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Therapeutidcal Effects of Total Flavonoids of Litsea Coreana Level on Nonalcoholic Steatohepatitis and Its Partly Mechanisms of Action

Author: WangJianQing
Tutor: LiJun
School: Anhui Medical University,
Course: Pharmacology
Keywords: Non - alcoholic steatohepatitis The leopard skin camphor total flavonoids Toll-like receptor 4 Kupffer cells Antioxidant
CLC: R285.5
Type: Master's thesis
Year: 2007
Downloads: 59
Quote: 3
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Abstract


Non-alcoholic fatty liver disease (nonalcoholic fatty liver dieases, NAFLD) is the histopathological changes similar to alcoholic liver steatosis, hepatocellular injury and inflammatory cell infiltration, but no clear history of excessive alcohol consumption, a chronic liver disease. NAFLD showed mixed progress over the course of the disease, and four pathological processes, including simple steatosis, steatohepatitis (the nonalcoholic NASH NASH), fatty liver fibrosis and fatty liver cirrhosis. NASH NAFLD to liver fibrosis and cirrhosis important intermediate links. Its pathogenesis is still unknown, the major clinical lipid regulating drugs combined with hepatic cytoprotective agents or antioxidants for the prevention and treatment of NASH, but the safety and efficacy needs to be further evaluated. Litsea coreana aka Hawks tea, Department of Lauraceae Litsea genus Litsea rotundifolia (Litsea Coreana level), gross leaf, it is our long-term consumption of a plant south of the national folk alternative tea has a refreshing thirst quencher, detoxification swelling, eyesight stomach and other effects. Eagles tea contains more active ingredients, our hospital natural Department of Medicinal Chemistry, identified the Litsea coreana the effective parts for the total flavonoids (Total flavonoids). Experimental research data about the Hawks tea less its pharmacological effects only see the experimental study of the antioxidant, our previous studies have shown that the total flavonoids of Litsea coreana the (total Flavonoids of Litsea Coreana Level, TFLC) has a significant role in the anti-inflammatory immune NASH There are good preventive effect. This paper studies a the leopard skin camphor total flavonoids treatment of NASH and some of its mechanisms, the main content is summarized as follows: 1.TFLC therapeutic effect of SD rat NASH SD rats were first given fat emulsion induced NASH model. After three weeks, while giving TFLC (100,200,400 mg / kg), compared with model group, TFLC can significantly reduce serum ALT, AST, LDL-C, TC, TG, FFA and liver homogenates TC, TG, FFA level and a significant increase in serum HDL-C; elevated serum leptin (Leptin), insulin (INS) levels, lower serum levels of TNF-α. Histopathological examination results show that given TFLC can significantly alleviate liver fatty degeneration of the degree of inflammatory reaction VG staining results showed that give TFLC can significantly reduce the portal area of ??collagen fibers, and the RT-PCR results discovered TFLC can inhibit liver α-SMA mRNA expression, which inhibits hepatic stellate cell activation, prevention NASH progression to liver fibrosis. These results suggest that: TFLC significant role in the treatment of SD rats induced by high fat emulsion NASH. 2.TFLC SD rats NASH oxidative metabolism compared with the model group, TFLC significantly reduce liver homogenate MDA and serum NO content and SOD activity increased liver homogenates, while inhibiting CYP2E1 protein in liver. Electron microscopy of liver cell ultrastructure results show that given TFLC mitochondrial swelling is reduced significantly, the structure is more clear than the model group. The above results suggest that: TFLC therapeutic effect of SD rats NASH may be related to anti-lipid peroxidation inhibition of hepatic CYP2E1 expression and mitochondrial protective effect. 3.TFLC on NF-κB expression in rat Kupffer cells and related mechanisms TFLC (100 mg / L) can inhibit LPS stimulation in vitro rat liver Kupffer cells TLR4 mRNA expression; TFLC (200 mg / kg) significantly inhibited by the fat emulsion induced the NASH rat Kupffer cell membrane TLR4 and nucleus NF-κB protein expression. The: TFLC treatment of NASH its inhibitory activity of Kupffer cells. The above experimental results suggest that a significant therapeutic effect, TFLC fat emulsion-induced rat NASH. Its mechanism of action may be related to regulation of lipid metabolism; regulate oxidative metabolism by liver mitochondrial CYP2E1 expression, protection of the structure and function of liver mitochondria; NF-κB activation in Kupffer cells and by inhibiting TLR4 overexpression of Kupffer cell membrane, thereby reducing further inhibit cytokines TNF-α generation.

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