The Role of AMPK Signaling in Ulcerative Colitis

Yuyi Yuan,1,* Fang Wang,2,* Xingxing Liu,1,* Bo Shuai,1 Heng Fan1 1Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 2Department of Rehabilitation Medicine, Jingshan Union Hospital, Union Hospital, Huazhong University of Science and Technology, Jingshan, Hubei, 431800, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bo Shuai; Heng Fan, Email bo_shuai@hust.edu.cn; fanheng009@aliyun.comAbstract: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulcer formation of the intestinal mucosa. Due to its high recurrence rate, prolonged course, limited curative options, and significant impact on patients’ quality of life, along with a notable potential for malignant transformation, UC is designated as a refractory global health challenge by the World Health Organization (WHO). The elucidation of the pathogenesis and therapeutic strategies for UC requires further in-depth investigation. AMP-activated protein kinase (AMPK) serves as a central regulator of cellular energy metabolic homeostasis. Emerging evidence indicates that interventions involving traditional Chinese medicine (TCM) components, as well as other pharmacological measures, exert beneficial effects on the intestinal mucosal inflammation and epithelial barrier dysfunction in UC by modulating AMPK signaling, thereby influencing biological processes such as cellular autophagy, apoptosis, inflammatory responses, macrophage polarization, and NLRP3 inflammasome-mediated pyroptosis. The role of AMPK in UC is of significant importance. This manuscript provides a comprehensive overview of the mechanisms through which AMPK is involved in UC, as well as a compilation of pharmacological agents capable of activating the AMPK signaling pathway within the context of UC. The primary objective is to facilitate a deeper comprehension of the pivotal role of AMPK in UC among researchers and clinical practitioners, thereby advancing the identification of novel therapeutic targets for interventions in UC.Keywords: ulcerative colitis, AMPK, colitis-associated biological processes, traditional Chinese medicine monomers