Shenqi Jiangtang Granules attenuate ferroptosis in diabetic cardiomyopathy via the dihydroorotate dehydrogenase-coenzyme Q pathway

doi:10.4239/wjd.117524

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World Journal of Diabetes

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1948-9358

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Diabetes. Jun 15, 2026; 17(6): 117524
Published online Jun 15, 2026. doi: 10.4239/wjd.117524

Shenqi Jiangtang Granules attenuate ferroptosis in diabetic cardiomyopathy via the dihydroorotate dehydrogenase-coenzyme Q pathway

Yi-Ting Tang, Yu-Peng Chen, Ya-Nan Yang, Jun-Li Liu, Qian Wu, Shan Zhang, Qing Pang, Mao-Ying Wei, Yan-Bing Gong, Qing Ni

Yi-Ting Tang, Graduate College, Beijing University of Chinese Medicine, Beijing 100029, China

Yi-Ting Tang, Mao-Ying Wei, Yan-Bing Gong, Department of Nephrology and Endocrinology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China

Yi-Ting Tang, Jun-Li Liu, Division of Endocrinology and Metabolism, Department of Medicine, McGill University, Montreal H4A 3J1, Quebec, Canada

Yu-Peng Chen, Ya-Nan Yang, Qian Wu, Shan Zhang, Qing Pang, Qing Ni, Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China

Co-first authors: Yi-Ting Tang and Yu-Peng Chen.

Author contributions: Tang YT and Chen YP contributed equally to this study as co-first authors; Tang YT, Chen YP and Yang YN drafted the manuscript; Tang YT performed the methodology, investigation and visualization; Chen YP performed data curation and validation; Yang YN performed formal analysis and assisted with visualization; Liu JL and Wei MY provided resources and supervised the study; Wu Q, Zhang S and Pang Q contributed to the investigation and data analysis (including software analysis); Gong YB and Ni Q conceived and designed the study; Ni Q administered the project; Wei MY, Gong YB and Ni Q acquired funding; Ni Q revised the manuscript; all authors have read and approved the final manuscript.

AI contribution statement: Neither the entirety nor any portion of the scientific content of the Main Text, including the Abstract, Introduction, Materials and Methods, Results, Discussion, and Conclusion, was AI-generated. The study design, experimental procedures, data analysis, interpretation of results, and scientific conclusions were developed, performed, verified, and approved by the authors. ChatGPT and Grammarly were used for grammar correction and language polishing. However, AI tools were not used for data analysis nor for generating original scientific content. AI tools were not used in the design of the study or the interpretation of its results. No images, figures, tables, or graphical data in the manuscript were generated by AI.

Supported by the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation, No. GZC20230324; China Postdoctoral Science Foundation, No. 2024M750263; the Leading Talent Training Program Project of Dongzhimen Hospital, Beijing University of Chinese Medicine, No. DZMG-LJRC0004; the Fundamental Research Funds for the Central Universities, No. 2023-JYB-JBZD-010; the High-Level Chinese Medical Hospital Promotion Project, No. HLCMHPP2023084; and the National Key R&D Program of China, No. 2024ZD0523503.

Institutional animal care and use committee statement: The animal study was reviewed and approved by the Medical and Laboratory Animal Ethics Committee of Beijing Institute of Traditional Chinese Medicine (Approval No. BUCM-2023020604-1150).

Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: Data will be made available on request.

Corresponding author: Qing Ni, PhD, Professor, Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange, Xicheng District, Beijing 100053, China. niqing2834@gamyy.cn

Received: December 12, 2025
Revised: February 16, 2026
Accepted: April 8, 2026
Published online: June 15, 2026
Processing time: 184 Days and 8.4 Hours

Abstract

BACKGROUND

Shenqi Jiangtang Granules (SQJT), a traditional Chinese patent medicine, have long been prescribed for type II diabetes mellitus. Increasing evidence suggests that SQJT has cardioprotective effects; however, its mechanisms in diabetic cardiomyopathy (DCM), particularly regarding ferroptosis, remain unclear. We hypothesized that SQJT protects against DCM by inhibiting ferroptosis via the dihydroorotate dehydrogenase (DHODH)/coenzyme Q (CoQ) signaling pathway.

AIM

To elucidate the mechanism through which SQJT attenuates ferroptosis in DCM.

METHODS

Active constituents of SQJT were obtained from previous mass spectrometry analyses. Potential targets were predicted using network pharmacology, protein-protein interaction, molecular docking, and dynamics simulation. Cell viability, death, and ferroptosis markers were assessed in high glucose/lipid-induced H9C2 cells. Intracellular iron, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH), and reactive oxygen species (ROS) levels were measured, and mitochondrial morphology was examined by MitoTracker staining. The expression of DHODH/CoQ pathway components was analyzed by reverse transcription-quantitative PCR and Western blotting, and pathway dependence was confirmed using the DHODH inhibitor brequinar (BRQ).

RESULTS

The SQJT-DCM-ferroptosis network identified 16 intersecting targets, with DHODH as the primary candidate. SQJT significantly improved cell viability and attenuated ferroptosis. Specifically, treatment with 6% SQJT reduced intracellular free iron levels by 61.8% and lipid peroxidation (MDA) levels by 55.9% (all P < 0.001). Furthermore, SQJT restored antioxidant enzyme activities (SOD and GSH-PX) by over 100%, while maintaining mitochondrial membrane integrity and reducing the proportion of ROS-positive cells from 51.6% to 11.8%. These protective effects, mediated via the DHODH/CoQ signaling axis, were significantly abolished by BRQ.

CONCLUSION

SQJT alleviates ferroptosis and oxidative stress, potentially through modulation of the DHODH/CoQ pathway, while preserving mitochondrial integrity and enhancing cardiomyocyte survival, suggesting its therapeutic potential in DCM. However, the mechanistic findings were based on pharmacological inhibition rather than genetic validation. Therefore, further genetic and in vivo studies are needed.

Keywords: Shenqi Jiangtang Granules; Diabetic cardiomyopathy; Ferroptosis; DHODH/CoQ pathway; Oxidative stress

Core Tip: This study investigates the mechanisms of Shenqi Jiangtang Granules (SQJT) against diabetic cardiomyopathy (DCM). By integrating network pharmacology and experimental validation, we identified dihydroorotate dehydrogenase (DHODH) as a key therapeutic target. We demonstrate that SQJT mitigates ferroptosis and mitochondrial injury in H9C2 cardiomyocytes by activating the DHODH/coenzyme Q axis. These protective effects are significantly abolished by DHODH inhibition. This research provides mechanistic evidence that SQJT exerts cardioprotective effects through ferroptosis regulation and highlights its potential as a therapeutic strategy for mitochondrial dysfunction in DCM.