Ecdysterone improves oxidative damage induced by acute ischemic stroke via inhibiting ferroptosis in neurons through ACSL4

Jia Sun; Keke Zhao; Wenyue Zhang; Chen Guo; Hua Liu

doi:10.1016/j.jep.2024.118204

Ecdysterone improves oxidative damage induced by acute ischemic stroke via inhibiting ferroptosis in neurons through ACSL4

J Ethnopharmacol. 2024 Apr 26:331:118204. doi: 10.1016/j.jep.2024.118204. Online ahead of print.

Authors

Jia Sun¹, Keke Zhao², Wenyue Zhang¹, Chen Guo³, Hua Liu⁴

Affiliations

¹ Department of Encephalopathy, Yixing Traditional Chinese Medicine Hospital, Yixing, 214200, China.
² College of Pharmacy, Ningxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, Ningxia, 750004, China.
³ Department of Brain Surgery, Yixing Traditional Chinese Medicine Hospital, Yixing, 214200, China.
⁴ Department of Encephalopathy, Yixing Traditional Chinese Medicine Hospital, Yixing, 214200, China. Electronic address: jxlh1983@outlook.com.

PMID: 38679397
DOI: 10.1016/j.jep.2024.118204

Abstract

Ethnopharmacological relevance: Acute ischemic stroke (AIS) is a prominent cause of disability and mortality around the world. Achyranthes bidentata Blume, a regularly prescribed traditional Chinese herb, plays a significant role in traditional Chinese stroke therapy due to its ability to promote blood circulation and remove stasis. Ecdysterone (EDS) is one of the key active components in Achyranthes bidentata Blume, which exhibits antioxidant and anti-cerebral hypoxia properties. However, whether EDS improves AIS and the mechanism of action of AIS is still unclear.

Aim of the study: The objective of this study was to observe whether EDS ameliorates oxidative damage caused by AIS by inhibiting ferroptosis in neurons via ACSL4.

Materials and methods: In vivo, the Middle cerebral artery occlusion (MCAO) rat model was established for research. After treatment with EDS, Neurologic score, TTC, HE and FJC staining were performed, followed by measurements of oxidative stress-related indicators, the content of Fe²⁺, iron deposition levels and expression of ACSL4, NCOA4 and FTH1 in brain tissue. In vitro, oxygen-glucose deprivation and reperfusion (OGD/R) cell model was established. After treatment with EDS, cell viability, oxidative stress-related indicators, the content of Fe²⁺ and expression of ACSL4, NCOA4 and FTH1 were detected. In addition, the overexpression of ACSL4 and CETSA technology further elucidated that EDS improves AIS through ACSL4.

Results: The results showed that the treatment of EDS could improve the oxidative damage of MCAO rats by inhibiting ferroptosis, and then improve AIS. Importantly, EDS inhibited ferroptosis via ACSL4, thereby inhibiting oxidative stress in MCAO rats or OGD/R-induced PC12 cells.

Conclusions: These results provide evidence that EDS ameliorates oxidative damage caused by AIS by inhibiting ferroptosis via ACSL4, and provide new insights into the potential use of EDS as an effective drug development candidate for AIS.

Keywords: ACSL4; Acute ischemic stroke; Ecdysterone; Ferroptosis; Oxidative stress.