Xh-211 Lipid-lowering, Insulin Sensitizing Activity Of The Determination Of Its Mechanism

Background and purpose: Metabolic syndrome is a morbid state that involves several metabolic disturbances. It is tightly linked with cardiovascular disease including fat,hypertension and hyperlipidemia. Many investigations indicate that metabolic disturbance of lipid and glucose is the main motivation of the metabolic syndrome. Current medication is to control blood tension, hyperglycaemia and hyperlipidemia. There are few effective medications to treat hyperlipidemia and insulin resistance at the same time. To develop new medication to MS, the affection of compound XH-211 to lipid and sugar metabolism was established. Method: Set up the model of hyperlipidemia mice with high fat diet. The mice were divided into 5 groups: Normal group: normal diet; Model group: high fat diet; Low dosage group: high fat diet+50mg/kg compound XH-211; High dosage group: high fat diet+100mg/kg compound XH-211; Control drug group: high fat diet+200mg/kg Inositol Hexanicotinate. After 4 weeks therapy, lipids and glucose in serum were determined using Automatic Analyzer 7170A; leptin were established with ELISA assay; insulin were measured with radiation immunosorbent assay. The liver was measured through HE dyeing. Culture the 3T3-L1 in in vitro. Cell viability and lipid production in the differentiation process were determined by MTT and Oil-Red-O assay. PPARγgene expression exposed to compound XH-211 was observed through RT-PCR assay. The apoptosis induced by compound XH-211 was suggested by flow cytometry assay. Results: The in vivo study indicated that hyperlipidemia including higher LDL-C, TG and lower HDL-C was induced by high fat diet. Compound XH-211 could depress TG to 59.57% (P<0.05==, LDL-C to 81.65% (P<0.05= and increase HDL-C to 168.84% (P<0.05= compared with model group. Leptin and insulin concentration in plasma were depressed obviously (P<0.05=. Leptin and insulin sensitivity were elevated. The in vitro study suggested that compound XH-211 supressed the proliferation and lipid production of 3T3-L1, which inhibition ratio were 28.29% and 28.76% respectively. The PPARγgene expression was activated significantely(P<0.05=. The apoptosis of both pre-adipocytes and mature adipocytes were induced by compound XH-211 meanwhile, whose apoptosis ratios were 134.1% and 206% respectively compared with blank group. Conclusion: Compound XH-211 may improve insulin sensitivity through activating PPARγgene or through ameliorating leptin resistance. Meanwhile, leptin could induce apoptosis of 3T3-L1, then fat accumulation was suppressed and lipids in serum were improved, which was superior to TZDs.