Laboratory of Molecular Pharmacology, Jilin Provincial Key Laboratory of Biomacromolecules of Chinese Medicine, Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, Jilin, China.
Comb Chem High Throughput Screen. 2022;25(13):2191-2202. doi: 10.2174/1386207325666220221093415.
To explore the molecular mechanism by which Shengmaiyin (Codonopsis pilosula) (SMY) improves isoproterenol (ISO)-induced heart failure (HF) in rats via a traditional Chinese medicine (TCM) integrated pharmacology research platform, The Chinese Medicine Integrated Pharmacology Platform (TCMIP V2.0).
The chemical constituents and drug targets of SMY medicines were identified through TCMIP, and HF disease target information was collected. A prescription Chinese medicinecomponent- core target network was constructed through the TCM network mining module, and biological process and pathway enrichment analyses of core targets were conducted. In vivo experiments in rats were performed to verify the pathway targets. Hematoxylin and eosin staining was used to observe myocardial tissue morphology. ELISA kits were used to detect cAMP content, and Western blotting was used to detect the expression levels of signaling pathway-related proteins.
The TCMIP analysis indicated that SMY treatment of HF activates the GS-β-adrenergic receptor (βAR)-cAMP-protein kinase A (PKA) signaling pathway. The in vivo experimental results confirmed this finding. High-dose SMY significantly improved the morphology of ISO-injured myocardium. The levels of G-protein-coupled receptor (GPCR), adenylate cyclase (AC), βAR, and PKA proteins in myocardial tissue were significantly increased in the SMY group. In addition, the content of cAMP in myocardial tissue was increased, and the content of cAMP in serum was decreased.
Based on the analysis of TCMIP, SMY treatment of HF may activate the GS-βARcAMP- PKA signaling pathway. The findings provide a theoretical basis for further research on the anti-HF mechanism of SMY.
利用中药整合药理学平台（TCMIP V2.0），探讨生脉饮（党参）改善异丙肾上腺素（ISO）诱导的大鼠心力衰竭（HF）的分子机制。
通过 TCMIP 鉴定生脉饮药物的化学成分和药物靶点，并收集 HF 疾病靶点信息。通过 TCM 网络挖掘模块构建方剂中药成分-核心靶点网络，并对核心靶点进行生物过程和通路富集分析。在大鼠体内实验中验证通路靶点。通过苏木精-伊红染色观察心肌组织形态。采用 ELISA 试剂盒检测 cAMP 含量，Western blot 检测信号通路相关蛋白的表达水平。
TCMIP 分析表明，生脉饮治疗 HF 激活了鸟苷酸结合蛋白-β肾上腺素能受体（βAR）-环磷酸腺苷（cAMP）-蛋白激酶 A（PKA）信号通路。体内实验结果证实了这一发现。高剂量生脉饮显著改善 ISO 损伤心肌的形态。SMY 组心肌组织中 G 蛋白偶联受体（GPCR）、腺苷酸环化酶（AC）、βAR 和 PKA 蛋白水平明显升高。此外，心肌组织中环磷酸腺苷（cAMP）含量增加，血清中环磷酸腺苷（cAMP）含量降低。
基于 TCMIP 分析，生脉饮治疗 HF 可能激活 GS-βARcAMP-PKA 信号通路。研究结果为进一步研究生脉饮抗 HF 的机制提供了理论依据。
