Research Of The Efficacy And The Mechanism Of The Alisma Orientalis Methanolic Extract On Nonalcoholic Fatty Liver Disease

Objective: The aim of this investigation was to evaluate the efficacy and the potential mechanisms of the Alisma orientalis methanolic extract (AOME) on the experimental nonalcoholic fatty liver disease (NAFLD) induced by high fat diet.Method: All animals were randomly divided into six groups of 12 rats in each group. The rats of group Ⅰ was fed normal diet for 12 weeks, and the rats of the other five groups (group Ⅱ, group Ⅲ, group Ⅳ, group Ⅴand group Ⅵ) were fed with high fat diet. Six weeks later, blood was collected from the tails of all groups of rats and the main lipids and lipoproteins were measured. Make sure all the high fat diet treated rats were hyperlipidemia, the rats were then treated with the pharmacologic agents.Group Ⅱ (HD), rats were fed with high fat diet continuously and gavaged the ultrapure water daily;Group Ⅲ (FF), rats were fed with high fat diet continuously and gavaged the fenofibrae (100mg /kg) daily;Group Ⅳ (1-AOMEt), rats were fed with high fat diet continuously and gavaged the AOME (150mg/kg) daily;Group Ⅴ (m-AOME), rats were fed with high fat diet continuously and gavaged the AOME (300mg/kg) daily;Group Ⅵ (h-AOMEt), rats were fed with high fat diet continuously and gavaged the AOME (600mg/kg) daily. At the end of the twelfth-week treatment, all rats were anesthetized and decapitated. Blood samples were collected and serum was separated immediately for analysis of the biochemical parameters. Livers were dissected out. One portion of the liver tissue was fixed in10% neutral buffered formalin for histological analysis, and the remaining was snapped in liquid nitrogen and stored in -76 °C for estimation of the other various parameters. To evaluate the the potential mechanisms of the AOME on the experimental NAFLD induced by high fat diet. In the molecular mechanism study, we use RT-PCR to detect the mRNA expression of PPAR-α, TNF-α and ACO in the liver.Result: Feeding animals with high fat diet resulted in NAFLD.Administrated with the AOME showed remarkable hepatoprotective effects on the NAFLD rats. Markers of the liver injury, aminotransferase abnormalities and hepatomegaly induced by high fat diet were reversed. The AOME treatment ameliorated the dyslipidemia and the fat accumulation in the liver. High level of fasting serum glucose was reduced and insulin resistance was improved in the AOME treated rats. The AOME treatment for six weeks was also helpful in prevention of the oxidative stress by lessening the MDA level and activating the SOD activities. On histological examination, hepatic steatosis, mixed inflammation and collagen deposition were ameliorated in treat with the AOME. In the molecular mechanism study, the RT-PCR results showed that AOME up-regulated the mRNA levels of PPAR-α and ACO in the liver, and down-regulated the hepatic mRNA expression of TNF-α.Conclusion: These results suggested that the AOME showed remarkable hepatoprotective effects on the NAFLD rats by activating the hepatic mRNA expression of PPAR-α and ACO, ameliorating the dyslipidemia and the fat accumulation in the liver. Administrated with the AOME also succeeded in inhibiting the mRNA expression of the TNF-α in the liver, improving insulin resistance and palliating the oxidative stress. Mixed inflammation and collagen deposition in the liver were lessened in treat with the AOME.All results indicated that the AOME may be a potential clinical application in treat with this chronic liver disease.