Kopalli Spandana Rajendra, Behl Tapan, Kyada Ashishkumar, Rekha M M, Kundlas Mayank, Rani Pooja, Nathiya Deepak, Satyam Naidu K, Gulati Monica, Bhise Manish, Gupta Priyanka, Wal Pranay, Fareed Mohammad, Ramniwas Seema, Koppula Sushruta, Gasmi Amin
Department of Bioscience and Biotechnology, Sejong University, Gwangjin-gu, Seoul 05006 Republic of Korea.
Amity School of Pharmaceutical Sciences, Amity University, Punjab 140306, India.
Neuroscience. 2025 Mar 17;569:161-183. doi: 10.1016/j.neuroscience.2025.02.007. Epub 2025 Feb 6.
Flavonoids are a broad family of polyphenolic chemicals that are present in a wide variety of fruits, vegetables, and medicinal plants. Because of their neuroprotective qualities, flavonoids have attracted a lot of interest. The potential of flavonoids to control synaptic plasticity-a crucial process underlying memory, learning, and cognitive function-is becoming more and more clear. Dysregulation of synaptic plasticity is a feature of neurodegenerative diseases such as amyotrophic lateral sclerosis (0.4 %), Parkinson's (1-2 %), Alzheimer's (5-7 %), and Huntington's ((0.2 %)). This review discusses the molecular mechanisms via which flavonoids influence synaptic plasticity as well as their therapeutic potential in neurodegenerative diseases. Flavonoids modulate key signaling pathways such as MAPK/ERK and PI3K/Akt/mTOR to support neuroprotection, synaptic plasticity, and neuronal health, while also influencing neurotrophic factors (BDNF, NGF) and their receptors (TrkB, TrkA). They regulate neurotransmitter receptors like GABA, AMPA, and NMDA to balance excitatory and inhibitory transmission, and exert antioxidant effects via the Nrf2-ARE pathway and anti-inflammatory actions by inhibiting NF-κB signaling, highlighting their potential for treating neurodegenerative diseases. These varied reactions support the preservation of synapse function and neuronal integrity in the face of neurodegenerative insults. Flavonoids can reduce the symptoms of neurodegeneration, prevent synaptic loss, and enhance cognitive function, according to experimental studies. However, there are still obstacles to using these findings in clinical settings, such as limited bioavailability and the need for consistent dose. The focus of future research should be on improving flavonoid delivery systems and combining them with conventional medications.
黄酮类化合物是一大类多酚化学物质，广泛存在于各种水果、蔬菜和药用植物中。由于其神经保护特性，黄酮类化合物引起了广泛关注。黄酮类化合物调控突触可塑性（这是记忆、学习和认知功能的关键过程）的潜力越来越明显。突触可塑性失调是肌萎缩侧索硬化症（0.4%）、帕金森病（1%-2%）、阿尔茨海默病（5%-7%）和亨廷顿病（0.2%）等神经退行性疾病的一个特征。本文综述了黄酮类化合物影响突触可塑性的分子机制及其在神经退行性疾病中的治疗潜力。黄酮类化合物调节关键信号通路，如MAPK/ERK和PI3K/Akt/mTOR，以支持神经保护、突触可塑性和神经元健康，同时还影响神经营养因子（BDNF、NGF）及其受体（TrkB、TrkA）。它们调节GABA、AMPA和NMDA等神经递质受体，以平衡兴奋性和抑制性传递，并通过Nrf2-ARE途径发挥抗氧化作用，通过抑制NF-κB信号发挥抗炎作用，突出了它们治疗神经退行性疾病的潜力。这些不同的反应有助于在面对神经退行性损伤时维持突触功能和神经元完整性。实验研究表明，黄酮类化合物可以减轻神经退行性症状，防止突触丧失，并增强认知功能。然而，在临床环境中应用这些发现仍存在障碍，如生物利用度有限和需要一致的剂量。未来研究的重点应是改进黄酮类化合物的递送系统，并将其与传统药物联合使用。
