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1. 咸宁市中心医院/湖北科技学院第一附属医院胃肠外科二病区
2. 广东药科大学中药学院
3. 广东药科大学新药研发中心
4. 湖北科技学院药学院
5. 广东省教育厅现代中药重点实验室
6. 国家中医药管理局中药制剂实验室(三级)
纸质出版日期:2021,
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严海冬, 缪文清, 许巧欣, 等. 基于网络药理学的白术-白芍配伍治疗肠易激综合征的作用机制研究[J]. 中国医院用药评价与分析, 2021,21(6):671-677.
YAN Haidong, MIAO Wenqing, XU Qiaoxin, et al. Mechanism of Rhizoma Atractylodes Macrocephala in Compatible with Radix Paeoniae Alba in the Treatment of Irritable Bowel Syndrome Based on Network Pharmacology[J]. 2021,21(6):671-677.
严海冬, 缪文清, 许巧欣, 等. 基于网络药理学的白术-白芍配伍治疗肠易激综合征的作用机制研究[J]. 中国医院用药评价与分析, 2021,21(6):671-677. DOI: 10.14009/j.issn.1672-2124.2021.06.008.
YAN Haidong, MIAO Wenqing, XU Qiaoxin, et al. Mechanism of Rhizoma Atractylodes Macrocephala in Compatible with Radix Paeoniae Alba in the Treatment of Irritable Bowel Syndrome Based on Network Pharmacology[J]. 2021,21(6):671-677. DOI: 10.14009/j.issn.1672-2124.2021.06.008.
目的:基于网络药理学方法
探讨白术-白芍配伍治疗肠易激综合征(irritable bowel syndrome
IBS)的潜在作用机制。方法:借助中药系统药理学数据库与分析平台检索白术、白芍的化学成分和作用靶点
通过Uniprot数据库查询靶点对应的基因
同时通过Gene Cards数据库、疾病相关的基因与突变位点数据库以及治疗靶标数据库等获得IBS疾病靶点。将白术-白芍药对作用靶点基因与疾病靶点进行韦恩交集分析
使用软件Cytoscape 3.7.2构建"药对-活性成分-作用靶点"网络
借助String数据库进行蛋白质-蛋白质相互作用分析;同时
使用Metascape数据库平台
对基因靶点进行基因本体(gene ontology
GO)功能富集分析、京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes
KEGG)通路富集分析。结果:通过筛选
白术-白芍药对共获得20个活性成分
对应89个潜在作用靶点; IBS通过去重后获得1 774个疾病靶点
比对后存在55个交集靶点。其中
山柰酚、3β-乙酰氧基、β-谷甾醇、儿茶素、8β-乙氧基白术内酯Ⅲ、芍药苷及谷甾醇等20个主要活性成分可能通过AKT1、IL-6、TNF、PTGS2、JUN、CAT及CASP3等55个潜在关键靶点作用于IBS。GO功能富集分析共得到GO条目47个(P≤0.01)
其中生物过程条目20个
细胞组成条目9个
分子功能条目18个
主要涉及有毒物质应激反应、血液循环、活性氧代谢过程及异源生物应激反应等。KEGG通路富集分析筛选得到15条信号通路(P≤0.01)
包括糖尿病并发症中的AGE-RAGE信号通路、钙信号通路及HIF-1信号通路等信号通路。结论:通过网络药理学分析发现
白术-白芍药对中的山柰酚、芍药苷、8β-乙氧基白术内酯Ⅲ和β-谷甾醇等潜在活性成分主要通过调节AGE-RAGE信号通路、钙离子信号通路等作用机制发挥治疗IBS的作用。
OBJECTIVE: To analyze the potential mechanism of rhizoma atractylodes macrocephala in compatible with radix paeoniae alba in the treatment of irritable bowel syndrome( IBS) based on network pharmacology.METHODS: The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform( TCMSP) was retrieved for the chemical components and effect targets of rhizoma atractylodes macrocephala and radix paeoniae alba
and the genes corresponding to the targets were queried by Uniprot database
the IBS disease targets were obtained through GeneCards database
disease-related genes and mutation loci database and therapeutic target database. Wayne intersection analysis was performed on drug pair action target genes and disease targets
the Cytoscape 3. 7. 2 software was adopted to construct a "drug pair-active component-effect target"network and the String database was used to analyze protein-protein interactions. Meanwhile
the gene ontology( GO) functional enrichment analysis and the Kyoto encyclopedia of genes and genomes( KEGG) pathway enrichment analysis were performed by using the Metascape database platform. RESULTS: Through screening
totally 20 kinds of active components corresponding to 89 potential effect targets were obtained from the rhizoma atractylodes macrocephala-radix paeoniae alba pair; 1 774 disease targets were obtained by IBS after de-duplication
and 55 intersecting targets existed after comparison. Among them
20 kinds of major active components
including kaempferol
3β-acetoxy
β-sitosterol
catechin
8β-ethoxy atractylolactone Ⅲ
paeoniflorin and sitosterol
might act on IBS through 55 potential key targets
including AKT1
IL-6
TNF
PTGS2
JUN
CAT and CASP3. Totally 47 GO items were obtained from GO functional enrichment analysis( P ≤0. 01)
of which 20 items were biological process
9 items were cell constituent
18 items were molecular function
mainly involving toxic substance stress response
blood circulation
reactive oxygen metabolic process and xenobiotic stress response. Totally 15 signaling pathways were obtained from KEGG pathway enrichment analysis( P≤0. 01)
including AGE-RAGE signaling pathway
calcium signaling pathway and HIF-1 signaling pathway in diabetic complications.CONCLUSIONS: The network pharmacological analysis revealed that the potentially active components of rhizoma atractylodes macrocephala-radix paeoniae alba pair including kaempferol
paeoniflorin
8β-ethoxylated atractylolactoneⅢ and β-sitosterol mainly plays the therapeutic role in the treatment of IBS by regulating the AGE-RAGE signaling pathway
calcium signaling pathway and other mechanisms of action.
白术-白芍药对肠易激综合征网络药理学作用机制
Rhizoma atractylodes macrocephala-radix paeoniae albaDrug pairIrritable bowel syndromeNetwork pharmacologyMechanism
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