Cichon Natalia, Grabowska Weronika, Gorniak Leslaw, Stela Maksymilian, Harmata Piotr, Ceremuga Michal, Bijak Michal
Biohazard Prevention Centre, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
Faculty of Advanced Technologies and Chemistry, Military University of Technology, 2 gen. S. Kaliskiego St., 00-908 Warsaw, Poland.
Nutrients. 2024 Dec 28;17(1):78. doi: 10.3390/nu17010078.
Flavonoids are naturally occurring polyphenolic compounds known for their extensive range of biological activities. This review focuses on the inhibitory effects of flavonoids on acetylcholinesterase (AChE) and their potential as therapeutic agents for cognitive dysfunction. AChE, a serine hydrolase that plays a crucial role in cholinergic neurotransmission, is a key target in the treatment of cognitive impairments due to its function in acetylcholine hydrolysis. Natural polyphenolic compounds, particularly flavonoids, have demonstrated significant inhibition of AChE, positioning them as promising alternatives or adjuncts in neuropharmacology. This study specifically examines flavonoids such as quercetin, apigenin, kaempferol, and naringenin, investigating their inhibitory efficacy, binding mechanisms, and additional neuroprotective properties, including their antioxidant and anti-inflammatory effects. In vitro, in vivo, and in silico analyses reveal that these flavonoids effectively interact with both the active and peripheral anionic sites of AChE, resulting in increased acetylcholine levels and the stabilization of cholinergic signaling. Their mechanisms of action extend beyond mere enzymatic inhibition, as they also exhibit antioxidant and anti-amyloidogenic properties, thereby offering a multifaceted approach to neuroprotection. Given these findings, flavonoids hold considerable therapeutic potential as modulators of AChE, with implications for enhancing cognitive function and treating neurodegenerative diseases. Future studies should prioritize the enhancement of flavonoid bioavailability, evaluate their efficacy in clinical settings, and explore their potential synergistic effects when combined with established therapies to fully harness their potential as neurotherapeutic agents.
黄酮类化合物是天然存在的多酚类化合物，以其广泛的生物活性而闻名。本综述重点关注黄酮类化合物对乙酰胆碱酯酶（AChE）的抑制作用及其作为认知功能障碍治疗药物的潜力。AChE是一种丝氨酸水解酶，在胆碱能神经传递中起关键作用，由于其在乙酰胆碱水解中的功能，它是治疗认知障碍的关键靶点。天然多酚类化合物，特别是黄酮类化合物，已显示出对AChE的显著抑制作用，使其成为神经药理学中有前景的替代物或辅助药物。本研究具体考察了槲皮素、芹菜素、山奈酚和柚皮素等黄酮类化合物，研究它们的抑制效果、结合机制以及其他神经保护特性，包括抗氧化和抗炎作用。体外、体内和计算机模拟分析表明，这些黄酮类化合物能有效地与AChE的活性位点和外周阴离子位点相互作用，从而提高乙酰胆碱水平并稳定胆碱能信号传导。它们的作用机制不仅限于单纯的酶抑制，还表现出抗氧化和抗淀粉样蛋白生成特性，从而提供了一种多方面的神经保护方法。鉴于这些发现，黄酮类化合物作为AChE调节剂具有相当大的治疗潜力，对增强认知功能和治疗神经退行性疾病具有重要意义。未来的研究应优先提高黄酮类化合物的生物利用度，评估它们在临床环境中的疗效，并探索它们与现有疗法联合使用时的潜在协同效应，以充分发挥其作为神经治疗药物的潜力。
