Xinglou Chengqi Decoction Protects against Cerebral Ischemia/Reperfusion Injury by Inhibiting Ferroptosis via SLC7A11/GPX4 Signaling.

Autor: Liu H; Department of Neurology, Yixing Traditional Chinese Medicine Hospital, Yixing, Jiangsu, 214200, China., Yue Q; Division of Nephrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.; School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China., Zhang W; Department of Neurology, Yixing Traditional Chinese Medicine Hospital, Yixing, Jiangsu, 214200, China., Ding Q; Department of Rehabilitation, Yixing Traditional Chinese Medicine Hospital, Yixing, Jiangsu, 214200, China., Yang J; Yixing Traditional Chinese Medicine Hospital, Yixing, Jiangsu, 214200, China., Lin M; Yixing Traditional Chinese Medicine Hospital, Yixing, Jiangsu, 214200, China., Sun J; Department of Neurology, Yixing Traditional Chinese Medicine Hospital, Yixing, Jiangsu, 214200, China.
Jazyk: angličtina
Zdroj: Advanced biology [Adv Biol (Weinh)] 2024 Nov; Vol. 8 (11), pp. e2400180. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1002/adbi.202400180
Abstrakt: Xinglou Chengqi decoction (XLCQD) is a Chinese formula that offers benefits in ischemic stroke. However, the underlying mechanism of the effects of XLCQD-mediated anti-ischemic stroke effects remains obscure. This study investigates the ferroptosis mechanism of XLCQD against cerebral ischemia/reperfusion (I/R) injury using rat models of middle cerebral artery occlusion/reperfusion (MCAO/R). Ferroptosis differs from traditional cell death pathways and is linked to oxidative stress-induced lipid peroxidation and glutathione (GSH) depletion, which is essential to the development of ischemic stroke. In this study, it is shown that XLCQD improves brain infarction, neurological dysfunction, and histopathological changes caused by MCAO/R exposure, and improving I/R-induced oxidative damage through inhibition of ferroptosis via (Solute Carrier Family 7 Member 11) SLC7A11/ (glutathione peroxidase 4) GPX4 pathway. Interestingly, it is found that XLCQD-mediated protection in I/R is reversed by the silence of SLC7A11. XLCQD intervention significantly promotes GSH content and suppresses Reactive Oxygen Species(ROS), iron accumulation, as well as Malondialdehyde (MDA) generation, are markedly abrogated when SLC7A11 is knockdown by SLC7A11-shRNA transfection, indicating that SLC7A11 is the main target of XLCQD to further trigger intracellular events. In conclusion, XLCQD attenuates in vivo cerebral I/R injury by reducing ferroptosis via the SLC7A11/GPX4 pathway.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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