目的 基于入血成分和网络药理学研究策略,探讨连夏消痞颗粒治疗功能性消化不良的潜在药效物质基础。方法 采用超高效液相联用四极杆飞行时间质谱(UPLC-Q-TOF-MS)结合Simca-P软件对连夏消痞颗粒大鼠给药后血浆及尿液中原型成分进行定性解析。采用TCMSP、OMIM等在线数据库搜集化合物及疾病靶点,取交集后构建蛋白互作网络,筛选核心靶点并进行通路富集。采用Cytoscape软件构建活性成分-靶点-通路网络图;采用分子对接,对排名靠前的化学成分与靶点的相互关系进行验证,为体内药效物质基础研究提供参考。结果 共鉴定连夏消痞颗粒入血成分46个,主要为黄酮类化合物,其次是生物碱类化合物;疾病-化合物共有靶点105个,蛋白互作网络筛选出核心靶点43个。通路富集为胆碱能突触、PI3K-Akt信号通路、胰岛素分泌、钙离子信号通路、钙吸收、胆汁分泌等信号通路。分子对接结果显示,黄酮类及生物碱类等化合物与ESR1、IL2、AMY1A、ABCB1、VEGFR、ABCG2、NOS3、RELA、NFκB1等核心靶点对接活性较好(平均得分值＞100)。结论 连夏消痞颗粒中的橙皮苷、柚皮苷、木犀草苷、甘草苷、黄芩苷、6-姜辣素、黄连碱、表小檗碱、小檗碱、巴马汀等可能为其潜在药效物质基础,通过调节胃肠动力、提高内脏敏感性、抗焦虑抑郁等方面,对功能性消化不良起到调节作用。
Abstract
OBJECTIVE To investigate the potential pharmacological material basis of Lianxia Xiaopi Granules for the treatment of functional dyspepsia based on the prototype components and network pharmacology strategy. METHODS UPLC-Q-TOF-MS combined with Simca-P software was used to qualitatively analyze the prototype components in plasma and urine of rats given Lianxia Xiaopi Granules, and online databases such as TCMSP and OMIM were used to collect compounds and disease targets. After taking the intersection, a protein interaction network was constructed to screen core targets and conduct pathway enrichment. Cytoscape was used to construct an active ingredient-key targets-pathway network, and molecular docking was used to verify the relationship between the top chemical components and targets, to provide a reference for the basic research of the drug effect in the body. RESULTS A total of 46 prototypical components were identified, most of which were flavonoids, followed by alkaloids; 105 disease-compounds targets were found, and 43 core targets were screened out by protein interaction network. The pathway was enriched in cholinergic synapses, PI3K-Akt signaling pathway, insulin secretion, Ca2+ signaling pathway, calcium absorption, bile secretion and other signaling pathways. The results of molecular docking showed that compounds such as flavonoids and alkaloids had good docking activity (average score value >100) with core targets such as ESR1, IL2, AMY1A, ABCB1, VEGFR, ABCG2, NOS3, RELA, and NFκB1. CONCLUSION Hesperidin, naringin, luteolin, liquiritin, baicalin, 6-gingerol, coptisine, epiberberine, berberine, palmatine, etc. in Lianxia Xiaopi Granules may be the potential material basis of the drug effect, which can treat functional dyspepsia by regulating gastrointestinal motility, visceral hypersensitivity, anxiety and depression, digestion, and metabolism.
关键词
连夏消痞颗粒 /
功能性消化不良 /
超高效液相联用四极杆飞行时间质谱 /
药效物质基础 /
分子对接
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Key words
Lianxia XiaoPi Granules /
functional dyspepsia /
UPLC-Q-TOF-MS /
pharmacophore basis /
molecular docking
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脚注
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基金
国家科技重大专项资助(2017ZX09301005)
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