基于网络药理学和分子对接分析红景天抑制手术应激过程中CRH、GC释放的机制OACSTPCD
Analysis of mechanisms of Rhodiola rosea in inhibiting the release of CRH and GC during surgical stress based on network pharmacology and molecular docking
目的 基于网络药理学和分子对接分析红景天抑制手术应激过程中促肾上腺皮质激素释放激素(CRH)、糖皮质激素(GC)释放的有效活性成分及相关靶基因,并探讨其可能的机制.方法 使用中药系统药理学数据库、STRING数据库检索红景天的有效活性成分并分析其药物靶基因,NCBI数据库、OMIM 数据库分别检索手术应激、CRH和GC的靶基因,二者取交集后得到红景天降低手术应激过程中CRH、GC的核心靶基因,进行GO功能和KEGG通路富集分析.使用Cytoscape软件绘制蛋白质相互作用网络(PPI)图,根据degree值获得排名前五的核心靶基因,采用分子对接方法分析其与红景天有效活性成分的结合能.结果 筛选后得到红景天有效活性成分10个及其药物靶基因191个,其中degree值排名前三的有效活性成分分别为槲皮素、山柰酚和木犀草素.共得到手术应激相关靶基因118个、CRH相关靶基因44个、GC相关靶基因502个,与药物靶基因取交集后获得核心靶基因16个.GO功能分析结果显示,核心靶基因富集在生物过程136个、细胞成分6个、分子功能15个;KEGG通路分析结果显示,核心靶基因主要富集在高级糖基化终产物—高级糖基化终产物受体(AGE/RAGE)信号通路、缺氧诱导因子1(HIF-1)信号通路和人类巨细胞病毒感染等.PPI图中degree值排名前五的核心靶基因分别为前列腺素—内过氧化物合酶2(PTGS2)、肿瘤坏死因子(TNF)、白细胞介素6(IL-6)、分泌磷蛋白1(SPP1)、肿瘤蛋白p53基因(TP53).槲皮素、山柰酚、木犀草素与PTGS2、IL-6、SPP1、TP53均具有较强的结合作用(结合能均≤-5 kcal/mol).结论 红景天可通过其活性成分槲皮素、山柰酚、木犀草素调节PTGS2、IL-6、SPP1、TP53表达而抑制手术应激过程中CRH、GC释放,其机制可能与AGE/RAGE信号通路有关.
Objective To investigate the active ingredients,related targets,and potential mechanism of Rhodiola rosea in reducing the levels of corticotropin-releasing hormone(CRH)and glucocorticoid(GC)during surgical stress based on network pharmacology and molecular docking.Methods The TCMSP database and STRING database were em-ployed to obtain the active ingredients of Rhodiola Rosea and the associated target genes.NCBI database and OMIM data-base were searched for the target genes of surgical stress,CRH,and GC,respectively.The core target genes of CRH and GC in the process of Rhodiola Rosea reducing surgical stress were obtained after the intersection.GO and KEEG analyses were further conducted based on the core targets.Cytoscape software was used to construct the protein-protein interaction(PPI)network,and the top five core target genes were obtained according to the degree value.The binding energy of core target genes with the active ingredients of Rhodiola rosea was analyzed using molecular docking.Results After the screening,we identified 10 active compounds of Rhodiola rosea and 191 associated target genes.The top three effective ac-tive ingredients with the highest degree values were quercetin,kaempferol,and luteolin.A total of 118 target genes relat-ed to surgical stress,including 44 targets related to CRH,and 502 targets related to GC,were obtained.After intersecting with the drug-associated targets,16 core target genes were obtained.GO analysis showed that 136 core target genes were enriched in biological processes,6 in cellular components,and 15 in the molecular function.KEGG pathway analysis showed that the core target genes were mainly enriched in the advanced glycation end products-receptor of advanced glyca-tion end products(AGE-RAGE)signaling pathway,hypoxia-inducible factor-1(HIF-1)signaling pathway,and human cy-tomegalovirus infection.The PPI network consisted of 16 nodes and 93 edges,and the top five core target genes were pros-taglandin-endoperoxide synthase 2(PTGS2),tumor necrosis factor(TNF),interleukin-6(IL-6),SPP1,and TP53.Quercetin,kaempferol,and luteolin all had strong binding effects with PTGS2,IL-6,SPP1,and TP53(all binding ener-gies≤-5 kcal/mol).Conclusion Rhodiola rosea can reduce the levels of CRH and GC during surgical stress by regulat-ing the expression of PTGS2,IL-6,SPP1,and TP53 through its active ingredients quercetin,kaempferol,and luteolin,and the mechanism may be related to the AGE/RAGE signaling pathway.
胡宝平;卢红燕;王玉梁;王莉;李卫斌;李友安;金天博;袁东亚
西藏民族大学附属医院麻醉科,陕西 咸阳 712082西藏民族大学医学院西藏民族大学医学院||西藏高原相关疾病分子机制与干预研究重点实验室||高原低氧环境与生命健康实验室西藏民族大学附属医院超声科
药学
红景天手术应激促肾上腺皮质激素释放激素糖皮质激素槲皮素前列腺素—内过氧化物合酶2白细胞介素6
Rhodiola roseasurgical stresscorticotropin-releasing hormoneglucocorticoidsquercetinprosta-glandin-endoperoxide synthase 2interleukin-6
《山东医药》 2024 (035)
36-39 / 4
西藏自治区自然科学基金资助项目[XZ2018ZRG-77(Z)].
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