Table2_Exploration of the Mechanism of Salvianolic Acid for Injection Against Ischemic Stroke: A Research Based on Computational Prediction and Experimental Validation.xlsx

Ischemic stroke (IS) is an acute neurological injury that occurs when a vessel supplying blood to the brain is obstructed, which is a leading cause of death and disability. Salvia miltiorrhiza has been used in the treatment of cardiovascular and cerebrovascular diseases for over thousands of years due to its effect activating blood circulation and dissipating blood stasis. However, the herbal preparation is chemically complex and the diversity of potential targets makes difficult to determine its mechanism of action. To gain insight into its mechanism of action, we analyzed “Salvianolic acid for injection” (SAFI), a traditional Chinese herbal medicine with anti-IS effects, using computational systems pharmacology. The potential targets of SAFI, obtained from literature mining and database searches, were compared with IS-associated genes, giving 38 common genes that were related with pathways involved in inflammatory response. This suggests that SAFI might function as an anti-inflammatory agent. Two genes associated with inflammation (PTGS1 and PTGS2), which were inhibited by SAFI, were preliminarily validated in vitro. The results showed that SAFI inhibited PTGS1 and PTGS2 activity in a dose-dependent manner and inhibited the production of prostaglandin E2 induced by lipopolysaccharide in RAW264.7 macrophages and BV-2 microglia. This approach reveals the possible pharmacological mechanism of SAFI acting on IS, and also provides a feasible way to elucidate the mechanism of traditional Chinese medicine (TCM).

缺血性脑卒中（Ischemic stroke, IS）是一种急性神经系统损伤，当脑部供血血管发生阻塞时即会发病，也是致死与致残的首要病因之一。丹参（Salvia miltiorrhiza）因其具有活血化瘀的功效，已被用于心脑血管疾病的治疗长达千余年。然而该中药制剂化学成分复杂，潜在作用靶点繁多，故而其作用机制难以明确。为深入解析其作用机制，本研究采用计算系统药理学方法，对具有抗缺血性脑卒中活性的中药制剂——注射用丹酚酸（Salvianolic Acid for Injection, SAFI）展开分析。通过文献挖掘与数据库检索获取SAFI的潜在作用靶点，并将其与缺血性脑卒中相关基因进行比对，最终得到38个与炎症反应通路相关的共有基因。这提示SAFI可能通过发挥抗炎作用实现其药效。本研究针对SAFI抑制的两个炎症相关基因（PTGS1、PTGS2）开展了体外初步验证。实验结果显示，SAFI可呈剂量依赖性抑制PTGS1与PTGS2的活性，并能在RAW264.7巨噬细胞与BV-2小胶质细胞中，抑制脂多糖诱导的前列腺素E2生成。本研究方法不仅揭示了SAFI治疗缺血性脑卒中的潜在药理机制，同时也为阐明中药（Traditional Chinese Medicine, TCM）的作用机制提供了可行的研究路径。