Ahmed H Shafeeq
Bangalore Medical College and Research Institute, K.R Road, Bangalore, 560002, Karnataka, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 16. doi: 10.1007/s00210-025-04154-3.
Calycosin, a naturally occurring isoflavonoid found predominantly in Astragalus membranaceus, exhibits significant therapeutic potential in various neurological conditions. Its multifaceted bioactive properties-antioxidant, anti-inflammatory, and anti-apoptotic-position it as a promising candidate for neuroprotection and neuroregeneration. This review explores calycosin's mechanisms of action, including its modulation of key signaling pathways such as HMGB1/TLR4/NF-κB (high mobility group box 1/toll-like receptor 4/nuclear factor kappa B), phosphatidylinositol-3-kinase (PI3 K)/Akt, ERK1/2 (extracellular signal-regulated kinase 1/2), and Hsp90/Akt/p38. In cerebral ischemia/reperfusion injury, calycosin reduces oxidative stress markers like ROS (reactive oxygen species) and MDA (malondialdehyde), enhances antioxidant enzymes (SOD (superoxide dismutase) and GPX (glutathione peroxidase)), and downregulates pro-inflammatory cytokines (TNF-α, IL-1β) through the HMGB1/TLR4/NF-κB pathway. It also inhibits autophagy via the STAT3/FOXO3a pathway and apoptosis by modulating Bax and Bcl-2 expression. In neuro-oncology, calycosin inhibits glioblastoma cell migration and invasion by modulating the TGF-β-mediated mesenchymal properties and suppressing the c-Met and CXCL10 signaling pathways. Additionally, it enhances the efficacy of temozolomide in glioma treatment through apoptotic pathways involving caspase-3 and caspase-9. Calycosin shows promise in Alzheimer's disease by reducing β-amyloid production and tau hyperphosphorylation via the GSK-3β pathway and improving mitochondrial function through the peroxisome proliferator-activated receptor gamma coactivator 1-Alpha (PGC-1α)/mitochondrial transcription factor A (TFAM) signaling pathway. In Parkinson's disease, calycosin mitigates oxidative stress, prevents dopaminergic neuronal death, and reduces neuroinflammation by inhibiting the TLR/NF-κB and MAPK pathways. It has also shown therapeutic potential in meningitis and even neuroprotective effects against hyperbilirubinemia-induced nerve injury. Despite these promising findings, further research, including detailed mechanistic studies and clinical trials, is needed to fully understand calycosin's therapeutic mechanisms and validate its potential in human subjects. Developing advanced delivery systems and exploring synergistic therapeutic strategies could further enhance its clinical application and effectiveness.
毛蕊异黄酮是一种主要存在于黄芪中的天然异黄酮，在多种神经疾病中展现出显著的治疗潜力。其多方面的生物活性特性——抗氧化、抗炎和抗凋亡——使其成为神经保护和神经再生的有希望的候选物。本综述探讨了毛蕊异黄酮的作用机制，包括其对关键信号通路的调节，如HMGB1/TLR4/NF-κB（高迁移率族蛋白B1/ Toll样受体4/核因子κB）、磷脂酰肌醇-3-激酶（PI3K）/Akt、细胞外信号调节激酶1/2（ERK1/2）以及热休克蛋白90（Hsp90）/Akt/p38。在脑缺血/再灌注损伤中，毛蕊异黄酮可降低活性氧（ROS）和丙二醛（MDA）等氧化应激标志物水平，增强抗氧化酶（超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPX））活性，并通过HMGB1/TLR4/NF-κB通路下调促炎细胞因子（肿瘤坏死因子-α、白细胞介素-1β）。它还通过信号转导子和转录激活子3（STAT3）/叉头框蛋白O3a（FOXO3a）通路抑制自噬，并通过调节Bax和Bcl-2表达抑制细胞凋亡。在神经肿瘤学方面，毛蕊异黄酮通过调节转化生长因子-β（TGF-β）介导的间充质特性并抑制c-Met和CXC趋化因子配体10（CXCL10）信号通路，抑制胶质母细胞瘤细胞的迁移和侵袭。此外，它通过涉及半胱天冬酶-3和半胱天冬酶-9的凋亡途径增强替莫唑胺在胶质瘤治疗中的疗效。毛蕊异黄酮通过糖原合成酶激酶-3β（GSK-3β）通路减少β-淀粉样蛋白生成和tau蛋白过度磷酸化，并通过过氧化物酶体增殖物激活受体γ辅激活因子1α（PGC-1α）/线粒体转录因子A（TFAM）信号通路改善线粒体功能，在阿尔茨海默病中显示出前景。在帕金森病中，毛蕊异黄酮通过抑制Toll样受体（TLR）/NF-κB和丝裂原活化蛋白激酶（MAPK）通路减轻氧化应激，防止多巴胺能神经元死亡，并减轻神经炎症。它在脑膜炎中也显示出治疗潜力，甚至对高胆红素血症诱导的神经损伤具有神经保护作用。尽管有这些有前景的发现，但仍需要进一步研究，包括详细的机制研究和临床试验，以充分了解毛蕊异黄酮的治疗机制并验证其在人体中的潜力。开发先进的给药系统并探索协同治疗策略可能会进一步提高其临床应用和疗效。
