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Regression of oxidative stress by targeting Nrf2/HO-1 signaling: The potential therapeutic drugs for cerebral ischemia-reperfusion injury

Hao-Ming Zhou, Yun Chai, Xi Mao, Jia-Xing Rao, Shuo Zhang, Guisheng Zhou, Kim Fey Leu, Yuping Tang, Jin‐Ao Duan

2025Biomedicine & Pharmacotherapy5 citationsDOIOpen Access PDF

Abstract

Ischemic stroke is an acute vascular event caused by occlusion of a cerebral or carotid artery, resulting in limitation of cerebral blood flow and oxygen supply. After the restoration of blood flow, oxidative stress is aggravated, resulting in the generation of free radicals exceeding the antioxidant defense capacity of the body. This imbalance is an important factor in the occurrence and development of cerebral ischemia-reperfusion injury (CIRI). It constitutes a serious risk to the health and quality of life among the elderly. Activation of the nuclear factor erythrocyte 2-associated factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway can enhance the body's ability to resist oxidative stress, which is expected to reduce CIRI. This review comprehensively examines the function and activation mechanisms of the Nrf2/HO-1 signaling pathway, specifically investigates the therapeutic potential of natural products in managing CIRI, and evaluates the safety profiles of various bioactive compounds. Furthermore, it addresses prospective advancements in this field and proposes promising directions for future research and clinical application.

Topics & Concepts

Oxidative stressMedicinePharmacologyCerebral blood flowStroke (engine)AntioxidantRisk factorIschemiaBioinformaticsMechanism (biology)Oxidative phosphorylationCarotid arteriesSignal transductionFunction (biology)AnesthesiaClinical trialOcclusionReactive oxygen speciesQuality of life (healthcare)NeuroscienceProspective cohort studyIntensive care medicineGenomics, phytochemicals, and oxidative stressHeme Oxygenase-1 and Carbon MonoxideNeuroinflammation and Neurodegeneration Mechanisms
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