(-)-Epigallocatechin gallate alleviates chronic unpredictable mild stress-induced depressive symptoms in mice by regulating the mTOR autophagy pathway and inhibiting NLRP3 inflammasome activation

Yulin Zhang; Hongxian Wu; Chaozhi Xu; Shanqian Li; Yue Hu; Zongyi Zhang; Guixian Wu; Yuling Liu; Lin Yang; Yue Huang; Wenjun Lu; Lina Hu

doi:10.1002/fsn3.3761

(-)-Epigallocatechin gallate alleviates chronic unpredictable mild stress-induced depressive symptoms in mice by regulating the mTOR autophagy pathway and inhibiting NLRP3 inflammasome activation

Food Sci Nutr. 2023 Oct 30;12(1):459-470. doi: 10.1002/fsn3.3761. eCollection 2024 Jan.

Authors

Yulin Zhang^{1

2}, Hongxian Wu³, Chaozhi Xu⁴, Shanqian Li^{1

5

6}, Yue Hu⁷, Zongyi Zhang⁸, Guixian Wu^{1

5

6}, Yuling Liu^{1

5

6}, Lin Yang^{1

5

6}, Yue Huang⁹, Wenjun Lu¹⁰, Lina Hu^{1

5

6}

Affiliations

¹ School of Public Health Guilin Medical University Guilin China.
² Department of Nutrition Second People's Hospital of Ya'an City Ya'an City Sichuan Province China.
³ Department of Cardiology, Zhongshan Hospital Shanghai Institute of Cardiovascular Diseases, Fudan University Shanghai China.
⁴ Medical Information Management, School of Humanities and Management Guilin Medical University Guilin China.
⁵ Guangxi Key Laboratory of Environmental Exposomics and Whole Life Cycle Health Guilin China.
⁶ Key Cultivation Laboratory of Life Cycle Health Care Research Guilin China.
⁷ Institute of Drug Inspection Technology Shanxi Inspection and Testing Center Taiyuan Shanxi Province China.
⁸ Communicable Disease Control Branch Qingdao City Center for Disease Control and Prevention Qingdao China.
⁹ Department of Pediatrics The First Affiliated Hospital of Guangxi Medical University Nanning China.
¹⁰ General Practice Department Affiliated Hospital of Guilin Medical University Guilin China.

Abstract

Depression is a global public health issue that is widely studied due to the large number of people it affects and its serious consequences. Clinical studies have shown that regular tea consumption may reduce depression risk. (-)-Epigallocatechin gallate (EGCG), the main tea polyphenol, was observed to alleviate depression, but the underlying mechanism has not been elucidated. In this study, chronic unpredictable mild stress (CUMS) was used to induce depression-like behavior in mice, and behavioral tests, such as sucrose preference test and forced swim test, were performed. Then, ELISA, western blot and QT-PCR tests were used to assess the expression of the key components of the NLRP3 inflammasome and its downstream inflammatory effectors (e.g., IL-1β, IL-18), autophagy markers (Beclin-1, LC3, P62) and apoptosis markers (Bax, Bcl-2) in mouse brain tissues. Changes in serum lipid levels were also assessed. EGCG alleviated CUMS-induced depression-like behavioral changes in mice, reduced activation of the NLRP3 inflammasome, inhibited the mTOR signaling pathway, restored autophagy levels, reduced apoptosis marker expression and attenuated abnormal changes in blood lipid levels. Our study demonstrates that EGCG exerts antidepressive effects through multiple mechanisms, providing new insight into the pathological mechanism of depression and laying the foundation for the development of new therapeutic measures.

Keywords: EGCG; apoptosis; autophagy; chronic unpredictable stress; depression; inflammation.