Collaborative Innovation Center of Sichuan for Elderly Care and Health, Chengdu Medical College, Chengdu, 610500, Sichuan, China.
Department of Public Health, Chengdu Medical College, Chengdu, 610500, Sichuan, China.
Neurochem Res. 2020 May;45(5):1130-1141. doi: 10.1007/s11064-020-02992-6. Epub 2020 Feb 21.
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, and no effective therapies have been found to prevent or cure AD to date. Berberine and curcumin are extracts from traditional Chinese herbs that have a long history of clinical benefits for AD. Here, using a transgenic AD mouse model, we found that the combined berberine and curcumin treatment had a much better effect on improving the cognitive function of mice than the single-drug treatment, suggesting synergic effects of the combined berberine and curcumin treatment. In addition, we found that the combined berberine and curcumin treatment had significant synergic effects on reducing soluble amyloid-β-peptide production. Furthermore, the combination treatment also had remarkable synergic effects on decreasing inflammatory responses and oxidative stress in both the cortex and hippocampus of AD mice. We also found that the combination treatment performed much better than the single drugs in reducing the APP and BACE1 levels and increasing AMPKα phosphorylation and cell autophagy, which might be the underlying mechanism of the synergic effects. Taken together, the result of this study reveal the synergic effects and potential underlying mechanisms of the combined berberine and curcumin treatment in improving the symptoms of AD in mice. This study sheds light on a new strategy for exploring new phytotherapies for AD and also emphasizes that more research should focus on the synergic effects of herbal drugs in the future.
阿尔茨海默病(AD)是最常见的神经退行性疾病之一,迄今为止,尚未发现有效的疗法可以预防或治愈 AD。小檗碱和姜黄素是从传统中药中提取的物质,在治疗 AD 方面具有悠久的临床获益历史。在这里,我们使用转基因 AD 小鼠模型发现,小檗碱和姜黄素联合治疗在改善小鼠认知功能方面的效果明显优于单一药物治疗,提示小檗碱和姜黄素联合治疗具有协同作用。此外,我们发现小檗碱和姜黄素联合治疗在减少可溶性淀粉样β-肽产生方面具有显著的协同作用。此外,联合治疗还对 AD 小鼠皮质和海马中的炎症反应和氧化应激具有显著的协同作用。我们还发现,与单一药物相比,联合治疗在降低 APP 和 BACE1 水平、增加 AMPKα 磷酸化和细胞自噬方面表现出更好的效果,这可能是协同作用的潜在机制。综上所述,这项研究揭示了小檗碱和姜黄素联合治疗在改善 AD 小鼠症状方面的协同作用和潜在机制。该研究为探索 AD 的新植物疗法提供了新策略,同时也强调未来应更多地关注草药药物的协同作用。