基于网络药理学筛选和实验验证的山奈酚对慢性萎缩性胃炎大鼠 hedgehog 信号通路的影响。
Effect of kaempferol on hedgehog signaling pathway in rats with --chronic atrophic gastritis - Based on network pharmacological screening and experimental verification.
机构信息
College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
出版信息
Biomed Pharmacother. 2022 Jan;145:112451. doi: 10.1016/j.biopha.2021.112451. Epub 2021 Nov 25.
OBJECTIVE
The effect of active ingredients of Chaishaoliujun Decoction (CD) on chronic atrophic gastritis (CAG) was screened by network pharmacological method and verified by preliminary experiment.
METHODS
Firstly, the active ingredients and drug targets of CD were retrieved in TCMSP database; CAG-related targets from PharmGkb, OMIM, GeneCards and DrugBank databases were collected as well. Secondly, the drug targets and disease targets were mapped to obtain the intersection targets. PPI network and active ingredient-common target network were constructed for the intersection targets obtained and KEGG enrichment analysis was also carried out. Finally, the core active ingredient (kaempferol), effective targets (IL-1β、IL-6) and hedgehog signaling pathway were verified by animal experiments.
RESULTS
There were 137 active ingredients, 243 potential target so and 48 intersection targets with CAG in CD. 147 KEGG enrichment pathways were obtained, mainly involving JAK/STAT signaling pathway, PI3K/Akt signaling pathway, hedgehog signaling pathway, etc. The results of animal experiments showed: The content of IL-1β and IL-6 in model group was significantly increased compared with the normal group, while the mRNA and protein expressions of Shh, Ptch1 and Gli1 were also significantly decreased (P < 0.05); compared with model group, the content of IL-1β and IL-6 in the vitacoenzyme group, the CD group and the kaempferol group were significantly decreased, while the mRNA and protein expressions of Shh, Ptch1 and Gli1 were significantly increased (P < 0.05).
CONCLUSION
Kaempferol, the active ingredient of CD, could reduce the levels of IL-6 and IL-1β by regulating hedgehog signaling pathway so as to play a role in the treatment of CAG. Hence this paper could provide the methodological basis and theoretical basis for further revealing the pharmacological mechanism of CD.
目的
采用网络药理学方法筛选柴芍六君汤（CD）的有效成分对慢性萎缩性胃炎（CAG）的作用，并通过初步实验进行验证。
方法
首先，在 TCMSP 数据库中检索 CD 的活性成分和药物靶点；从 PharmGkb、OMIM、GeneCards 和 DrugBank 数据库中收集 CAG 相关靶点。其次，将药物靶点和疾病靶点进行映射，获得交集靶点。构建交集靶点的 PPI 网络和活性成分-共同靶点网络，并进行 KEGG 富集分析。最后，通过动物实验验证核心活性成分（山奈酚）、有效靶点（IL-1β、IL-6）和 Hedgehog 信号通路。
结果
CD 中有 137 种活性成分、243 个潜在靶点和 48 个与 CAG 的交集靶点。获得了 147 条 KEGG 富集通路，主要涉及 JAK/STAT 信号通路、PI3K/Akt 信号通路、Hedgehog 信号通路等。动物实验结果表明：与正常组相比，模型组中 IL-1β和 IL-6 的含量显著增加，而 Shh、Ptch1 和 Gli1 的 mRNA 和蛋白表达也显著降低（P<0.05）；与模型组相比，维酶素组、CD 组和山奈酚组的 IL-1β和 IL-6 含量显著降低，而 Shh、Ptch1 和 Gli1 的 mRNA 和蛋白表达显著升高（P<0.05）。
结论
CD 的活性成分山奈酚通过调节 Hedgehog 信号通路降低 IL-6 和 IL-1β的水平，从而发挥治疗 CAG 的作用。因此，本研究可为进一步揭示 CD 的药理机制提供方法学依据和理论基础。
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