Department of Natural Medicinal Chemistry, College of Pharmacy, Second Military Medical University, Shanghai, China.
PLoS One. 2012;7(9):e44938. doi: 10.1371/journal.pone.0044938. Epub 2012 Sep 17.
Astragaloside IV (AGS-IV) is a main active ingredient of Astragalus membranaceus Bunge, a medicinal herb used for cardiovascular diseases (CVD). In this work, we investigated the therapeutic mechanisms of AGS-IV at a network level by computer-assisted target identification with the in silico inverse docking program (INVDOCK). Targets included in the analysis covered all signaling pathways thought to be implicated in the therapeutic actions of all CVD drugs approved by US FDA. A total of 39 putative targets were identified. Three of these targets, calcineurin (CN), angiotensin-converting enzyme (ACE), and c-Jun N-terminal kinase (JNK), were experimentally validated at a molecular level. Protective effects of AGS-IV were also compared with the CN inhibitor cyclosporin A (CsA) in cultured cardiomyocytes exposed to adriamycin. Network analysis of protein-protein interactions (PPI) was carried out with reference to the therapeutic profiles of approved CVD drugs. The results suggested that the therapeutic effects of AGS-IV are based upon a combination of blocking calcium influx, vasodilation, anti-thrombosis, anti-oxidation, anti-inflammation and immune regulation.
黄芪甲苷（AGS-IV）是中药黄芪的主要活性成分，用于治疗心血管疾病（CVD）。在这项工作中，我们通过计算机辅助的反向对接程序（INVDOCK）对目标进行鉴定，从网络层面研究了 AGS-IV 的治疗机制。分析中包括的靶点涵盖了所有被认为与美国食品和药物管理局批准的所有 CVD 药物的治疗作用有关的信号通路。共鉴定出 39 个潜在靶点。其中三个靶点，钙调神经磷酸酶（CN）、血管紧张素转换酶（ACE）和 c-Jun N-末端激酶（JNK），在分子水平上得到了实验验证。在阿霉素处理的培养心肌细胞中，还将 AGS-IV 的保护作用与 CN 抑制剂环孢素 A（CsA）进行了比较。通过参考已批准 CVD 药物的治疗谱，对蛋白质-蛋白质相互作用（PPI）网络进行了分析。结果表明，AGS-IV 的治疗作用基于阻断钙内流、血管舒张、抗血栓形成、抗氧化、抗炎和免疫调节的联合作用。
