延胡索及金铃子散镇痛的药效学和网络药理学比对研究

延胡索与金铃子散均为抗炎镇痛药,金铃子散为川楝子与延胡索组成的中药复方。为比对研究延胡索及金铃子散镇痛作用的差异,通过小鼠热板法和扭体法实验比对两者的药效作用。通过网络药理学构建“成分-靶点-通路”网络,筛选出关键活性成分、核心靶点基因和关联度较高的信号通路。通过虚拟分子对接技术验证关键活性成分和核心靶点的亲和力。小鼠热板法和扭体法实验结果表明：延胡索与金铃子散在给药后60 min内镇痛效果相似;在60 min后,金铃子散的痛阈值提高率显著高于延胡索。延胡索与金铃子散的网络药理学结果相似,活性成分主要来源于延胡索：四氢小檗碱、延胡索碱、延胡索甲素、延胡索乙素、唐松草坡芬碱;通过调节PTGS2、SLC6A4、COMT、DRD4、TH等蛋白的表达作用于神经活性配体受体相互作用、钙离子信号通路和5-羟色胺能突触等相关通路达到镇痛效果。分子对接结果显示,5个关键活性成分与9个核心靶点均有较强的对接活性。研究结果提示延胡索与金铃子散都具有很好地镇痛作用,且金铃子散镇痛作用更长久;延胡索和金铃子散镇痛的网络药理学结果相似,且均体现了多成分、多靶点和多途径的特点。

Comparative study on pharmacodynamics and network pharmacology of Yanhusuo and Jinlingzi powder for analgesia

Yanhusuo and Jinlingzi powder are both anti-inflammatory and analgesic drugs. Jinlingzi powder is a traditional Chinese medicine compound composed of Chuanlianzi and Yanhusuo. In order to compare the analgesic effects of Yanhusuo and Jinlingzi powder, the hot plate and twisting body methods were used in mice to compare the pharmacodynamics of Yanhusuo and Jinlingzi powder. A "Compound-Target-Pathway" network was constructed to screen out the key active compounds, core targets and important related signaling pathways by network pharmacology. The affinity of key active compounds and core targets was verified by virtual molecular docking. The experimental results of hot plate and twisting body methods in mice showed that the analgesic effects of Yanhusuo and Jinlingzi powder were similar within 60 minutes after administration. After 60 minutes, the increase rate of pain threshold of Jinlingzi powder was significantly higher than that of Yanhusuo. The results of network pharmacology of Yanhusuo and Jinlingzi powder were similar. The active compounds were mainly from Yanhusuo: Canadine, Capaurine, Corydaline, Rotundine and Thaliporphine. The expression of PTGS2, SLC6A4, COMT, DRD4, TH and other proteins were regulated, then the analgesic effect could be achieved by acting on the neuroactive ligand-receptor interaction, calcium signaling pathway, serotonergic synapse and other related pathways. The results of molecular docking showed that there was a strong affinity between the five key active compounds and nine core targets. It indicated that both Yanhusuo and Jinlingzi powder had great analgesic effect, and Jinlingzi powder had a longer analgesic effect than Yanhusuo. The network pharmacology results of Yanhusuo and Jinlingzi powder for analgesia were similar, and showed the characteristics of multiple compounds, multiple targets and multiple pathways.