Studies On Effects And Mechanisms Of Anti-obesity For Andrographolide

Obesity is a state of body’s energy intake imbalance and expenditure, which leads to body fat accumulation excessive and (or) abnormal distribution, also causes human pathology and physiology changes. Now it has become a worldwide public health problem. Digging safe and effective function ingredients from the natural plant, exploring their intervention on obesity has become a hot spot in the field of functional food and natural medicine research in recent years.Andrographolide (AG) is the major effective component of the Andrographis, which has the function of removing heat detoxification, anti-inflammatory and analgesic. But its physiology function about losing weight or reducing lipid has not yet been reported. In this paper, adipocyte model and obesity animal model were constructed, the methods of molecular probes, fluorescence marker, cell differentiation were used to explore the intervention function and mechanism of AG on obesity. The main results were as follows:3T3-L1preadipocytes were used as the cell model. AG could significantly inhibit the proliferation of preadipocytes, and showed a dose-and time-dependent manner. The half growth inhibitory concentration (IC50) of AG for24h,48h or72h were16.4μg/mL,13.0μg/mL,8.6μg/mL respectively. Dynamic fluorescence visualization technology, molecular probes and other modern molecular cytology technique were used to evaluate the mechanism of AG on the inhibition of preadipocytes. The results showed that AG could induce a special ROS-mediated programmed cell death on3T3-L1preadipocytes. Moreover, we further observed that AG could inhibit adipocyte differentiation, and the inhibition rate of10μg/mL AG significantly reached18.5%, while10μg/mL dose had no toxicity on the differentiating cells. Further studies showed that AG could effectively inhibit the generation of triglycerides in adipocytes, and promote lipolysis. These results indicated that AG could effectively inhibit the proliferation of preadipocytes, the differentiation and adipogenesis of adipocytes, meanwhile promote lipolysis in adipocytes.To evaluate AG’s prevention effect against high fat dietary induced obesity, C57BL/6mice were used in this study. The results indicated that AG had a dramatically reduction on the weight, Lee’s index, food utilization and body fat, in a dose-dependent manner. Low dose (50mg/kg) AG could reduce the weight, body fat and blood glucose; medium dose (100mg/kg) AG could effectively reduce serum TC, TG levels, and improve FFA levels; high dose (150mg/kg) AG could reduce hepatic TC, TG to a certain level, but the FFA levels were not notedly affected. Further studies showed that AG could markedly enhance the total antioxidant capacity of serum, reduce the level of MDA. However, AG had no significant effect on serum SOD activity or liver’s antioxidant capacity.In summary, the results of this research provided an idea and method for studying the intervention efficacies and mechanisms of natural plant functional ingredients on obesity, also provided certain scientific basis of developing AG to a natural, safe and effective product for weight loss.