2. Academic Validation
  3. Quercetin attenuates cerebral ischemic injury by inhibiting ferroptosis via Nrf2/HO-1 signaling pathway

Quercetin attenuates cerebral ischemic injury by inhibiting ferroptosis via Nrf2/HO-1 signaling pathway

  • Eur J Pharmacol. 2023 Dec 18:963:176264. doi: 10.1016/j.ejphar.2023.176264.
Caiwang Peng 1,  Qidi Ai 2,  Fengyan Zhao 1,  Hengli Li 1,  Yang Sun 2,  Keyan Tang 1,  Yantao Yang 3,  Naihong Chen 4,  Fang Liu 5
Affiliations

Affiliations

  • 1 School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China; Center for Standardization and Functional Engineering of Traditional Chinese Medicine in Hunan Province, Changsha, 410208, China; Key Laboratory of Modern Research of TCM, Education Department of Hunan Province, Changsha, 410208, China.
  • 2 School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China; Center for Standardization and Functional Engineering of Traditional Chinese Medicine in Hunan Province, Changsha, 410208, China.
  • 3 School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China; Center for Standardization and Functional Engineering of Traditional Chinese Medicine in Hunan Province, Changsha, 410208, China. Electronic address: 003705@hnucm.edu.cn.
  • 4 School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China; Center for Standardization and Functional Engineering of Traditional Chinese Medicine in Hunan Province, Changsha, 410208, China; Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address: chennh@imm.ac.cn.
  • 5 School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China; Center for Standardization and Functional Engineering of Traditional Chinese Medicine in Hunan Province, Changsha, 410208, China; Key Laboratory of Modern Research of TCM, Education Department of Hunan Province, Changsha, 410208, China. Electronic address: liufang@hnucm.edu.cn.
PMID: 38123006 DOI: 10.1016/j.ejphar.2023.176264
Abstract

Aims: Ischemic stroke is a severe cerebrovascular disease in which neuronal death continually occurs through multiple forms, including Apoptosis, Autophagy, Pyroptosis and Ferroptosis. Quercetin (QRC), as a natural flavonoid compound, has been reported to have pharmacological effects on ischemic injury accompanied by unclear anti-ferroptotic mechanisms. This study is designed to investigate the therapeutic effects of QRC against Ferroptosis in ischemic stroke.

Materials and methods: In vivo, the model of MCAO rats were used to assess the protective effect of QRC on cerebral ischemic. Additionally, we constructed oxidative stressed and ferroptotic cell models to explore the effects and mechanisms of QRC on Ferroptosis. The related proteins were analysed by western blotting, immunohistochemical and immunofluorescence techniques.

Results: The experiments demonstrated that QRC improves neurological deficits, infarct volume, and pathological features in MCAO rats, also increased the viability of HT-22 cells exposed to H2O2 and erastin. These results, including MDA, SOD, GSH, ROS levels and iron accumulation, indicated that QRC suppresses the generation of lipid peroxides and may involve in the regulatory of Ferroptosis. Both in vitro and in vivo, QRC was found to inhibit Ferroptosis by up-regulating GPX4 and FTH1, as well as down-regulating ACSL4. Furthermore, we observed that QRC enhances the nuclear translocation of Nrf2 and activates the downstream antioxidative proteins. Importantly, the effect of QRC on Ferroptosis can be reversed by the Nrf2 inhibitor ML385.

Conclusions: This study provides evidence that QRC has a neuroprotective effect by inhibiting Ferroptosis, demonstrating the therapeutic potential for cerebral ischemic stroke.

Keywords

Cerebral ischaemia; Ferroptosis; Nrf2/HO-1 signalling pathway; Quercetin.

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