Yoo Ki-Yeon, Won Moo-Ho, Ahn Ji Hyeon, Park Joon Ha
Department of Anatomy, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea.
Research Institute for Dental Engineering, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea.
Biology (Basel). 2025 Sep 1;14(9):1153. doi: 10.3390/biology14091153.
Brain ischemia-reperfusion (I/R) injury, commonly occurring in ischemic stroke and post-cardiac arrest scenarios, results in complex secondary damage involving oxidative stress, inflammation, apoptosis, and blood-brain barrier (BBB) breakdown. Despite decades of research, no pharmacological agent has yet been clinically approved for post-I/R neuroprotection. Natural compounds have recently gained attention for their multimodal therapeutic potential, including antioxidant, anti-inflammatory, anti-apoptotic, and neuroregenerative effects. This review highlights nine promising candidates-resveratrol, curcumin, quercetin, berberine, ginkgolide B, baicalin, naringin, fucoidan, and astaxanthin-that exhibit efficacy in experimental models of I/R injury when administered after the insult. Their chemical structures, pharmacokinetics, and mechanisms of action are described in detail, focusing on key signaling pathways such as nuclear factor erythroid 2-related (Nrf2), nuclear factor kappa B (NF-B), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and brain-derived neurotrophic factor (BDNF). Importantly, we outline the selection criteria for these compounds, including demonstrated neuroprotective efficacy, mechanistic clarity, and translational feasibility. While several challenges remain-such as limited bioavailability, BBB penetration, and species-specific metabolism-emerging strategies like nanoparticle delivery, synthetic analogs, and drug combinations offer potential solutions. By emphasizing the therapeutic versatility and mechanistic diversity of these natural agents, this review supports their clinical potential and encourages further preclinical optimization and biomarker-guided human trials.
脑缺血再灌注（I/R）损伤常见于缺血性中风和心脏骤停后，会导致包括氧化应激、炎症、细胞凋亡和血脑屏障（BBB）破坏在内的复杂继发性损伤。尽管经过了数十年的研究，但尚无药物被临床批准用于I/R后的神经保护。天然化合物因其多模式治疗潜力，包括抗氧化、抗炎、抗凋亡和神经再生作用，最近受到了关注。本综述重点介绍了九种有前景的化合物——白藜芦醇、姜黄素、槲皮素、黄连素、银杏内酯B、黄芩苷、柚皮苷、岩藻依聚糖和虾青素——它们在损伤后给药时，在I/R损伤的实验模型中显示出疗效。详细描述了它们的化学结构、药代动力学和作用机制，重点关注关键信号通路，如核因子红细胞2相关因子（Nrf2）、核因子κB（NF-κB）、磷脂酰肌醇3激酶/蛋白激酶B（PI3K/Akt）和脑源性神经营养因子（BDNF）。重要的是，我们概述了这些化合物的选择标准，包括已证实的神经保护疗效、作用机制的清晰度和转化可行性。虽然仍存在一些挑战，如生物利用度有限、BBB穿透性和物种特异性代谢，但纳米颗粒递送、合成类似物和药物组合等新兴策略提供了潜在的解决方案。通过强调这些天然药物的治疗多功能性和作用机制多样性，本综述支持它们的临床潜力，并鼓励进一步的临床前优化和生物标志物指导的人体试验。
