基于网络药理学分析孙河运用通窍明目Ⅳ号治疗青光眼的视神经保护机制

Network Pharmacology-based Analysis of the Optic Nerve Protective Mechanism of Tongqiao Mingmu Ⅳ Formula Applied by SUN He on Glaucoma

目的基于网络药理学研究方法,挖掘孙河教授运用通窍明目Ⅳ号(柴胡、郁金、丹参、石菖蒲、葛根、当归)防治青光眼患者视神经损害的作用机制。方法应用TCMSP数据库获取通窍明目Ⅳ号的主要活性化合物及相关靶蛋白信息;利用Uniport数据库获取靶蛋白对应基因;在Genecards数据库获取青光眼的对应靶点;通过String网站绘制“中药-疾病”共同靶点的PPI网络;运用Cytoscape构建中药-化合物-靶基因-疾病可视化网络图;通过DAVID和KEGG数据库对中药-疾病共同靶点进行GO功能注释和KEGG富集分析。结果共获得通窍明目Ⅳ号85种活性化合物及240个潜在靶点,获得青光眼高相关度靶点956个,得到中药-疾病共同靶点69个。发现槲皮素和山柰酚可能为通窍明目Ⅳ的主要有效化合物。药物疾病共同靶点分别富集在24个GO基因功能与12条KEGG信号通路。结论通窍明目Ⅳ号可能通过调控PI3K-Akt、HIF-1、p53、Jak-STAT等信号通路,影响细胞外区域、溶酶体等细胞组分,调节细胞因子活性及蛋白结合等分子功能,进而影响细胞凋亡、药物反应、血管生成等生物学过程,发挥视神经保护作用,从而控制青光眼患者的视神经损害,保存患者的视功能。

Objective To explore the mechanism of Tongqiao Mingmu Ⅳ formula applied by Professor SUN He in the prevention and treatment of optic nerve damage in glaucoma patients by network pharmacology method. Methods The main active compounds and related target proteins of Tongqiao Mingmu Ⅳ formula were obtained from TCMSP database. The corresponding genes of target proteins were found in Uniport database. Genecards database was used to obtain the corresponding targets of glaucoma. PPI network of TCM-disease target was drawn through String website,Cytoscape was used to construct a visual network of TCM-compound-target. Go function annotation and KEGG enrichment analysis of common targets of TCM-disease were carried out by DAVID and KEGG database. Results A total of 85 active compounds and 240 potential targets of Tongqiao Mingmu Ⅳ formula were obtained,956 highly correlated targets of glaucoma and 69 common targets of TCM-disease were also found. It was discovered that quercetin and kaempferol may be the main effective compounds for Tongqiao Mingmu Ⅳ formula. The common targets of drug-diseases were enriched in 24 GO gene functions and 12 KEGG signaling pathways. Conclusion Tongqiao Mingmu Ⅳ formula may affect the extracellular area, lysosomes, and other cellular components by regulating PI3K-Akt,HIF-1,p53,Jak-STAT signaling pathways. It also regulates molecular functions,such as cytokine activity and protein binding,which in turn affects the biological processes(cell apoptosis,drug response,angiogenesis,etc.),thereby plays a protective effect on the optic nerve,reduces the optic nerve damage of patients with glaucoma and preserves the patients’ visual function.