基于网络药理学和分子对接的逍遥散治疗肝癌并抑郁症的潜在机制探讨

Exploration potential mechanism of Xiaoyao Powder in treatment of liver cancer complicated with depression based on network pharmacology and molecular docking

目的通过网络药理学和分子对接方法,探讨逍遥散治疗肝癌并抑郁症的潜在机制。方法通过TCMSP数据库,以逍遥散组方中药中文名称为检索词,设置口服生物利用度(OB)>30%和类药性(DL)>0.18为筛选条件获取中药活性成分与靶点,从GeneCards数据库中获取肝癌和抑郁症疾病相关靶点,并将疾病靶点与药物成分靶点相互交集,获取共同交集靶点后,导入DAVID数据库进行京都基因与基因组百科全书(KEGG)通路和基因本体(GO)功能的富集分析,并进行分子对接验证活性成分与关键靶点的亲和力。结果获得逍遥散161个活性成分和238个靶点,而疾病靶点共计11204个;成分靶点和疾病靶点取交集得共同靶点69个;KEGG通路富集在AGEs-RAGE、癌症、HIF-1等信号通路;分子对接显示核心成分3β-乙酰氧基苍术酮与白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)等靶点结合活性良好。结论逍遥散主要通过3β-乙酰氧基苍术酮介导ILIB、TNF、BCL2等靶标,调节AGEs-RAGE、癌症等信号通路,发挥抗炎、免疫调控、促进细胞凋亡等作用,从而改善肝癌和抑郁症的症状。

Objective To explore the underlying mechanisms of Xiaoyao Powder in treatment of liver cancer with depression,utilizing the methodologies of network pharmacology and molecular docking.Methods The TCMSP database was used to obtain the effective active components and targets of Chinese herbal medicine by setting oral bioavailability(OB)>30%and drug like(DL)>0.18 as the screening conditions.The disease-related targets were obtained from the GeneCards database,and the disease targets and drug targets were intersected to obtain the common intersection targets,which were imported into the DAVID database for KEGG pathway and GO function enrichment analysis.Molecular docking was performed to verify the affinity of active ingredients and key targets.Results A comprehensive analysis yielded a total of 161 therapeutically active components and 661 targets associated with Xiaoyao Powder,with 11204 disease targets in total.KEGG pathway enrichment was observed in AGE-RAGE signaling pathway,cancer-related targets,and HIF-1,among others.Molecular docking analysis revealed that the core component 3β-acetoxyatractylon exhibited favorable binding affinity towards the identified targets such as interleukin-6 and tumor necrosis factor.Conclusion Xiaoyao Powder primarily exerts its effects through 3β-acetoxyatractylon mediating targets like interleukin-6,tumor necrosis factor,and anti-apoptotic genes,regulating pathways such as AGE-RAGE and cancer.It plays roles in anti-inflammation,immune regulation,and promoting apoptosis,thereby improving the symptoms of liver cancer and depression.