Multi-omics analysis identifies COX6A2/SCF/c-Kit-mediated mitochondrial remodeling as a key mechanism of Tangwei’an decoction in diabetic gastroparesis

doi:10.3748/wjg.122523

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World Journal of Gastroenterology

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1007-9327

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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 Gastroenterol. Dec 7, 2026; 32(45): 122523
Published online Dec 7, 2026. doi: 10.3748/wjg.122523

Multi-omics analysis identifies COX6A2/SCF/c-Kit-mediated mitochondrial remodeling as a key mechanism of Tangwei’an decoction in diabetic gastroparesis

Yu-Xin Zhang, Xin-Yi Fang, Yan-Jiao Zhang, Rui-Yang Yin, Bin Li, Jia-Xing Tian

Yu-Xin Zhang, Bin Li, Department of Acupuncture and Moxibustion, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing Hospital of Traditional Chinese Medicine, Beijing 100010, China

Yu-Xin Zhang, Xin-Yi Fang, Yan-Jiao Zhang, Rui-Yang Yin, Jia-Xing Tian, Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China

Co-first authors: Yu-Xin Zhang and Xin-Yi Fang.

Co-corresponding authors: Bin Li and Jia-Xing Tian.

Author contributions: Zhang YX contributed to writing - original draft; Fang XY contributed to validation; Zhang YX and Fang XY contributed to visualization and made equal contributions as co-first authors; Zhang YJ contributed to formal analysis and data curation; Yin RY contributed to investigation and methodology; Li B and Tian JX contributed to writing - review & editing and made equal contributions as co-corresponding authors; Tian JX contributed to funding acquisition and formal analysis. All authors approved the final version to publish.

AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.

Supported by GAMIMD Special Fund, No. 2022LYJSZX12; CACMS Outstanding Young Scientific and Technological Talents Program, No. ZZ13-YQ-026; and CACM-PDP Dose-Effect Relationship Research Project, No. 202428-002.

Institutional animal care and use committee statement: All procedures were approved by the Institutional Animal Care and Use Committee of Beijing Pharmacokang Biotechnology Co., Ltd., No. GPT-BJAP20240328-1.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

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: All mass spectrometry data from this study, including proteomics and metabolomics datasets, are publicly available in the OMIX database. The data can be accessed using accession number OMIX008366 for proteomics (https://ngdc.cncb.ac.cn/omix/release/OMIX008366) and OMIX008349 for metabolomics (https://ngdc.cncb.ac.cn/omix/release/OMIX008349).

Corresponding author: Jia-Xing Tian, Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange, Xicheng District, Beijing 100053, China. tina-yai@126.com

Received: April 22, 2026
Revised: June 25, 2026
Accepted: July 13, 2026
Published online: December 7, 2026
Processing time: 176 Days and 22.9 Hours

Abstract

BACKGROUND

Tangwei’an decoction (TWAD) is a traditional Chinese medicinal formula derived from classical prescriptions including Zhizhu Decoction, Xiaobanxia Decoction, and Dahuang Huanglian Xiexin Decoction, and is clinically used for the treatment of diabetic gastroparesis (DGP). However, its pharmacological basis and underlying mechanisms remain unclear.

AIM

To systematically elucidate the bioactive constituents and therapeutic mechanisms of TWAD in DGP using an integrated strategy combining serum pharmacochemistry, integrated proteomics and metabolomics, and in vivo and in vitro experimental validation.

METHODS

Ultra-performance liquid chromatography hybrid quadrupole-Orbitrap high-resolution mass spectrometry was used to investigate the chemical components of TWAD. As a DGP model, db/db mice were given either water or TWAD every day for eight weeks. Integrated proteomics and metabolomics were used to investigate the mechanisms behind TWAD-mediated improvement of gastrointestinal function. Mouse gastric smooth muscle cells were used for complementary in vitro mechanistic validation, and key pathway nodes were verified in both gastric tissue and smooth muscle cell assays.

RESULTS

Ultra-performance liquid chromatography coupled with a hybrid quadrupole-Orbitrap high-resolution mass spectrometer identified 93 constituents in TWAD, and 32 compounds were detected in TWAD-containing serum (9 prototypes and 23 metabolites). In db/db mice with DGP phenotypes, TWAD improved gastric emptying and gastrointestinal motility and attenuated gastric pathological injury, without significantly affecting body weight or fasting glucose. Integrated proteomics and metabolomics consistently prioritized oxidative phosphorylation as the dominant TWAD-responsive pathway, with COX6A2 emerging as a key regulated node. In vivo and gastric smooth muscle cell assays further supported that TWAD modulates mitochondrial dynamics via the COX6A2/SCF/c-Kit axis.

CONCLUSION

TWAD alleviates DGP by restoring mitochondrial dynamics through the COX6A2/SCF/c-Kit signaling pathway. This effect is associated with improved oxidative phosphorylation and gastrointestinal motility in vivo and in vitro, supporting TWAD as a potential therapeutic strategy for DGP.

Keywords: Tangwei’an decoction; Diabetic gastroparesis; Multi-omics; COX6A2/SCF/c-Kit; Mitochondrial dynamics

Core Tip: Tangwei’an decoction (TWAD) is clinically used for diabetic gastroparesis (DGP), but its mechanism remains unclear. This study combined serum pharmacochemistry, integrated proteomics and metabolomics, and experimental validation to show that TWAD alleviates DGP by restoring mitochondrial dynamics. Oxidative phosphorylation was identified as the major pathway regulated by TWAD, with COX6A2 as a key target. TWAD also modulated the SCF/c-Kit axis, providing mechanistic support for its therapeutic potential in DGP.