Baicalin attenuates corticosterone-induced hippocampal neuronal injury by activating mitophagy in an AMPK-dependent manner.

Autor: Liu Y; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan Province, 450046, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, China; College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China., Jin X; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan Province, 450046, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, China; College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China., Li C; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan Province, 450046, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, China; College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China., Bu J; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan Province, 450046, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, China; College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China., Wang B; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan Province, 450046, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, China., Bai M; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan Province, 450046, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, China., Su P; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan Province, 450046, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, China. Electronic address: Supan@hactcm.edu.cn., Xu E; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan Province, 450046, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, China. Electronic address: Xuerping@hactcm.edu.cn., Li Y; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan Province, 450046, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, China. Electronic address: Liyucheng@hactcm.edu.cn.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Dec 15; Vol. 985, pp. 177091. Date of Electronic Publication: 2024 Nov 09.
DOI: 10.1016/j.ejphar.2024.177091
Abstrakt: Defective mitophagy is closely related to the neuronal dysfunction and major depressive disorder (MDD). Our previous study found that baicalin could enhance nip-like protein (NIX)-mediated mitophagy and exhibit antidepressant effects, and predicted that AMPK may be the pharmacological target of baicalin. However, validated experiments are lacking. In the present study, we first demonstrated the effect of baicalin on hippocampal NIX-mediated mitophagy in CORT-induced depressive mice. Secondly, we transfected siRNA to knockdown AMPK, PGC-1α, and NIX respectively in HT22 cells, and detected the effects of baicalin on mitochondrial function, AMPK/PGC-1α/NIX pathway protein expression and mitophagy levels. Finally, AAV-shAMPKα was injected into hippocampal CA3 to knockdown AMPK in mice to validate the antidepressant effects of baicalin in vivo. The results showed that CORT induced depressive-like behaviors, accompanied with neuronal damage, mitochondrial injury, and inhibited mitophagy in the hippocampus, which were prevented by baicalin (20 mg/kg) treatment. In HT22 cells, baicalin remarkably ameliorated mitochondrial dysfunction and mitophagy disturbance induced by CORT, and these protective effects of baicalin were blocked by knockdown of AMPK, PGC-1α and NIX. Moreover, the beneficial effects of baicalin on depressive-like behaviors and NIX-mediated mitophagy were suppressed by knockdown of AMPKα in mice. Our present results further demonstrated that baicalin promotes NIX-mediated mitophagy and improves depression in an AMPK-dependent manner.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: