Decoding natural products for neuroprotection: Pathway networks and structural insights for drug development
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摘要:
神经退行性疾病（NDs）——包括阿尔茨海默病、帕金森病、亨廷顿病及肌萎缩侧索硬化——是以神经元功能障碍和死亡为特征的进行性疾病，其病理机制涉及氧化应激、线粒体功能障碍、神经炎症、细胞凋亡和蛋白质错误折叠等。尽管科学研究不断进展，当前治疗方法仍主要局限于对症治疗，这凸显了对多靶点治疗策略的迫切需求。本文通过系统梳理临床前与临床研究证据，探讨天然产物的神经保护潜力，重点关注其调控神经退行性疾病关键分子通路的能力。在Scopus、ScienceDirect、PubMed、MDPI和Web of Science数据库进行文献检索，筛选出相关研究。姜黄素、白藜芦醇、人参皂苷、槲皮素等生物活性成分，以及岩藻黄素、褐藻多酚等海洋来源分子，通过调控PI3K/Akt、NF-κB、Nrf2/ARE等信号通路，展现出抗氧化、抗炎、抗淀粉样蛋白形成和线粒体保护作用，从而减轻神经元损伤并促进细胞存活。源自蜂蜜、人参、海洋大型藻类和蓝藻的天然产物表现出广谱神经保护特性，而纳米制剂技术的进步有效改善了其生物利用度与脑部渗透性。此外，基因-药物相互作用研究和基于骨架的药物设计等新兴方法，为推进临床转化开辟了新途径。尽管天然产物为对抗神经退行性疾病提供了整体性、多靶点的治疗策略，但其生物利用度与临床转化难题依然存在，未来研究需整合先进药物递送系统、精准医疗和结构修饰技术，以开发创新有效的治疗范式。
Abstract:
Neurodegenerative diseases (NDs), including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, are progressive disorders marked by neuronal dysfunction and death, driven by pathological mechanisms such as oxidative stress, mitochondrial dysfunction, neuroinflammation, apoptosis, and protein misfolding. Despite scientific advances, current treatments remain largely palliative, underscoring the need for multitargeted therapeutic strategies. This narrative review synthesizes preclinical and clinical evidence to explore the neuroprotective potential of natural products, with a focus on their ability to modulate key molecular pathways implicated in NDs. A comprehensive literature search across Scopus, ScienceDirect, PubMed, MDPI, and Web of Science identified relevant studies. Bioactive compounds such as curcumin, resveratrol, ginsenosides, quercetin, and marine-derived molecules like fucoxanthin and phlorotannin demonstrated antioxidant, anti-inflammatory, anti-amyloidogenic, and mitochondrial-protective effects by modulating pathways including PI3K/Akt, NF-κB, and Nrf2/ARE, thereby mitigating neuronal damage and promoting cell survival. Natural products from diverse sources, including honey, ginseng, marine macroalgae, and cyanobacteria, exhibited broad-spectrum neuroprotective properties, with advances in nano-formulations improving bioavailability and brain penetration. Furthermore, emerging approaches such as gene-drug interaction studies and scaffold-based drug design offer promising avenues for enhancing clinical translation. While natural products provide a holistic, multitargeted approach to combat NDs, challenges related to bioavailability and therapeutic translation persist, necessitating future research that integrates advanced drug delivery systems, precision medicine, and synthetic modifications to develop innovative and effective treatment paradigms.
关键词:
姜黄素;岩藻黄素;人参皂苷;天然产物;神经退行性疾病;褐藻多酚;槲皮素;白藜芦醇
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The authors acknowledge the support from the authority of Bengal College of Pharmaceutical Technology, Dubrajpur, West Bengal; India, Bengal College of Pharmaceutical Sciences & Research, Durgapur, West Bengal; Dr. B. C. Roy College of Pharmacy & Allied Health Sciences, Durgapur, West Bengal, Gupta College of Technological Sciences, Asansol, West Bengal; Guru Nanak Institute of Pharmaceutical Science and Technology, Kolkata, West Bengal; and P. G. Institute Of Medical Sciences, Chandrakona, West Bengal; for completing the manuscript.
