ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1647921
Association analysis-based screening strategy for quality markers of Tengdan Capsule in the treatment of Hypertensive renal disease
Provisionally accepted
- 1Inner Mongolia Medical University, Hohhot, China
- 2Shaanxi Buchang High-tech Pharmaceutical Co., Ltd.,, Xian, China
- 3The First Clinical Medical College of Inner Mongolia Medical University, Hohhot, China
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Background and Aim: Hypertensive Renal Disease (HRD) is a chronic and progressive condition driven by sustained high blood pressure, which leads to renal fibrosis and, eventually, end-stage kidney failure. Tengdan Capsule (TDC), a traditional Chinese medicinal formulation, has shown therapeutic potential for managing HRD. However, the specific quality markers (Q-markers) responsible for its efficacy and the underlying molecular mechanisms remain insufficiently understood. This study aimed to identify candidate Q-markers of TDC and elucidate the molecular pathways through which it exerts its renoprotective effects, using an integrative association analysisbased approach. Methods: The chemical composition of TDC and its potential Q-markers were systematically characterized through in vitro and in vivo profiling using HPLC-Q-Exactive-MS and chromatographic fingerprinting. Transcriptomic analysis was conducted on angiotensin II-stimulated HEK293T cells to identify differentially expressed genes (DEGs) responsive to candidate Q-markers.Mendelian randomization (MR) analysis based on genome-wide association study (GWAS) data was employed to validate causal genes linked to HRD. Furthermore, untargeted metabolomics was performed to explore metabolic changes associated with transcriptomic targets. Results: A total of 82 chemical constituents were identified in TDC, 51 detected in vivo. Chromatographic fingerprinting across 10 production batches demonstrated high consistency. Integrated analysis of chemical profiling and fingerprint data highlighted Salvianolic acid B (Sal B) as a potential Q-marker.Transcriptomic profiling revealed 210 DEGs enriched in immune and fibrotic pathways. MR analysis identified Killer Cell Lectin Like Receptor D1 (KLRD1) as a protective gene associated with reduced HRD risk (IVW p = 0.00797), with no evidence of horizontal pleiotropy or heterogeneity.Metabolomic profiling identified five key metabolites, among which α,α'-diethyl-3,4,4'-stilbenetriol showed a strong correlation with KLRD1 expression, indicating a potential immune-metabolic regulatory axis. Conclusions: This study presents a novel framework for Q-marker identification in traditional herbal formulations using association-based multi-omics integration. Salvianolic acid B and KLRD1 were key indicators of TDC's quality and efficacy. These findings offer new mechanistic
Keywords: Tengdan Capsule, Hypertensive renal disease, Quality marker, Transcriptomics, Metabolomics
Received: 16 Jun 2025; Accepted: 22 Jul 2025.
Copyright: © 2025 Liu, Li, Zhang, Dong, Wang, Liu, Wang, Zhang and Du. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qian Zhang, The First Clinical Medical College of Inner Mongolia Medical University, Hohhot, China
Xiaoli Du, Inner Mongolia Medical University, Hohhot, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.