[Unveiling efficacy targets and differentiated mechanisms of Colquhounia Root Tablets in "homotherapy for heteropathy" of rheumatoid arthritis and diabetic kidney disease: a analysis based on topological feature identification and path priority assessment].

Authors

Bing-Bing Cai, Xia Mao, Zhao-Chen Ma, Ming-Zhu Xu, Ya Lin, Na Lin, Yan-Qiong Zhang

Published in

Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. Volume 51. Issue 11. Pages 3284-3293.

Abstract

Based on a strategy integrating topological feature identification and path priority assessment, this study systematically explored the efficacy targets and differentiated mechanisms of Colquhounia Root Tablets(CRT) in the "homotherapy for heteropathy" of rheumatoid arthritis(RA) and diabetic kidney disease(DKD). Firstly, candidate targets of CRT and disease-specific genes were retrieved by integrating multi-source databases and transcriptomic data. Protein-protein interaction(PPI) networks were constructed to identify key targets shared by or specific to RA and DKD via topological feature identification. Subsequently, a path priority assessment was introduced to calculate the average shortest path(ASP) values from drug targets to various pathological segments, thereby quantifying intervention efficacy to lock onto "dominant pharmacodynamic links". The predicted key functional axes were validated through animal experiments. The results indicated that the core targets of CRT for both diseases involved shared pathways such as phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt), tumor necrosis factor(TNF), and glycolysis/gluconeogenesis. Notably, path priority assessment revealed distinct dominant intervention links: for RA, CRT preferentially targeted "fibroblast-like synoviocyte(FLS) activation and invasion"(ASP=2.361), which mapped to the TNF-p38 mitogen-activated protein kinase(p38)-LIM domain kinase 1(LIMK1)-Cofilin1 axis to regulate cytoskeleton remodeling; for DKD, the dominant link was "filtration barrier injury and interstitial fibrosis"(ASP=2.295), converging on the TNF-poly(ADP-ribose) polymerase 1(PARP1)-signal transducer and activator of transcription 1(STAT1)-matrix metallopeptidase 9(MMP9) axis to mediate cellular senescence and senescence-associated secretory phenotype(SASP) secretion. Animal experiments confirmed that CRT significantly alleviated RA synovial invasion and DKD renal fibrosis by inhibiting these two differentiated signaling axes, respectively. By employing topological feature identification and path priority assessment, this study elucidates the scientific connotation of "homotherapy for heteropathy" of RA and DKD with CRT through both shared network regulation and intervention in disease-specific differential signaling axes associated with pharmacodynamic links.

PMID:
42543287
Bibliographic data and abstract were imported from PubMed on 03 Aug 2026.

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