Modified Tou Nong Powder obstructs ulcerative colitis by regulating autophagy and mitochondrial function

Linzhen Li; Zhen Ye; Huanzhu Qian; Liulin Chen; Yu Hu; Xiaolan Liu; Jinyu Zhu; Taozhi Bao; Kumar Ganesan; Fating Lu; Juan Wang; Xudong Wen; Kaihua Qin; Qiaobo Ye

doi:10.1016/j.jep.2024.119220

Modified Tou Nong Powder obstructs ulcerative colitis by regulating autophagy and mitochondrial function

J Ethnopharmacol. 2024 Dec 5:340:119220. doi: 10.1016/j.jep.2024.119220. Online ahead of print.

Authors

Linzhen Li¹, Zhen Ye¹, Huanzhu Qian¹, Liulin Chen¹, Yu Hu¹, Xiaolan Liu², Jinyu Zhu², Taozhi Bao³, Kumar Ganesan⁴, Fating Lu¹, Juan Wang⁵, Xudong Wen⁶, Kaihua Qin⁷, Qiaobo Ye⁸

Affiliations

¹ School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
² Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
³ School of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
⁴ School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
⁵ School of Public Health Chengdu University of TCM, Chengdu, China.
⁶ Chengdu Integrated Traditional Chinese Medicine & Western Medicine Hospital, Chengdu, China.
⁷ Health Preservation and Rehabilitation College, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: qkh0135@163.com.
⁸ School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China. Electronic address: yeqiaobo@cdutcm.edu.cn.

PMID: 39645099
DOI: 10.1016/j.jep.2024.119220

Abstract

Ethnopharmacological relevance: Modified Tou Nong Powder (MTNP) is a traditional Chinese medicine formula widely used for treating body surface ulcers. Since colonic ulcers share similar pathological characteristics, MTNP has shown promising results in alleviating ulcerative colitis (UC) and has been safely used in clinical practice.

Aim of the study: This study aims to investigate how MTNP alleviates experimental colitis by inducing autophagy through the regulation of the AMP-activated protein kinase (AMPK)/Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signaling pathway.

Materials and methods: In this study, UC rat models were created using 2,4,6-Trinitrobenzenesulfonic acid (TNBS). The therapeutic effects of MTNP on TNBS-induced colitis were evaluated through various methods such as disease activity index, visual examination, and histological examination of the colon. An inflammation model was also established in Caco-2 cells using H₂O₂. Western blot analysis was used to assess the expression of autophagy-related proteins, while immunofluorescence detection was employed for protein localization. Furthermore, quantitative real-time polymerase chain reaction (qPCR) was performed to analyze the expression of autophagy-related genes, confirming the role of MTNP in modulating the AMPK/PGC-1α signaling pathway.

Results: In vivo, oral administration of MTNP led to a remarkable reduction in colonic injury, inhibition of inflammatory infiltration, and improvement in the abnormal expression of inflammatory factors in colonic tissues. Furthermore, MTNP stimulated autophagy by activating the AMPK/PGC-1α signaling pathway, thereby mitigating mitochondrial dysfunction. In vitro, exposure to MTNP drug-containing serum (MTNP-DS) resulted in a reduction of reactive oxygen species levels, improvement in mitochondrial membrane potential, and activation of the AMPK/PGC-1α pathway, leading to the promotion of mitochondrial autophagy.

Conclusion: The results indicate that MTNP triggers autophagy and enhances mitochondrial function, leading to the alleviation of UC in both in vitro and in vivo. These benefits are strongly linked to the activation of the AMPK/PGC-1α signaling pathway.