Myricetin attenuates hypoxic-ischemic brain damage in neonatal rats via NRF2 signaling pathway

Tingting Chen; Yingying Hu; Liying Lu; Qianlei Zhao; Xiaoyue Tao; Bingqing Ding; Shangqin Chen; Jianghu Zhu; Xiaoling Guo; Zhenlang Lin

doi:10.3389/fphar.2023.1134464

Myricetin attenuates hypoxic-ischemic brain damage in neonatal rats via NRF2 signaling pathway

Front Pharmacol. 2023 Mar 8:14:1134464. doi: 10.3389/fphar.2023.1134464. eCollection 2023.

Authors

Tingting Chen^{1

2}, Yingying Hu^{1

2}, Liying Lu^{1

2}, Qianlei Zhao^{1

2}, Xiaoyue Tao^{1

2}, Bingqing Ding^{1

2}, Shangqin Chen^{1

2}, Jianghu Zhu^{1

2}, Xiaoling Guo^{1

3

4

5}, Zhenlang Lin^{1

2

4}

Affiliations

¹ Department of Pediatrics, The Second School of Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
² Key Laboratory of Perinatal Medicine of Wenzhou, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
³ Basic Medical Research Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
⁴ Key Laboratory of Structural Malformations in Children of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
⁵ Key Laboratory of Children Genitourinary Diseases of Wenzhou, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Abstract

Introduction: Hypoxic-ischemic encephalopathy (HIE) is a crucial cause of neonatal death and neurological sequelae, but currently there is no effective therapy drug for HIE. Both oxidative stress and apoptosis play critical roles in the pathological development of HIE. Myricetin, a naturally extracted flavonol compound, exerts remarkable effects against oxidative stress, apoptosis, and inflammation. However, the role and underlying molecular mechanism of myricetin on HIE remain unclear. Methods: In this study, we established the neonatal rats hypoxic-ischemic (HI) brain damage model in vivo and CoCl₂ induced PC1₂ cell model in vitro to explore the neuroprotective effects of myricetin on HI injury, and illuminate the potential mechanism. Results: Our results showed that myricetin intervention could significantly reduce brain infarction volume, glia activation, apoptosis, and oxidative stress marker levels through activating NRF2 (Nuclear factor-E2-related factor 2) and increase the expressions of NRF2 downstream proteins NQO-1 and HO-1. In addition, the NRF2 inhibitor ML385 could significantly reverse the effects of myricetin. Conclusion: This study found that myricetin might alleviate oxidative stress and apoptosis through NRF2 signaling pathway to exert the protective role for HI injury, which suggested that myricetin might be a promising therapeutic agent for HIE.

Keywords: NRF2 signaling pathway; apoptosis; myricetin; neonatal hypoxic-ischemic (HI) brain injury; oxidative stress.

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 82271747) and Wenzhou Science and Technology Bureau Foundation (No. Y20190004).