Obesity and its associated metabolic disorders such as diabetes, hepatic steatosis and chronic heart diseases are affecting billions of individuals. However there is no satisfactory drug to treat such diseases. In this study, we found that alisol A, a major active triterpene isolated from the Chinese traditional medicine Rhizoma Alismatis, could significantly attenuate high‐fat‐diet‐induced obesity. Our biochemical detection demonstrated that alisol A remarkably decreased lipid levels, alleviated glucose metabolism disorders and insulin resistance in high‐fat‐diet‐induced obese mice. We also found that alisol A reduced hepatic steatosis and improved liver function in the obese mice model.In addition, protein expression investigation revealed that alisol A had an active effect on AMPK/ACC/SREBP‐1c pathway. As suggested by the molecular docking study, such bioactivity of alisol A may result from its selective binding to the catalytic region of AMPK.Therefore, we believe that Alisol A could serve as a promising agent for treatment of obesity and its related metabolic diseases.

Alismatis Rhizoma (zexie), an herb used in traditional Chinese medicine, exhibits hypolipemic, anti-inflammation and anti-atherosclerotic activities. Alisol A is one of the main active ingredients in Alismatis Rhizoma extract. In this study, we investigate the role of alisol A in anti-atherosclerosis (AS). Our study demonstrated that alisol A can effectively inhibit the formation of arterial plaques and blocked the progression of AS in ApoE −/− mice fed with high-fat diet and significantly reduced the expression of inflammatory cytokins in aorta, including ICAM-1, IL-6, and MMP-9. In addition, we found that alisol A increased the expression of PPARa and PPARd proteins in HepG2 cells and in liver tissue from ApoE −/− mice. Alisol A activated the AMPK/SIRT1 signaling pathway and NF-kB inhibitor IkBa in HepG2 cells. Our results suggested that alisol A is a multi-targeted agent that exerts anti-atherosclerotic action by regulating lipid metabolism and inhibiting inflammatory cytokine production. Therefore, alisol could be a promising lead compound to develop drugs for the treatment of AS.

No abstract

Peripheral CB1R blockers without crossing the blood–brain barrier (BBB) have demonstrated therapeutic benefits in metabolic syndromes, including obesity. Among them is Alisol G, a tetracyclic triterpene from Alismatis rhizoma (zexie), which can effectively reduce the weight of obese mice. Results from CP55940-induced [35S] GTPγS cannabinoid-type 1 receptor (CB1R) binding assay show an IC50 of 34.8 μmol/L for Alisol G, implicating its role as a CB1R antagonist. The purpose of our study is to assess whether Alisol G could serve as a peripheral CB1R antagonist for obesity treatment. In this study, we build a simple, reliable, and sensitive method to detect the concentration of Alisol G in rat tissue by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The results showed that Alisol G was mainly distributed in intestinal midgut, mucosa and small intestine, with little brain exposure. We suggested that intestine may be the main acting sites of Alisol G. Through comparison of brain and blood concentrations of Alisol G, our data showed that Alisol G cannot penetrate the BBB easily. In conclusion, Alisol G may represent a peripheral CB1R antagonist for the further treatment of obesity.