摘要
目的研究腰痹通胶囊(三七、川芎、延胡索,等)治疗腰椎间盘突出的分子作用机制。方法采用文献挖掘、分子对接以及分子-靶蛋白网络特征分析的方法研究腰痹通胶囊中化合物群与靶蛋白的相互作用。结果分子对接发现腰痹通胶囊中有46个活性成分,且大部分具有良好的口服生物利用度和较高的中枢神经暴露量,进一步网络分析发现,其中coptisine、diligustilide、corypalmine、chuanxiongterpene等11个化合物为其主要活性成分,可通过与p38、CGRP、MMPs、TNFα等19个靶蛋白作用,抑制过度性炎症反应和椎间盘内毛细血管浸入,降低神经对刺激的敏感性,调控椎间盘内胶原、蛋白聚糖的代谢平衡,从而缓解疼痛,改善腰椎间盘突出。结论通过网络分析明确了腰痹通胶囊调控腰椎间盘突出的分子作用机制,诠释了其科学内涵,有助于推动后续药效物质基础研究和分子机制实验研究。
AIM To explore analgesic mechanism of Yaobitong Capsules( Notoginseng Radix et Rhizoma,Chuanxiong Rhizoma,Corydalis Rhizoma,etc.) on lumbar intervertebral discs. METHODS An array of data mining,molecular docking and network analysis were employed to investigate the active compounds and key target protein. RESULTS Among the forty-six active hits identified by virtual screening,most compounds displayed good oral bioavailability and might confer an optimal CNS exposure. And eleven molecules( coptisine,diligustilide,corypalmine,chuanxiongterpene,etc.) were further confirmed to alleviate lumbar intervertebral discs through their targeting at nineteen proteins( such as p38,CGRP,MMPs,TNFα) to inhibit the inflammatory response and the infiltration of microvasculature,to reduce the nociceptors sensitivity,and to modulate the balance of Collagen and proteoglycans in catabolic and anabolic responses. CONCLUSION Yaobitong Capsules' clear molecular working mechanism and the key active compounds are revealed by this network-assisted investigation highlight the subsequent experiments on targets and active compounds.
引文
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