基于神经保护探讨补阳还五汤抗脑缺血损伤的多靶点作用机制

Multi-target neuroprotective effect of Buyang Huanwu Decoction against cerebral ischemia injury

目的利用分子对接技术阐释补阳还五汤在神经保护方面抗脑缺血损伤的多靶点作用机制。方法以补阳还五汤为研究载体,收集各味中药的成分及其代谢产物,选择通过保护神经元从而发挥抗脑缺血损伤的5个谷氨酸受体的7个活性位点为研究对象,利用分子对接技术筛选上述化学成分的潜在活性成分,并分析其作用机制。结果毛蕊异黄酮、刺芒柄花素、川芎哚和芍药新苷等大多数成分可同时作用于2个或2个以上的谷氨酸受体活性位点,体现补阳还五汤通过多成分作用于多靶点、多位点发挥保护神经元抗脑缺血损伤的作用;且大多数成分来源于君药黄芪,少数成分来源于臣药当归尾和佐药川芎、赤芍、红花,与补阳还五汤君臣佐使的配伍原则一致。结论初步揭示补阳还五汤通过多成分作用于多靶点、多位点发挥保护神经元治疗脑缺血损伤的作用机制,为补阳还五汤的临床应用以及实验研究提供了一定的方向,同时也为研究抗脑缺血损伤中药研发提供借鉴。

Objective To explore the multi-target mechanism of neuroprotective effect of Buyang Huanwu Decoction（ BYHWD） against cerebral ischemia injury by using molecular docking. Methods 230 ingredients and metabolites of herbal Chinese medicines of BYHWD were collected and docked with seven active binding sites of five glutamate receptors. The potential anti-cerebral ischemia injury active compounds were screened and the molecular mechanism of the active ingredients was analyzed using molecular docking. Results Calycosin,formononetin,perlolyrine and lactiflorin,main compounds of BYHWD,interacted with two or more binding sites of glutamate receptors,which showed that BYHWD＇s neuroprotective effect against cerebral ischemia in the way of multiple compounds working on multiply targets and multiply sites. Majority of components from the chief drug Radix Astragali（ Huangqi） and minority of components from deputy drug Radix Angelicae Sinensis（ Danggui） and assistant herbs Rhizoma Chuanxiong,Radix Paepmoae Rubra（ Chishao）,and Flos Carthami（ Honghua）,consistent with the combination principles of BYHWD. Conclusion The multi-target neuroprotective effect of BYHWD against cerebral ischemia injury was studied at the molecular level,which can guide the application of BYHWD in clinic. Meanwhile,this study also can provide reference for discovering novel traditional Chinese medicines to treat cerebral ischemia injury.