基于中药复方配伍理论探索量效加权在网络药理学研究中的应用——以补肾壮骨汤抗骨质疏松的药效物质和作用机制分析为例

Application of dose-effect weighting in network pharmacology based on compatibility theory of traditional Chinese medicine compound:taking the analysis of pharmacodynamics and action mechanism of Bushen Zhuanggu Decoction against osteoporosis as an example

目的:采用基于中药配伍理论的“量效加权网络药理学”方法初步探寻补肾壮骨汤抗骨质疏松的药效物质和作用机制。方法:采用URLC-Q-TOF-MS分析补肾壮骨汤的化学成分。通过网络药理学方法预测补肾壮骨汤成分靶点与骨质疏松疾病靶点的共有靶点,经PPI分析确定该方核心效应靶点。进而依据复方药味用量比例和成分靶点结合程度对共有靶点进行量效加权,获取加权核心效应靶点。利用Metscape对加权前后的核心效应靶点进行GO功能和KEGG通路分析,分别构建加权前后该方抗骨质疏松的“药味-成分-核心效应靶点-通路”网络。结果:共指认出92个化学成分,分析得到154个成分靶点、4613个疾病靶点以及97个共有靶点,得到TNF、AKT1、EGFR等17个核心效应靶点,其富集的12个化学成分有33.3%源于君臣药味,主要涉及IL-17、PI3K-AKT、TNF等炎症信号通路,解析了“壮骨”机制;而MMP2、ABCB1、CYP19A1等12个加权核心效应靶点,富集的23个化学成分则有69.4%源于君臣药味,在炎症相关通路基础上又富集得到类固醇激素生物合成和雌激素信号通路等,阐释了“补肾”原理。结论:量效加权网络药理学研究更符合中药复方重用君臣药味的配伍理论,更贴近补肾壮骨汤“治肾亦治骨”的中医治则,对探索中药复方的药效物质和作用机制具有一定的参考和指导意义。

OBJECTIVE To explore the pharmacodynamics and action mechanism of Bushen Zhuanggu Decoction against osteoporosis by the method of"dose-effect weighted network pharmacology"based on the theory of compatibility of traditional Chinese medicine.METHODS URLC-Q-TOF-MS was used to analyze the chemical components of Bushen Zhuanggu Decoction.The common targets of component targets and osteoporosis disease targets of Bushen Zhuanggu Decoction were predicted by network pharmacology,and the core effect targets of the prescription were determined by PPI analysis.Then,the common targets were weighted according to the proportion of compound drug dosage and the binding degree of component targets,and the weighted core effect targets were obtained.GO function and KEGG pathway analysis were performed on the core effect targets before and after weighting by Metscape,and the"flavor-component-core effect target-pathway"network of anti-osteoporosis was constructed before and after weighting.RESULTS In this study,a total of 92 chemical components were identified,154 component targets,4613 disease targets and 97 common targets were obtained,17 core effect targets such as TNF,AKT1 and EGFR were obtained,and 33.3%of the 12 chemical components enriched were derived from the flavor of monarch and minister,mainly involving IL-17,PI3K-AKT,TNF and other inflammatory signaling pathways,and the mechanism of"strong bone"was analyzed.Among the 12 weighted core effect targets such as MMP2,ABCB1 and CYP19A1,69.4%of the enriched 23 chemical components were derived from the flavor of monarch and minister.On the basis of inflammation-related pathways,steroid hormone biosynthesis,estrogen signaling pathway,and steroid hormone biosynthesis were enriched,which explained the principle of"tonifying kidney".CONCLUSION The study of dose-effect weighted network pharmacology is more in line with the compatibility theory of Chinese medicine compound reusing monarch and minister medicine,and is closer to the traditional Chinese medicine treatment principle of"treating kidney and bone"of Bushen Zhuanggu decoction,which has certain reference and guiding significance for exploring the pharmacodynamic substances and mechanism of action of Chinese medicine compound.