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论颅痛通颗粒中天然植物药治疗脑出血的基因网络作用机制

Mechanism of gene network in the treatment of intracerebral hemorrhage by natural plant drugs in Lutong granules.

机构信息

Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.

Department of Neurosurgery, The first Hospital of Kunming, Kunming, Yunnan Province, China.

出版信息

PLoS One. 2022 Nov 28;17(11):e0274639. doi: 10.1371/journal.pone.0274639. eCollection 2022.

Abstract

PURPOSE

To study the effects of Lu-tong Granules (LTG) in ICH etermine the underlying mechanism of molecular network.

METHODS

Modern bioinformatics and network pharmacology methods were used to predict molecular network mechanisms between ICH and LTG. Animal experiments were carried out to verify the effect of LTG for the treatment of ICH, combined with behavior test and morphologic detection.

RESULTS

Forty-three active components in LTG and involved 192 gene targets were identified successfully. Moreoner, they were intersected with 1132 genes of ICH,88 intersection targets were obtained. subsequently, Cytoscape was used to screen Hub genes, in which,6 core molecules, including AKT1, IL6, VEGFA, CASP3, JUN and MMP9 were recognized. Furthermore, we constructed Six core compounds by " disease-drug-active ingredient-target-KEGG " (D-D-A-T-K) network, showed including quercetin, luteolin, β sitosterol, stigmasterol, kaempferol and formononetin, and PPI protein network interaction showed that AKT1:OS3 and CNA2:DKN1A had the highest correlation. Whereas the enrichment of GO and KEGG indicated that LTG was most likely to play a therapeutic role in ICH through AGE-RAGE signaling pathway in diabetic complications. Integrated analysis also showed that the first 10 pathways of KEGG are integrated into 59 genes, among which 6 core genes are closely involved. Lastly, molecular docking showed that there was a good binding activity between the core components and the core genes, and animal experiments confirmed effect of LTG in the treatment of ICH, by using TTC staining and behavior test.

CONCLUSION

LTG are effective for the treatment of ICH, the underlying mechanism could be involved in gene network including anti-inflammatory response, nerve repair, analgesia, anti-epilepsy and other aspects.

摘要

目的

研究路通颗粒(LTG)治疗脑出血(ICH)的作用,确定分子网络的潜在机制。

方法

采用现代生物信息学和网络药理学方法预测 ICH 与 LTG 之间的分子网络机制。通过动物实验结合行为学测试和形态学检测,验证 LTG 治疗 ICH 的效果。

结果

成功鉴定出 LTG 中的 43 种活性成分,涉及 192 个基因靶点。此外,它们与 ICH 的 1132 个基因相互作用,得到 88 个交集靶点。随后,使用 Cytoscape 筛选出 Hub 基因,其中包括 AKT1、IL6、VEGFA、CASP3、JUN 和 MMP9 等 6 个核心分子。此外,我们通过“疾病-药物-活性成分-靶标-KEGG(D-D-A-T-K)”网络构建了 6 个核心化合物,包括槲皮素、木樨草素、β-谷甾醇、豆甾醇、山奈酚和芒柄花素,PPI 蛋白网络相互作用显示 AKT1:OS3 和 CNA2:DKN1A 相关性最高。GO 和 KEGG 的富集分析表明,LTG 很可能通过糖尿病并发症的 AGE-RAGE 信号通路发挥治疗 ICH 的作用。综合分析还表明,KEGG 的前 10 条通路整合到 59 个基因中,其中 6 个核心基因密切参与。最后,分子对接显示核心成分与核心基因之间具有良好的结合活性,动物实验通过 TTC 染色和行为学测试证实了 LTG 治疗 ICH 的效果。

结论

LTG 对 ICH 治疗有效,其作用机制可能涉及包括抗炎反应、神经修复、镇痛、抗癫痫等多方面的基因网络。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aeca/9704616/0984fe3cce42/pone.0274639.g001.jpg

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