川芎-丹参药对主要药理成分的网络药理学和指纹图谱研究

Network pharmacology of main pharmacological components of Chuanxiong-Danshen drug pair and its fingerprints

  • 摘要:
    目的 基于网络药理学研究方法挖掘川芎-丹参药对的活性成分、靶点和对疾病的作用机制。
    方法 以川芎和丹参为关键词, 在中药系统药理学分析平台(TCMSP)数据库中检索川芎和丹参的活性成分、靶点和对应疾病数据,构建多层次多靶点网络图,进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,探讨川芎-丹参药对的作用机制,通过高效液相色谱法(HPLC)指纹图谱检测川芎-丹参药对的活性成分。
    结果 “药物-成分-靶点-疾病”网络中包括2种药物、15个成分、72个靶点、187种疾病。川芎-丹参药对的关键靶点包括醛糖还原酶(AKR1B1)、碳酸酐酶2(CA2)、碳酸酐酶1(CA1)、乙醛脱氢酶2(ALDH2)、前列腺素G/H合成酶1(PTGS1)、表皮生长因子受体(EGFR)、基质金属蛋白酶9(MMP9)、基质金属蛋白酶2(MMP2)、去甲肾上腺素转运体(SLC6A2)和腺苷受体A1(ADORA1), 涉及疼痛、心血管疾病、阿尔茨海默病、前列腺癌、脑损伤等多种疾病。GO富集分析共得到条目223条,包括生物过程165条、分子功能30条、细胞组成28条; KEGG富集分析共得到78条通路,包括癌症通路、神经活性配体-受体相互作用、PI3K-Akt信号通路、乙肝信号通路等。HPLC指纹图谱检测出谷甾醇、川芎嗪、丹参醇B、鼠尾草酚酮、木犀草素、川芎哚这6个色谱峰。
    结论 川芎-丹参药对中,多个活性成分作用于多个靶点,对疼痛、心血管疾病、阿尔茨海默病、前列腺癌、脑损伤等具有治疗作用。

     

    Abstract:
    Objective To explore the active ingredients, targets and the mechanism of action of Chuanxiong-Danshen drug pair based on the network pharmacological research method.
    Methods Taking Chuanxiong and Danshen as key words, their active ingredients, targets and corresponding disease data were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the multi-layer and multi-target network map was constructed to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis, so as to explore the mechanism of action of Chuanxiong-Danshen drug pair. Determination of active components of Chuanxiong-Danshen by high-performance liquid chromatography (HPLC) fingerprint.
    Results The "drug-composition-target-disease" network included 2 kinds of drugs, 15 ingredients, 72 targets, and 187 diseases. Key targets included aldo-keto reductase family 1 member B1 (AKR1B1), carbonic anhydrase 2 (CA2), carbonic anhydrase 1 (CA1), acetaldehyde dehydrogenase 2 (ALDH2), prostaglandin G/H synthetase 1 (PTGS1), epidermal growth factor receptor (EGFR), matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 2 (MMP2), norepinephrine transporter (SLC6A2) and adenosine receptor A1 (ADORA1). It involved in pain, cardiovascular disease, Alzheimer's disease, prostate cancer and cerebral injury, etc. There were 223 GO enrichment items, including 165 biological processes, 30 molecular functions and 28 cell compositions. A total of 78 pathways were identified by KEGG enrichment analysis, including cancer pathway, neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway, hepatitis B signaling pathway, etc. Six peaks of sitosterol, ligustrazine, tanshinol B, carnophenol one, luteolin and Perlolyrine were detected by HPLC fingerprint.
    Conclusion In Chuanxiong-Danshen drug pair, active ingredients act on multiple targets, and has a therapeutic effect on pain, cardiovascular disease, Alzheimer's disease, prostate cancer, brain injury and other diseases.

     

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