返回 
加入收藏
鬼针草总黄酮对阿尔茨海默病的改善作用及机制
x
请在关注微信后，向客服人员索取文件
| 篇名： | 鬼针草总黄酮对阿尔茨海默病的改善作用及机制 |
| TITLE： | Improvement effects and mechanism of total flavonoids from Bidens pilosa on Alzheimer’s disease |
| 摘要： | 目的 探讨鬼针草总黄酮（TFB）对阿尔茨海默病（AD）的改善作用及潜在机制。方法采用网络药理学方法，挖掘TFB用于AD的活性成分及核心靶点，进行基因本体（GO）、京都基因和基因组数据库（KEGG）富集分析。基于网络药理学结果，以雄性BALB/c小鼠为对象，以D-半乳糖皮下注射+氯化铝灌胃构建AD模型，考察TFB对AD小鼠行为学指标（逃避潜伏期、穿越平台次数、原平台象限停留时间占比）、乙酰胆碱酯酶（AChE）、乙酰胆碱（ACh）、胆碱乙酰转移酶（ChAT）、β淀粉样蛋白（Aβ）、磷酸化Tau蛋白（p-Tau）及炎症因子[白细胞介素1β（IL-1β）、IL-6、肿瘤坏死因子α（TNF-α）]、海马区神经元病理学变化、相关蛋白及mRNA表达的影响。结果共筛选得TFB活性成分6种（木犀草素、槲皮素、山柰酚等），TFB与AD的共同靶点165个，核心靶点29个（Akt1、TP53等）；共同靶点主要富集于基因表达的正调控、细胞凋亡过程的负调控等生物过程，酶结合、相同蛋白结合等分子功能，细胞外间隙、质膜、受体复合物等细胞组分，以及癌症通路、磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）信号通路等。动物实验结果显示，与模型组比较，各药物组小鼠海马CA3区神经元排列紊乱、变性坏死等病理改变均有所缓解，其逃避潜伏期（TFB低剂量组除外），脑组织中AChE（TFB低剂量组除外）、Aβ40、Aβ42（TFB低剂量组除外）、p-Tau（TFB低、中剂量组除外）、IL-1β、IL-6（TFB低剂量组除外）、TNF-α含量，以及Bax、caspase-3mRNA的表达均显著缩短/降低/下调，穿越平台次数，原平台象限停留时间占比，ChAT和ACh含量，PI3K、Akt蛋白的磷酸化水平和PI3K、Akt、Bcl-2mRNA（TFB低、中剂量组PI3K、AktmRNA，TFB低剂量组Bcl-2mRNA除外）的表达均显著升高（P＜0.05或P＜0.01）。结论TFB可通过多成分、多靶点、多通路发挥抗AD作用，其机制可能与激活PI3K/Akt信号通路、改善胆碱能系统、减少Aβ沉积和Tau蛋白过度磷酸化、抑制神经炎症反应和神经元细胞凋亡有关。 |
| ABSTRACT： | OBJECTIVE To investigate the improvement effects of total flavonoids from Bidens pilosa （TFB）against Alzheimer’s disease （AD） and elucidate its potential mechanism. METHODS The network pharmacology was adopted to explore active constituents and core targets of TFB for AD， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Based on the results of network pharmacology， an AD model was induced in male BALB/c mice by D-galactose subcutaneous injection and aluminum chloride gavage. The effects of TFB on behavioral indicators （including escape latency， the number of platform crossings， and the proportion of dwell time spent in the original platform quadrant）， as well as on acetylcholinesterase （AChE）， acetylcholine （ACh）， choline acetyltransferase （ChAT）， amyloid β-protein （Aβ）， phosphorylated Tau protein （p-Tau）， and inflammatory factors [interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α）] were investigated. Additionally， its effects on the pathological changes in hippocampal neurons， as well as the expressions of related proteins and mRNAs were evaluated. RESULTS Network pharmacology revealed 6 active components in TFB （e.g. luteolin， quercetin， kaempferol） and 165 overlapping targets with AD， including 29 core targets （Akt1， TP53， etc.）. The common targets were primarily enriched in biological processes such as positive regulation of gene expression and negative regulation of apoptotic processes， molecular functions including enzyme binding and identical protein binding， cellular components like extracellular space， plasma membrane and receptor complex， as well as signaling pathways such as cancer pathways and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. The results of animal experiments showed that， compared with model group， the pathological changes such as disordered arrangement， degeneration， and necrosis of neurons in the hippocampal CA3 region of mice in administration groups were alleviated. The escape latency （except for the low-dose TFB group）， the contents of AChE （except for the low-dose TFB group）， Aβ40， Aβ42 （except for the low-dose TFB group）， p-Tau （except for the low- and medium-dose TFB groups）， IL-1β， IL-6 （except for the low-dose TFB group）， and TNF- α in brain tissue， as well as the expressions of Bax and caspase-3 mRNA， were all significantly shortened/reduced/down-regulated. Conversely， the number of platform crossings， the proportion of dwell time spent in the original platform quadrant， the contents of ChAT and ACh， the phosphorylation levels of PI3K and Akt， and the mRNA expressions of PI3K， Akt and Bcl-2 （except for PI3K mRNA and Akt mRNA in the low- and medium-dose TFB groups， and Bcl-2 mRNA in the low-dose TFB group） were all significantly increased （P＜0.05 or P＜0.01）. CONCLUSIONS TFB can exert anti-AD effect through multiple components， multiple targets， and multiple pathways. Its underlying mechanisms may be related to the activation of the PI3K/Akt signaling pathway， improvement of the cholinergic system， reduction of Aβ deposition and Tau protein hyperphosphorylation， as well as inhibition of neuroinflammatory responses and neuronal apoptosis. |
| 期刊： | 2025年第36卷第24期 |
| 作者： | 庞晓军；唐丰曼；李倩倩 |
| AUTHORS： | PANG Xiaojun，TANG Fengman，LI Qianqian |
| 关键字： | 鬼针草总黄酮；阿尔茨海默病；PI3K/Akt信号通路；网络药理学 |
| KEYWORDS： | total flavonoids of Bidens pilosa； Alzheimer’s disease； PI3K/Akt signaling pathway； network pharmacology |
| 阅读数： | 0 次 |
| 本月下载数： | 0 次 |
* 注：未经本站明确许可，任何网站不得非法盗链资源下载连接及抄袭本站原创内容资源!在此感谢您的支持与合作！
