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.

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.