摘要
目的运用网络药理学结合试验验证探讨柴胡疏肝散治疗肝郁气滞型心因性勃起功能障碍(Psychogenic erectile dysfunction,p ED)的可能分子机制。方法通过网络药理学筛选出柴胡疏肝散在治疗心因性ED中发挥主要作用的成分、靶点及通路,将符合纳入标准的8例肝郁气滞型p ED患者随机分为柴胡舒肝散组和安慰剂组,各4例,观察治疗前后两组的血清蛋白组学的差异。结果网络药理学及蛋白组学的分析结果提示,柴胡疏肝散治疗肝郁气滞型p ED的作用靶点为丝氨酸/苏氨酸蛋白激酶1(Serine/Threonine protein kinase 1,AKT1)、白细胞介素6(Interleukin6,IL-6)、丝裂原活化蛋白激酶3(Mitogen-activated protein kinase 3,MAPK3)、肿瘤坏死因子(Tumor necrosis factor,TNF)、血管内皮生长因子A(Vascular endothelial growth factor A,VEGFA)和一氧化氮合酶3(Nitric oxide synthase typeⅢ,NOS3)等;基因本论(Gene Ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and Genomes,KEGG)通路分析发现其参与了细胞过程、生物调节等,涉及到了缺氧诱导因子-1(Hypoxia inducible factor-1,HIF-1)信号通路、前列腺癌信号通路、p53信号通路。结论本研究揭示了柴胡疏肝散可通过多成分、多靶点、多通路发挥治疗肝郁气滞型p ED的作用特点,其活性成分槲皮素、异鼠李素、柚皮素、川陈皮素,作用于AKT1、IL6、MAPK3、TNF、VEGFA、NOS3等靶点,进而影响HIF-1信号通路、前列腺癌信号通路、p53信号通路等多个信号通路,产生细胞增殖和凋亡、炎性反应、氧化还原等作用,为进一步阐释其作用机制奠定了基础。
Objective To analyze the possible molecular mechanism of Chaihu Shugan San in the treatment of psychogenic erectile dysfunction(p ED)caused by liver stagnation and qi stagnation using the network pharmacology and experimental validation.Methods The main components,targets,and pathways of Chaihu Shugan San in the treatment of p ED were screened by network pharmacology.Eight patients with p ED caused by liver stagnation and qi stagnation,who met the inclusion criteria were randomly divided into two groups including the Chaihu Shugan San group and the placebo group,4 cases each group,and the differences in serum proteomics between the two groups were observed before and after treatment.Results The results of network pharmacology and proteomics analysis suggested that the therapeutic targets of Chaihu Shugan San in the treatment of p ED caused by liver stagnation and qi stagnation were serine-threonine-protein kinase 1(AKT1),interleukin 6(IL-6),mitogen-activated protein kinase 3(MAPK3),tumor necrosis factor(TNF),vascular endothelial growth factor A(VEGFA),and nitric oxide synthase type III(NOS3),etc.The GO enrichment analysis and KEGG pathway analysis revealed that HIF-1 signaling pathway,prostate cancer signaling pathway,p53 signaling pathway,etc.might participate in this pathological process.Conclusion Chaihu Shugan San can play a role in the treatment of p ED caused by liver stagnation and qi stagnation through multiple components,multiple targets and pathways.The active ingredients such as quercetin,isorhamnetin,naringenin and Chuan Chenpi act on AKT1,IL6,MAPK3,TNF,VEGFA,NOS3 and other targets,then affects the HIF-1 signaling pathway,prostate cancer signaling pathway,p53 signaling pathway and other signaling pathways to produce cell proliferation and apoptosis,inflammatory response and redox,all which lay the basis for further elucidation of its mechanism of action.
作者
林家棋
曹军
董叶
赵一凡
李富豪
叶艳
马紫阳
常德贵
张培海
Lin Jiaqi;Cao Jun;Dong Ye;Zhao Yifan;Li Fuhao;Ye Yan;Ma Ziyang;Chang Degui;Zhang Peihai(TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610075 Sichuan,China;Taihe County People's Hoepital,Fuyang 236699 Anhui,China;Chengdu University of Traditional Chinese Medicine,Chengdu 610072 Sichuan,China;The Traditional Chinese Medicine Hospital of Longquanyi,Chengdu,Chengdu 610100 Sichuan,China)
出处
《中国男科学杂志》
CAS
CSCD
2022年第6期84-93,共10页
Chinese Journal of Andrology
基金
四川省科技厅重点研发项目(2019YFS0184)基金资助
四川省中医药文化协同发展研究中心(2021XT111)基金资助。
关键词
柴胡疏肝散
勃起功能障碍
性功能障碍
心因性
蛋白组学
肝郁气滞
Chaihu Shugan San
erectile dysfunction
sexual dysfunctions
psychological
proteomics
liver depression and qi stagnation
