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药学学报, 2022, 57(3): 716-723 |
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引用本文： |
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杨吾燕, 闫姣姣, 高丽, 秦雪梅. 基于生物信息分析研究黄芩素通过NOX2/STAT1/NF-κB通路抑制LPS诱导的BV-2细胞神经炎症的作用机制[J]. 药学学报, 2022, 57(3): 716-723. |
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YANG Wu-yan, YAN Jiao-jiao, GAO Li, QIN Xue-mei. Baicalein inhibits neuroinflammation via NOX2/STAT1/NF-κB pathway in LPS-induced BV-2 cells based on bioinformatics methods[J]. Acta Pharmaceutica Sinica, 2022, 57(3): 716-723. |
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| 基于生物信息分析研究黄芩素通过NOX2/STAT1/NF-κB通路抑制LPS诱导的BV-2细胞神经炎症的作用机制 |
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| 杨吾燕1,2,3, 闫姣姣1,2,3, 高丽1,2,3*, 秦雪梅1,2,3* |
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1. 山西大学中医药现代研究中心, 山西 太原 030006;
2. 山西大学化学生物学与分子工程教育部重点实验室, 山西 太原 030006;
3. 地产中药功效物质研究与利用山西省重点实验室, 山西 太原 030006 |
| 摘要: |
| 本研究旨在确定黄芩素对脂多糖（lipopolysaccharide，LPS）诱导的BV-2细胞神经炎症的分子机制。采用生物信息分析、分子对接方法预测黄芩素的潜在靶点和作用机制，并使用免疫荧光染色和Western blot技术对关键靶点一氧化氮合酶（inducible nitric oxide synthase，iNOS）和环氧合酶-2 （cyclooxygenase-2，COX-2）、信号转导子和转录激活子1/核因子κB （signal transducer and activator of transcription 1/nuclear factor kappa-B，STAT1/NF-κB）信号通路相关蛋白及其上游调控因子NADPH氧化酶2 （NADPH oxidase-2，NOX2）进行验证，研究黄芩素改善神经炎症的作用机制。结果表明，生物信息分析和分子对接技术预测出iNOS和COX-2为关键靶点，NF-κB信号通路为关键通路。实验验证表明，在LPS诱导的BV-2细胞中，黄芩素能显著降低iNOS和COX-2的表达水平，有效抑制NF-κB和STAT1的磷酸化及NOX2的生成。综上，黄芩素可通过NOX2 （gp91phox/p47phox）/STAT1/NF-κB途径显著抑制LPS诱导的BV-2细胞炎症。 |
| 关键词:
黄芩素
神经炎症
网络药理学
分子对接
作用机制
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| Baicalein inhibits neuroinflammation via NOX2/STAT1/NF-κB pathway in LPS-induced BV-2 cells based on bioinformatics methods |
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| YANG Wu-yan1,2,3, YAN Jiao-jiao1,2,3, GAO Li1,2,3*, QIN Xue-mei1,2,3* |
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1. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China;
2. The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China;
3. The Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Taiyuan 030006, China |
| Abstract: |
| This study identified the exact molecular mechanisms of baicalein on neuroinflammation in lipopolysaccharide (LPS)-induced BV-2 cells. Bioinformatics methods and molecular docking were integrated for predicting the potential targets and mechanisms of baicalein. Immunofluorescence staining and Western blot were used to analyze the predicted key targets [inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2)], the expression level of protein related to signal transducer and activator of transcription 1/nuclear factor kappa-B (STAT1/NF-κB) signaling pathway and its upstream regulator NADPH oxidase-2 (NOX2), and then the mechanism of baicalein in alleviating neuroinflammation was explored. The results showed that iNOS and COX-2 were predicted as the key targets and NF-κB signaling pathway was one of the important pathways by bioinformatics methods and molecular docking. Experimental verification showed that baicalein could significantly reduce the expression of iNOS and COX-2, inhibit the phosphorylation of NF-κB and STAT1 and the production of NOX2 in LPS-induced BV-2 cells. To sum up, baicalein could effectively inhibit the inflammatory reaction in LPS-induced BV-2 cells through regulating NOX2 (gp91phox/p47phox)/STAT1/NF-κB pathway. |
| Key words:
baicalein
neuroinflammation
network pharmacology
molecular docking
mechanism
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| 收稿日期: 2021-09-13
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| DOI: 10.16438/j.0513-4870.2021-1339 |
| 基金项目: 国家自然科学基金资助项目（81603319）；山西省面上青年基金资助项目（201801D221374）。 |
通讯作者: 高丽,Tel:86-351-7018379,E-mail:gaoli87@sxu.edu.cn;秦雪梅,Tel:86-351-7011501,E-mail:qinxm@sxu.edu.cn
Email: gaoli87@sxu.edu.cn;qinxm@sxu.edu.cn |
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