GeneNet Pharmaceuticals Co. Ltd., No. 1, Tingjiang West Road, Beichen District, Tianjin, 300410, China.
College of Pharmacy, Nankai University, Haihe Education Park, 38 Tongyan Road, Jinnan District, Tianjin, 300353, China.
Sci Rep. 2021 May 5;11(1):9541. doi: 10.1038/s41598-021-89035-4.
Research on direct targets of traditional Chinese medicine (TCM) is the key to study the mechanism and material basis of it, but there is still no effective methods at present. We took Compound Danshen dropping pills (CDDP) as a study case to establish a strategy to identify significant direct targets of TCM. As a result, thirty potential active kinase targets of CDDP were identified. Nine of them had potential dose-dependent effects. In addition, the direct inhibitory effect of CDDP on three kinases, AURKB, MET and PIM1 were observed both on biochemical level and cellular level, which could not only shed light on the mechanisms of action involved in CDDP, but also suggesting the potency of drug repositioning of CDDP. Our results indicated that the research strategy including both in silico models and experimental validation that we built, were relatively efficient and reliable for direct targets identification for TCM prescription, which will help elucidating the mechanisms of TCM and promoting the modernization of TCM.
中药直接作用靶点的研究是阐明其作用机制和物质基础的关键，但目前仍缺乏有效的方法。我们以复方丹参滴丸（CDDP）为研究案例，建立了一种识别中药显著直接作用靶点的策略。结果，我们鉴定出 30 个潜在的 CDDP 活性激酶靶标，其中 9 个靶标具有潜在的剂量依赖性作用。此外，我们还在生化和细胞水平上观察到 CDDP 对 AURKB、MET 和 PIM1 三种激酶的直接抑制作用，这不仅为 CDDP 作用机制的阐明提供了线索，也提示了 CDDP 药物重定位的潜力。我们的研究结果表明，我们构建的包括计算机模型和实验验证在内的研究策略，对于中药方剂直接作用靶点的鉴定相对高效可靠，这将有助于阐明中药的作用机制，并促进中药的现代化。
