Zhou LJ, Wu JL, Wang H, Han R, Tang C, Fang F, Zhu DP. Integrating proteomics, metabolomics, and molecular docking to elucidate the mechanism of Jiangtang Qingre formula against metabolic dysfunction-associated steatohepatitis. World J Gastroenterol 2026; 32(48): 123033 [DOI: 10.3748/wjg.123033]
Corresponding Author of This Article
Dan-Ping Zhu, Department of Endocrinology and Metabolism, Chongqing Traditional Chinese Medicine Hospital, No. 6 Panxi Qizhi Road, Liangjiang New Area, Chongqing 400021, China. zdp790203@163.com
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Zhou LJ, Wu JL, Wang H, Han R, Tang C, Fang F, Zhu DP. Integrating proteomics, metabolomics, and molecular docking to elucidate the mechanism of Jiangtang Qingre formula against metabolic dysfunction-associated steatohepatitis. World J Gastroenterol 2026; 32(48): 123033 [DOI: 10.3748/wjg.123033]
World J Gastroenterol. Dec 28, 2026; 32(48): 123033 Published online Dec 28, 2026. doi: 10.3748/wjg.123033
Integrating proteomics, metabolomics, and molecular docking to elucidate the mechanism of Jiangtang Qingre formula against metabolic dysfunction-associated steatohepatitis
Li-Juan Zhou, Jin-Lin Wu, Hang Wang, Rui Han, Cai Tang, Fang Fang, Dan-Ping Zhu
Li-Juan Zhou, Jin-Lin Wu, Hang Wang, Rui Han, Cai Tang, Fang Fang, Dan-Ping Zhu, Department of Endocrinology and Metabolism, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China
Co-corresponding authors: Fang Fang and Dan-Ping Zhu.
Author contributions: Zhou LJ, Wu JL, Wang H, Han R, Tang C, Fang F and Zhu DP designed the study; Zhou LJ, Wu JL and Wang H performed the research; Han R and Tang C analyzed the data; Zhou LJ prepared the figures and wrote the manuscript; Fang F and Zhu DP reviewed the manuscript; and all authors have read and approved the final manuscript for submission.
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 Chongqing Clinical Research Center for Metabolic Diseases (Integrated Traditional Chinese and Western Medicine), No. SQMS2025DXB-006, No. SQMS2026DXB-001 and No. SQMS2026DXB-003.
Institutional animal care and use committee statement: The experimental protocol was approved by the Animal Ethics Committee of Chongqing Traditional Chinese Medicine Hospital (Approval No. 2025-DWSY-ZLJ).
Conflict-of-interest statement: All authors confirm that there are no competing interests.
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: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (https://proteomecentral.proteomexchange.org) via the iProX partner repository with the dataset identifier PXD078320. Other data generated and analyzed in this study are available from the corresponding author, Prof. Dan-Ping Zhu (zdp790203@163.com), upon reasonable request.
Corresponding author: Dan-Ping Zhu, Department of Endocrinology and Metabolism, Chongqing Traditional Chinese Medicine Hospital, No. 6 Panxi Qizhi Road, Liangjiang New Area, Chongqing 400021, China. zdp790203@163.com
Received: May 7, 2026 Revised: July 1, 2026 Accepted: September 4, 2026 Published online: December 28, 2026 Processing time: 181 Days and 14.7 Hours
Abstract
BACKGROUND
As the most popular chronic liver disease in the world, one third of metabolic dysfunction-associated steatotic liver disease cases will progress to metabolic dysfunction-associated steatohepatitis (MASH), yet current therapeutic options remain strikingly limited. Jiangtang Qingre formula (JQF) has shown significant clinical efficacy, but the underlying mechanism of it is still not clear.
AIM
To elucidate the mechanism by which JQF ameliorates MASH through integrated multi-omics and experimental validation.
METHODS
The MASH mouse model was constructed using the methionine-choline-deficient diet, and treated with JQF to evaluate its efficacy. Hepatic proteomics and metabolomics were integrated to screen core targets and pathways, and molecular docking was performed to assess the binding affinity between JQF's core components and key targets. Targeted metabolomics quantified these core components in serum, liver, and feces. Finally, the function of key targets was preliminarily validated by quantitative PCR (qPCR)/Western blotting (WB) and small interfering RNA-mediated knockdown in free fatty acids (FFA)-induced AML12 cells.
RESULTS
JQF alleviated hepatic injury, steatosis, oxidative stress, inflammation, and fibrosis in MASH mice. Multi-omics analysis suggested that JQF may act by regulating arachidonic acid metabolism, and glutathione metabolism, involving multiple targets including Gsta2, Gsta5, Ifi27 L2b, and Lmod3, which were validated by qPCR/WB. Notably, knockdown of Lmod3 partially alleviated FFA-induced AML12 cell injury, an effect further augmented by JQF. Molecular docking confirmed that timosaponins exhibited the strongest binding affinity to these targets. Targeted metabolomics further revealed that timosaponin A III and timosaponin B II were significantly elevated in serum and liver, with timosaponin A III showing the most prominent enrichment in the liver, while sarsasapogenin, as the major secondary metabolite of timosaponins, was detected at high abundance in feces.
CONCLUSION
JQF ameliorates MASH through multi-target synergistic mechanisms, with Lmod3 identified as a key target and timosaponins as important pharmacologically active substances.
Core Tip: This study demonstrated that Jiangtang Qingre formula (JQF) ameliorates metabolic dysfunction-associated steatohepatitis through multi-target mechanisms. Multi-omics revealed arachidonic acid metabolism, and glutathione metabolism, with multiple targets implicated including Lmod3. Molecular docking confirmed timosaponins exhibited the strongest binding affinity to these targets. Knockdown of Lmod3 partially alleviated free fatty acids-induced AML12 cell injury, an effect further augmented by JQF. Additionally, timosaponin A III and timosaponin B II were effectively absorbed into the bloodstream and enriched in the liver, while their secondary metabolite sarsasapogenin was detected at high abundance in feces, further supporting the role of timosaponins as key pharmacologically active substances.
