The Protective Effects of and Tenuifolin on Corticosterone-Evoked Ferroptosis, Oxidative Stress, and Neuroinflammation: Insights from Molecular Dynamics Simulations and In Vitro Experiments

Overview

Journal Foods

Specialty Biotechnology

Date 2024 Nov 9

PMID 39517142

Authors

Chaoyi Xue

Zhiyong He

Maomao Zeng

Zhaojun Wang

Qiuming Chen

Fang Qin

Mingmin Chen

Hui Ye

Jie Chen

Affiliations

Soon will be listed here.

Abstract

Excessive stress is a well-established contributor to neurological damage, insomnia, and depression, imposing a significant burden on individuals and society. This underscores the urgent need for effective stress-relief strategies. The main purpose of this study was to explore the protective effects of (PT) and its bioactive compound, tenuifolin, against corticosterone-induced neurotoxicity, with a focus on ferroptosis, oxidative stress, and neuroinflammation. Both PT extracts and tenuifolin mitigated corticosterone-induced cellular damage. Tenuifolin reversed the corticosterone-induced dysregulation of ferroptosis-associated proteins, such as SLC7A11, GPX4, and Nrf2, leading to a marked reduction in ferroptosis levels. Molecular dynamics simulations revealed that corticosterone significantly altered the conformation and binding energy of the SLC7A11/SLC3A2 complex, critical for ferroptosis regulation. These changes were reversed by tenuifolin. Additionally, tenuifolin alleviated corticosterone-induced oxidative stress and neuroinflammation, both of which accelerated ferroptosis. In conclusion, these results indicate that tenuifolin attenuates corticosterone-induced neurotoxicity by modulating ferroptosis, oxidative stress, and neuroinflammation. This study provides a theoretical foundation for the application of PT and tenuifolin in stress-induced nerve damage.

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