.01), and increase the LPL and PPARα protein expressions(P<0.05or P<0.01). And after pretreatment with PPARα inhibitor MK886, theregulatory effects of CME on SREBP-1c, FAS, and LPL protein expressions weredecreased or completely cancelled.Conclusion: CME might inhibit high-fat milk-induced fatty liver formation in mice,and its mechanisms might be related to increment of hepatic antioxidation andregulation of hepatic lipid metabolism-related target genes SREBP-1c, FAS, LPL, andCYP7A1expressions via increasing PPARα expression.