中文摘要
肥胖是当今人类所面临的严峻挑战,仍缺乏安全、有效的治疗药物。肥胖的直接病因是机体能量代谢失衡,而肠道菌是宿主能量代谢平衡的重要调节者。肠道菌群失调与中医学的脾气虚证具有高度的相关性,后者也是肥胖的重要病机,因而形成了肥胖的‘肠道菌群失调、能量代谢失衡与脾气虚证’三种紧密依存的特征。根据肥胖的‘从脾论治’中医思想,我们依据报道的防己黄芪汤的临床减肥证据,验证了该复方,及黄芪水提物与黄芪多糖(APS)的减肥作用,并观察到APS的减肥作用与调节肠道菌有关。本项目将重点研究APS通过肠道菌,调节宿主能量代谢,发挥减肥作用的机理,提出 “APS-肠道菌-菌群代谢物-能量代谢”关系轴假说。该研究将揭示肠道菌介导APS调控宿主能量代谢分子网络的机理,并将为其它植物多糖作用机理的研究,以及在防治肥胖的产品开发上提供科学依据,促进对健脾益气类中药药效与调控肠道菌关系的认识, 丰富中医脾气虚证的现代科学内涵。
英文摘要
Obesity is one of the most challenges in the 21st century. However, we are still lacking safe and effective anti-obesity drugs to date. Obesity is directly caused by imbalance of energy metabolism, and gut microbiota plays important role in modulating host energy homeostasis. Meanwhile, the dysreguation of gut microbiota is highly correlated with Spleen-qi deficiency syndrome, which is regarded as the main pathogenesis of obesity in TCM. As a result, obesity is characterized by three inter-correlated properties, i.e dysregulation of gut microbiota, imbalance in energy metabolism, and Spleen-qi deficiency syndrome. According to the theory of ‘obesity treatment by targeting on Spleen’ in TCM, and the clinical anti-obesity evidence of Fangji Huangqi Decoction, a classical TCM formula, we first validated the anti-obesity effect of Fangji Huangqi Decoction and its main component, the aqueous extract of Huangqi, and Astraglus polysaccharides (APS), the main effective part of Huangqi. Our results indicated that both the whole formula and the aqueous extract of Huangqi had similar anti-obesity effect in high-fat diet fed mice. Moreover, our results indicated that the anti-obesity effect of APS was associated with modulation on gut microbiota in mice. In the current project, our principal objective is to elucidate the underlying mechanism of the anti-obesity effect of APS. Based on our preliminary results, we hypothesized the axis of “APS-gut microbiota-microbial metabolites-energy metabolism” underlying the anti-obesity effect of APS. This study will not only reveal the anti-obesity mechanism of APS by modulating gut microbiota and host energy metabolism homeostasis, but also highlight the importance of gut microbiota in modulating host metabolism of other herb-derived polysaccharides, provide scientific evidence for research and development of herb-derived polysaccharides in obesity therapy. It will also identify the relationship between gut microbiota and activity of traditional medicines with invigorating Spleen and supplementing Qi character, as well as enriching the scientific content of Spleen-qi deficiency syndrome in TCM.
