文章摘要
基于网络药理学研究葛根汤治疗偏头痛的作用机制及实验验证
Study on the Mechanism and Experimental Validation of Gegen Tang in Treating Migraine Based on Network PharmacologySHEN Hao1,WANG Rui Ming2*
投稿时间:2023-08-09  修订日期:2023-08-09
DOI:
中文关键词: 网络药理学  葛根汤  偏头痛  细胞实验  炎症
英文关键词: Network pharmacology  Gegen Tang  Migraine  Cell experiments  inflammation
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中文摘要:
      目的 基于网络药理学探究葛根汤治疗偏头痛的作用机制,并通过细胞实验验证。方法:通过TCMSP平台检索葛根汤的化学物质及药物靶点,通过 Genecard数据库检索偏头痛的疾病靶点。将二者靶点取交集得到葛根汤治疗偏头痛的潜在靶点。构建有效化合物-作用靶点-疾病网络、PPI网络。通过Bioconductor生物信息软件包进行GO功能及KEGG通路富集分析。采用BV-2小胶质细胞进行细胞实验,分为空白对照组(control),模型组(LPS组),葛根汤高(800 μg·mL-1)、低剂量组(400 μg·mL-1)。结果:筛选得到葛根汤治疗偏头痛的潜在有效成分共122个,潜在靶点144个,其中槲皮素、木犀草素、山奈酚等可能是关键成分,STAT3、JUN、IL6等可能是关键靶点。氧化应激反应、DNA信号转录传导、受体结合、细胞因子活性等是葛根汤治疗偏头痛的可能生物学途径。AGE-RAGE、脂质与动脉粥样硬化、TNF、IL-17等信号通路是葛根汤治疗偏头痛的可能信号通路。细胞实验显示,葛根汤水煎液1.6、2.0、4.0 mg·mL-1组细胞存活率均显著降低(P<0.01),葛根汤水煎液0.2、0.4、0.8 mg·mL-1组细胞存活率差异无统计学差异(P>0.05)。Western blot结果表明,与空白对照组比较,模型组IL-6、STAT3、p-STAT3蛋白表达显著升高(P < 0.05)。与模型组比较,葛根汤高、低剂量组均可以显著降低IL-6、STAT3、p-STAT3蛋白的表达(P < 0.05)。结论:葛根汤中的槲皮素、木犀草素、山奈酚等可能通过作用于STAT3、IL-6等靶点调控脂质与动脉粥样硬化通路,从而起到治疗偏头痛的作用。
英文摘要:
      Objective Exploring the mechanism of action of Gegen Tang in treating migraine based on network pharmacology and verifying it through cell experiments.Methods Retrieve the chemical substances and drug targets of Gegen Tang through the TCMSP platform, and search for disease targets of migraine through the Genecard database. Intersecting the two targets to obtain potential targets for treating migraine with Gegen Tang. Construct effective compound target disease network and PPI network. Conduct GO function and KEGG pathway enrichment analysis using Bioconductor bioinformatics software package. Cell experiments were conducted using BV-2 microglial cells, divided into blank control group (control), model group (LPS group), and Gegen Tang Gao (800 μ G · mL-1), low-dose group (400 μ G · mL-1).Results A total of 122 potential effective ingredients and 144 potential targets were screened for the treatment of migraine with Gegen Tang. Quercetin, luteolin, and kaempferol may be key components, while STAT3, JUN, and IL6 may be key targets. Oxidative stress response, DNA signal transcription transduction, receptor binding, cytokine activity, etc. are possible biological pathways for the treatment of migraine with Gegen Tang. AGE-RAGE, lipid and atherosclerosis, TNF, IL-17 and other signal pathways are the possible signal pathways of Gegen Decoction in treating migraine. Cell experiments showed that the survival rate of cells in the 1.6, 2.0, and 4.0 mg · mL-1 groups of Gegen Tang decoction significantly decreased (P<0.01), while there was no statistically significant difference in the survival rate of cells in the 0.2, 0.4, and 0.8 mg · mL-1 groups of Gegen Tang decoction (P>0.05). Western blot results showed that compared with the blank control group, the expression of IL-6, STAT3, and p-STAT3 proteins in the model group was significantly increased (P<0.05). Compared with the model group, the high-dose and low-dose groups of Gegen Tang significantly reduced the expression of IL-6, STAT3, and p-STAT3 proteins (P<0.05).Conclusion Quercetin, luteolin, kaempferol, etc. in Gegen Decoction may play a role in the treatment of migraine by acting on STAT3, IL-6 and other targets to regulate lipid and atherosclerosis pathways.
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