Singh Alka Ashok, Katiyar Shweta, Song Minseok
Department of Life Sciences, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Department of Botany, SBN Government PG College, Barwani 451551, MP, India.
Brain Sci. 2025 Feb 27;15(3):252. doi: 10.3390/brainsci15030252.
Neurological disorders are defined by a deterioration or disruption of the nervous system's structure and function. These diseases, which include multiple sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, and schizophrenia, are caused by intricate pathological processes that include excitotoxicity, neuroinflammation, oxidative stress, genetic mutations, and compromised neurotrophic signaling. Although current pharmaceutical treatments relieve symptoms, their long-term efficacy is limited due to adverse side effects and weak neuroprotective properties. However, when combined with other neuroprotective drugs or adjunct therapy, they may offer additional benefits and improve treatment outcomes. Phytochemicals have emerged as attractive therapeutic agents due to their ability to regulate essential neurotrophic pathways, especially the brain-derived neurotrophic factor (BDNF) signaling cascade. BDNF is an important target for neurodegenerative disease (ND) treatment since it regulates neuronal survival, synaptic plasticity, neurogenesis, and neuroprotection. This review emphasizes the molecular pathways through which various phytochemicals-such as flavonoids, terpenoids, alkaloids, and phenolic compounds-stimulate BDNF expression and modulate its downstream signaling pathways, including GSK-3β, MAPK/ERK, PI3K/Akt/mTOR, CREB, and Wnt/β-catenin. This paper also highlights how phytochemical combinations may interact to enhance BDNF activity, offering new therapeutic options for ND treatment. Despite their potential for neuroprotection, phytochemicals face challenges related to pharmacokinetics, blood-brain barrier (BBB) permeability, and absorption, highlighting the need for further research into combination therapies and improved formulations. Clinical assessment and mechanistic understanding of BDNF-targeted phytotherapy should be the main goals of future studies. The therapeutic efficacy of natural compounds in regulating neurotrophic signaling is highlighted in this review, providing a viable approach to the prevention and treatment of NDs.
神经系统疾病是由神经系统结构和功能的恶化或破坏所定义的。这些疾病包括多发性硬化症、阿尔茨海默病、帕金森病、亨廷顿病和精神分裂症，是由复杂的病理过程引起的，这些过程包括兴奋性毒性、神经炎症、氧化应激、基因突变和神经营养信号受损。尽管目前的药物治疗可以缓解症状，但由于副作用和较弱的神经保护特性，它们的长期疗效有限。然而，当与其他神经保护药物或辅助治疗联合使用时，它们可能会带来额外的益处并改善治疗效果。植物化学物质因其能够调节重要的神经营养途径，特别是脑源性神经营养因子（BDNF）信号级联反应，而成为有吸引力的治疗剂。BDNF是神经退行性疾病（ND）治疗的一个重要靶点，因为它调节神经元存活、突触可塑性、神经发生和神经保护。这篇综述强调了各种植物化学物质，如黄酮类化合物、萜类化合物、生物碱和酚类化合物，通过哪些分子途径刺激BDNF表达并调节其下游信号通路，包括GSK-3β、MAPK/ERK、PI3K/Akt/mTOR、CREB和Wnt/β-连环蛋白。本文还强调了植物化学物质组合可能如何相互作用以增强BDNF活性，为ND治疗提供新的治疗选择。尽管植物化学物质具有神经保护潜力，但它们面临着与药代动力学、血脑屏障（BBB）通透性和吸收相关的挑战，这突出了对联合治疗和改进制剂进行进一步研究的必要性。对以BDNF为靶点的植物疗法的临床评估和机制理解应是未来研究的主要目标。本综述强调了天然化合物在调节神经营养信号方面的治疗效果，为ND的预防和治疗提供了一种可行的方法。
