Ran Niandong, Liu Jie, Xu Jian, Zhang Yongping, Guo Jiangtao
School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
National Engineering and Technology Research Center of Miao Medicine, Guiyang 550025, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2025 Apr 20;45(4):785-798. doi: 10.12122/j.issn.1673-4254.2025.04.14.
To investigate the active components and possible mechanisms of n-butanol fraction of Schltr. ethanol extract for treating Alzheimer's disease (AD).
The active components of n-butanol fraction of Schltr. ethanol extract were analyzed using UPLC-QE-MS technique. In a SD rat model of AD induced by treatment with AlCl and D-gal, the therapeutic effects of low, moderate and high doses of the n-butanol fraction, saline, and donepezil hydrochloride were evaluated using ELISA, HE and Nissl staining, immunohistochemistry and Western blotting. The therapeutic mechanisms of the n-butanol fraction were explored using network pharmacology and molecular docking.
Seventeen active components were identified from the n-butanol fraction of Schltr. ethanol extract, including phenylpropanoids, flavonoids, anthraquinones, triterpenoids, steroids, and volatile oils. In the rat models of AD, treatment with the n-butanol fraction significantly lowed AChE content in the hippocampus, increased the contents of ACh, SOD, CAT, and GSH-Px, enhanced the expressions of neuronal apoptotic factors Bcl-2, PI3K, Akt, p-PI3K, and p-Akt, and reduced the expressions of Bax and caspase-3 proteins. The treatment also dose-dependently up-regulated hippocampal expressions of Nrf-2, HO-1 and BDNF and down-regulated Keap-1, Aβ and Tau expressions. Bioinformatics analysis identified 14 key intersected targets (including TNF, AKT1 and ESR1) between the n-butanol fraction and AD.
The therapeutic effect of n-butanol fraction of Schltr. ethanol extract in AD mice is mediated by its multiple active components that regulate multiple targets and pathways.
研究 Schltr.乙醇提取物正丁醇部位治疗阿尔茨海默病（AD）的活性成分及可能机制。
采用超高效液相色谱-四极杆飞行时间质谱联用（UPLC-QE-MS）技术分析 Schltr.乙醇提取物正丁醇部位的活性成分。在氯化铝和 D-半乳糖诱导的 SD 大鼠 AD 模型中，采用酶联免疫吸附测定（ELISA）、苏木精-伊红（HE）染色、尼氏染色、免疫组织化学和蛋白质免疫印迹法评估低、中、高剂量正丁醇部位、生理盐水及盐酸多奈哌齐的治疗效果。运用网络药理学和分子对接技术探索正丁醇部位的治疗机制。
从 Schltr.乙醇提取物正丁醇部位鉴定出 17 种活性成分，包括苯丙素类、黄酮类、蒽醌类、三萜类、甾体类和挥发油类。在 AD 大鼠模型中，正丁醇部位治疗可显著降低海马组织中乙酰胆碱酯酶（AChE）含量，增加乙酰胆碱（ACh）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）含量，增强神经元凋亡因子 Bcl-2、磷脂酰肌醇-3-激酶（PI3K）、蛋白激酶 B（Akt）、磷酸化磷脂酰肌醇-3-激酶（p-PI3K）和磷酸化蛋白激酶 B（p-Akt）的表达，降低 Bax 和半胱天冬酶-3（caspase-3）蛋白的表达。该治疗还剂量依赖性地上调海马组织中核因子 E2 相关因子 2（Nrf-2）、血红素加氧酶-1（HO-1）和脑源性神经营养因子（BDNF）的表达，下调 Kelch 样环氧氯丙烷相关蛋白-1（Keap-1）、β淀粉样蛋白（Aβ）和 Tau 蛋白的表达。生物信息学分析确定了正丁醇部位与 AD 之间的 14 个关键交集靶点（包括肿瘤坏死因子（TNF）、蛋白激酶 B1（AKT1）和雌激素受体 1（ESR1））。
Schltr.乙醇提取物正丁醇部位对 AD 小鼠的治疗作用是由其多种活性成分介导的，这些成分可调节多个靶点和通路。
