a Department of Comparative medicine, Dalian Medical University, Dalian, Liaoning, 116044, China;
b Department of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China;
c St. Hilda's College, Oxford University, Oxford, OX4 1DY, UK
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This work was financially supported by the National Science Foundation of China (Grant Nos.: U23A20516, 82273897, and 82141203), the Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine, China (Grant No.: 2023YZZ02), Shanghai Municipal Health Commission's Traditional Chinese Medicine Research Project, China (Grant No.: 2022CX005), the Shanghai Science and Technology Innovation Action Plans of the Shanghai Science and Technology Committee, China (Grant No.: 21S21900600), the Three-year Action Plan of the Shanghai Traditional Chinese Medicine Development and Inheritance Program, China (Program No.: ZY (2021-2023)-0401), and the Basic Scientific Research Project of Liaoning Province Education Department, China (Project No.: LJKZ0832).
Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, and has become a major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC. This review covers the pathogenesis of IBD and CRC, focusing on mitochondrial dysfunction, and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function. Additionally, recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC, encompassing mitochondrial damage, release of mitochondrial DNA (mtDNA) and impairment of mitophagy are thoroughly summarized. The review also provides a comprehensive overview of various natural compounds (such as flavonoids, alkaloids, and diterpenoids), Chinese medicines, and intestinal microbiota which can alleviate IBD and retarding the progression of CRC by modulating mitochondrial function. In the future, it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function, which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.
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