Alisol A Alleviates Arterial Plaque by Activating AMPK/SIRT1 Signaling Pathway in apoE-Deficient Mice.

A lismatis 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 PPARα and PPARδ proteins in HepG2 cells and in liver tissue from ApoE-/- mice. Alisol A activated the AMPK/SIRT1 signaling pathway and NF-κB inhibitor IκBα 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.

Alisol A attenuates high-fat-diet-induced obesity and metabolic disorders via the AMPK/ACC/SREBP-1c pathway.

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.

Simultaneous determination of three triterpenes in rat plasma by LC-MS/MS and its application to a pharmacokinetic study of Rhizoma Alismatis extract.

We have developed a sensitive and specific LC-MS/MS method for the simultaneous determination of alisol A (A), alisol A 23-acetate (A23) and alisol A 24-acetate (A24), the major active components in Rhizoma Alismatis extract (RAE), in rat plasma. In brief, plasma samples were extracted by methyl tert-butyl ether and chromatographically separated by using a C18 column. A tandem mass spectrometric detection with an electrospray ionization (ESI) interface was conducted via multiple reaction monitoring (MRM) under positive ionization mode. This method was validated for specificity, linearity, accuracy (within ±15.4%), intra- and inter-day precision (CV<11.4%) over the concentration range of 25-5000ng/mL for A, and 5-1000ng/mL for both A23 and A24. The significantly lower detection limit was determined as 25ng/mL for A, 5ng/mL for A23 and A24. This validated method of ours was then used to study the pharmacokinetics of RAE in rat. The elimination half-lives (t1/2) of A, A23 and A24 was determined as 0.75, 0.83 and 0.82h respectively after intravenous injection, and the oral absolute bioavailability of A, A23 and A24 was 43.1±18.1%, 6.3±1.5% and 7.9±1.2%. This new determination method of us for alisols is proven to very useful to study the pharmacological activities of RAE in future.