朱燃, 黄田喜, 赵雪梅, 张冀民, 梁平. 10种中草药成分对体外过表达Aβ的影响及机制探讨J. 药学学报, 2014,49(6): 800-806.
引用本文: 朱燃, 黄田喜, 赵雪梅, 张冀民, 梁平. 10种中草药成分对体外过表达Aβ的影响及机制探讨J. 药学学报, 2014,49(6): 800-806.
ZHU Ran, HUANG Tian-xi, ZHAO Xue-mei, ZHANG Ji-min, LIANG Ping. Screening of 10 types of Chinese herbal compounds inhibiting Aβ and their possible related mechanism in vitroJ. Acta Pharmaceutica Sinica, 2014,49(6): 800-806.
Citation: ZHU Ran, HUANG Tian-xi, ZHAO Xue-mei, ZHANG Ji-min, LIANG Ping. Screening of 10 types of Chinese herbal compounds inhibiting Aβ and their possible related mechanism in vitroJ. Acta Pharmaceutica Sinica, 2014,49(6): 800-806.

10种中草药成分对体外过表达Aβ的影响及机制探讨

Screening of 10 types of Chinese herbal compounds inhibiting Aβ and their possible related mechanism in vitro

  • 摘要: 筛选对阿尔茨海默病(Alzheimer's disease,AD)患者脑内老年斑的组成成分β-淀粉样蛋白(β-amyloid peptide,Aβ)有抑制作用的中草药成分,并探讨其可能机制。从资料中选出10种具有潜在治疗AD的中草药成分,分别以不同药物浓度(0.5~100 µmol·L-1)作用于两种双基因转染细胞模型(117细胞模型: 过表达Aββ-分泌酶;146细胞模型: 过表达Aβγ-分泌酶),一定时间后,用ELISA法测定各组细胞外Aβ水平,初筛出具有降低细胞外Aβ的中草药成分,并估算其最佳药物浓度范围,然后分别观察其对细胞形态、活力及凋亡率的影响,并分析其对模型细胞内Aβ水平、βγ-分泌酶活性的作用效果。初筛结果显示,10种中草药成分中有4种能浓度依赖性降低两种模型外Aβ水平,分别为隐丹参酮、黄芪总皂苷、天麻素和芍药苷,其浓度分别在0.5~5.0、0.5~5.0、5.0~50和1.0~25 µmol·L-1内时效果最为显著。进一步的研究表明,这4种中草药成分对细胞活性无抑制作用,对细胞内Aβ的降低水平大于细胞外,黄芪总皂苷和天麻素还分别对β-分泌酶、γ-分泌酶活性有浓度依赖性抑制作用;其中,黄芪总皂苷对β-分泌酶活性的最高抑制率达78.2%,天麻素对γ-分泌酶活性的最高抑制率达80.3%。综上所述,隐丹参酮、黄芪总皂苷、天麻素和芍药苷对细胞模型产生的Aβ均有浓度依赖性抑制作用,其中黄芪总皂苷、天麻素抑制Aβ的作用机制可能分别与抑制β-分泌酶活性、γ-分泌酶活性有关。

     

    Abstract: This study is to screen the Chinese herbal compounds which could inhibit the production of Aβ and investigate the underlying mechanism.Ten types of compounds which have potential value in the treatment of AD were selected as initial screening trial.The cell models which used could overexpress Aβ and β-secretases or Aβ and γ-secretases.Extracellular Aβ was determined by ELISA after the cell models treated with different concentrations of compounds (0.5-100 µmol·L-1), separately.Then the compounds were selected which could inhibit extracellular Aβ and their best concentration ranges were decided, too.Furthermore, the cell viability and apoptosis rate, the level of intracellular Aβ, β and γ-secretases were determined after the cell models treated with different concentrations of selected compounds.The results showed that 4 of the 10 compounds could reduce the level of extracellular Aβ; they were cryptotanshinone, astragalosides, gastrodin and paeoniflorin, and their best concentration ranges were 0.5-5.0, 0.5-5.0, 5.0-50, 1.0-25 µmol·L-1, respectively.Further study indicated that the 4 selected compounds were nontoxic to the cellular models and lowering intracellular Aβwere more effective compared with extracellular; of which astragalosides and gastrodin showed dose-dependent inhibition to the activities of β and γ-secretases, with the maximum inhibiting rates of 78.2% and 80.3%,respectively.In conclusion, cryptotanshinone, astragalosides, gastrodin and paeoniflorin could inhibit theexpression and secretion of Aβ, and the underlying inhibiting mechanism of astragalosides and gastrodin were related with the reduction of the β and γ-secretase activities, respectively.

     

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