Network Pharmacology Analysis and Molecular Characterization of the Herbal Medicine Formulation Qi-Fu-Yin for the Inhibition of the Neuroinflammatory Biomarker iNOS in Microglial BV-2 Cells: Implication for the Treatment of Alzheimer’s Disease
Network Pharmacology Analysis and Molecular Characterization of the Herbal Medicine Formulation Qi-Fu-Yin for the Inhibition of the Neuroinflammatory Biomarker iNOS in Microglial BV-2 Cells: Implication for the Treatment of Alzheimer’s Disease
复制标题
中草药制剂芪附饮抑制小胶质细胞 BV-2 细胞中神经炎症生物标志物 iNOS 的网络药理学分析和分子表征：对治疗阿尔茨海默病的启示
DOI：
10.1155/2020/5780703
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发表时间：
2020
影响因子：
--
通讯作者：
Jianhui Rong
中科院分区：
文献类型：
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作者：
Fung Yin Ngo;Weiwei Wang;Qilei Chen;Jia Zhao;Hubiao Chen;Jin-Ming Gao;Jianhui Rong
异常的小胶质细胞激活驱动阿尔茨海默病（AD）中的神经炎症和神经变性。本研究旨在研究中药方剂芪附饮（QFY）是否可以抑制培养的BV-2小胶质细胞的炎症活化。采用网络药理学方法预测QFY的活性化合物、蛋白质靶点和受影响的途径。通过基因本体论（GO）和途径富集分析了靶点的代表性途径和分子功能。从七种中药成分中筛选出145个有效成分。目标（例如，基于与AD和炎症的相关性，预测所选活性化合物的MAPT、APP、ACHE、iNOS和考克斯-2）。作为验证，通过水提取、乙醇沉淀和HPLC分离依次制备级分，并通过蛋白质印迹技术测定脂多糖-（LPS-）攻击的BV-2细胞中两种关键促炎生物标志物iNOS和考克斯-2的下调。此外，QFY在90%乙醇中的化合物下调BV-2细胞中的iNOS，但对考克斯-2诱导无活性。清肠方中，黄芪和人参对iNOS的诱导有选择性抑制作用。此外，化学分析确定了人参皂苷，特别是Rg 3，作为抗神经炎性化合物。清瘟口服液可能通过下调小胶质细胞中的iNOS而减轻神经炎症。
Aberrant microglial activation drives neuroinflammation and neurodegeneration in Alzheimer’s disease (AD). The present study is aimed at investigating whether the herbal formula Qi‐Fu‐Yin (QFY) could inhibit the inflammatory activation of cultured BV‐2 microglia. A network pharmacology approach was employed to predict the active compounds of QFY, protein targets, and affected pathways. The representative pathways and molecular functions of the targets were analyzed by Gene Ontology (GO) and pathway enrichment. A total of 145 active compounds were selected from seven herbal ingredients of QFY. Targets (e.g., MAPT, APP, ACHE, iNOS, and COX‐2) were predicted for the selected active compounds based on the relevance to AD and inflammation. As a validation, fractions were sequentially prepared by aqueous extraction, ethanolic precipitation, and HPLC separation, and assayed for downregulating two key proinflammatory biomarkers iNOS and COX‐2 in lipopolysaccharide‐ (LPS‐) challenged BV‐2 cells by the Western blotting technique. Moreover, the compounds of QFY in 90% ethanol downregulated iNOS in BV‐2 cells but showed no activity against COX‐2 induction. Among the herbal ingredients of QFY, Angelicae Sinensis Radix and Ginseng Radix et Rhizoma contributed to the selective inhibition of iNOS induction. Furthermore, chemical analysis identified ginsenosides, especially Rg3, as antineuroinflammatory compounds. The herbal formula QFY may ameliorate neuroinflammation via downregulating iNOS in microglia.