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World Journal of Gastrointestinal Oncology
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1948-5204
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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 Gastrointest Oncol. Dec 15, 2026; 18(12): 124725
Published online Dec 15, 2026. doi: 10.4251/wjgo.124725
Weiwikang Formula ameliorates precancerous lesions of gastric cancer: Associations with the HIF-1α/BNIP3 axis, mitophagy, and glycolysis
Xin-Fang Zhang, Guan-Hua Lv, Cheng-Hui Zhu, Shu-Jian An, Xi-Ran Yang
Xin-Fang Zhang, Shu-Jian An, Xi-Ran Yang, Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning Province, China
Guan-Hua Lv, Cheng-Hui Zhu, Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Liaoning Provincial Institute of Traditional Chinese Medicine, Shenyang 110031, Liaoning Province, China
Co-corresponding authors: Guan-Hua Lv and Cheng-Hui Zhu.
Author contributions: Zhang XF performed the experiments, analyzed the data, and wrote the original draft of the manuscript; Lv GH and Zhu CH conceived and designed the study, supervised the project, and critically revised the manuscript as co-corresponding authors; An SJ and Yang XR contributed to the animal experiments and sample collection; all authors have read and approved the final version of the manuscript.
AI contribution statement: The authors take full responsibility and accountability for all content of this manuscript, including any portions for which AI tools were used as assistive technologies. All AI-assisted outputs were carefully reviewed, validated, and approved by the authors. AI tools were not used to generate original scientific data, perform independent scientific analyses, or draw scientific conclusions.
Supported by the Joint Program of the Science and Technology Plan of Liaoning Province (Natural Science Foundation - General Program), No. 2024012225-JH4/4800.
Institutional animal care and use committee statement: All animal procedures were reviewed and approved by the Institutional Animal Care and Use Committee of Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine (approval No. LZYY250203).
Conflict-of-interest statement: The authors declare no conflict of interest in publishing the manuscript.
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: No additional data are available.
Corresponding author: Guan-Hua Lv, PhD, Director, Full Professor, Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Liaoning Provincial Institute of Traditional Chinese Medicine, No. 60 Huanghebei Street, Huanggu District, Shenyang 110031, Liaoning Province, China. 809007025@qq.com
Received: June 23, 2026
Revised: July 29, 2026
Accepted: September 18, 2026
Published online: December 15, 2026
Processing time: 140 Days and 3.8 Hours
Abstract
BACKGROUND

Precancerous lesions of gastric cancer (PLGC) usually arise from chronic gastritis and are associated with an increased risk of gastric cancer. Previous studies have shown that during the progression from chronic gastritis to PLGC, defective mitophagy mediated by the hypoxia-inducible factor 1-alpha (HIF-1α)/B-cell lymphoma 2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) signaling pathway may accelerate PLGC development by inducing excessive reactive oxygen species production, impairing mitochondrial energy metabolism, and promoting glycolysis. Weiwikang Formula (WWKF) is a traditional Chinese medicine formula that has been widely used clinically to treat PLGC. However, the mechanisms underlying its therapeutic effects remain unclear.

AIM

To determine the effects of WWKF on PLGC and associated changes in the HIF-1α/BNIP3 axis, mitophagy, oxidative phosphorylation, and glycolysis.

METHODS

Sixty specific pathogen-free Sprague-Dawley rats underwent N-methyl-N′-nitro-N-nitrosoguanidine-based PLGC modeling and treatment with vitacoenzyme or graded WWKF doses. Clinical indices and hematoxylin and eosin histology were assessed. Immunofluorescence assessed HIF-1α/BNIP3; enzyme-linked immunosorbent assay measured inflammatory/oxidative stress markers. Reverse transcription quantitative polymerase chain reaction and Western blotting quantified HIF-1α, BNIP3, Beclin1, microtubule-associated protein 1 light chain 3, sequestosome 1, cytochrome c oxidase subunit 4, hexokinase 2, and lactate dehydrogenase A.

RESULTS

PLGC model rats exhibited lethargy, reduced body weight, decreased 3-hour food intake, gastric mucosal injury, intestinal metaplasia, and dysplasia. WWKF improved general condition, body weight, and food intake and reduced the extent of histopathological abnormalities, with greater effects at medium and high doses. PLGC rats exhibited increased HIF-1α, sequestosome 1, hexokinase 2, and lactate dehydrogenase A expression and decreased BNIP3, Beclin1, microtubule-associated protein 1 light chain 3-II, and cytochrome c oxidase subunit 4 expression at the mRNA and/or protein levels, forming a molecular pattern consistent with impaired mitophagy-related regulation, reduced oxidative phosphorylation, and enhanced glycolytic activity. WWKF treatment was accompanied by coordinated changes in these markers in the opposite direction. WWKF also reduced serum tumor necrosis factor-α, interleukin-6, interleukin-1β, and malondialdehyde levels and increased superoxide dismutase levels, consistent with attenuation of inflammation and oxidative stress.

CONCLUSION

WWKF ameliorated pathological changes, inflammation, and oxidative stress in PLGC rats, accompanied by coordinated changes in the HIF-1α/BNIP3 axis and markers of mitophagy, oxidative phosphorylation, and glycolysis.

Keywords: Precancerous lesions of gastric cancer; Weiwikang Formula; Hypoxia-inducible factor 1-alpha/B-cell lymphoma 2/adenovirus E1B 19 kDa interacting protein 3 signaling pathway; Mitophagy; Glycolysis

Core Tip: Precancerous lesions of gastric cancer are a pivotal stage in gastric carcinogenesis. In rats, Weiwikang Formula ameliorated gastric mucosal injury, intestinal metaplasia, dysplasia, inflammation, and oxidative stress. These effects were accompanied by coordinated changes in hypoxia-inducible factor 1-alpha, B-cell lymphoma 2/adenovirus E1B 19 kDa interacting protein 3, and molecular markers of mitophagy, oxidative phosphorylation, and glycolysis. These findings highlight a potentially relevant molecular network involving hypoxia-inducible factor 1-alpha/B-cell lymphoma 2/adenovirus E1B 19 kDa interacting protein 3 signaling, mitochondrial quality control, and metabolic remodeling, supporting further investigation of Weiwikang Formula as an intervention for precancerous lesions of gastric cancer.
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