摘要
目的:基于“以方(药)测靶”“靶标关联”“由标知效”“临床验效”和“传承创新”组成的中医方药整体作用靶标研究模式,阐释疏风解毒胶囊(SFJDC)的作用靶标及其发挥抗H1N1病毒感染的新机制。方法:通过动物实验评估SFJDC对H1N1病毒入侵小鼠肺部的影响;采用热蛋白质组学(TPP)技术,对SFJDC在BEAS-2B细胞中的整体作用靶点进行高通量筛选;利用IPA数据库对SFJDC作用靶点与作用靶标、疾病特异性差异表达蛋白质进行关联研究。结果:SFJDC可以降低病毒入侵小鼠肺组织中病毒RNA水平、肺指数,以及炎症因子白细胞介素-1(IL-1)、IL-6和肿瘤坏死因子-α的表达,具有较好的抗病毒功效。筛选获得SFJDC直接作用靶点150个、间接作用靶点66个,其中42个直接作用靶点、19个间接作用靶点与抗病毒功效相关,能够在病毒复制和感染等多个环节发挥干预治疗的作用。此外,SFJDC可能参与调控干扰素信号通路、丝裂原活化蛋白激酶/核转录因子-κB信号通路、Janus酪氨酸激酶-信号转导子和转录激活子信号通路、Toll样受体信号通路和内吞作用通路等多条通路发挥抗病毒功效。结论:建立的“以方(药)测靶”“靶标关联”“由标知效”“临床验效”和“传承创新”组成的中医方药整体作用靶标研究模式从靶标角度阐明了SFJDC发挥抗病毒功效的作用机制。
Objective:Based on the research model for integrative effect of TCM,which consist of modules including"detecting targets of the drug","targeted-regulated molecule association","obtaining the efficacy with the regulated molecule","clinical validation of efficacy",and"inheritance and innovation of TCM",this study gave investigation in the target and new mechanism of the Shufeng Jiedu Capsules(SFJDC)in anti-H1N1 virus infection.Methods:Animal experiments were conducted to assess the effects of SFJDC on H1N1 invasion in the lungs of mice.Thermal proteome profiling was performed for the high-throughput screening of the overall targets of SFJDC in BEAS-2B cells.Additionally,the Ingenuity Pathway Analysis(IPA)database was used for correlation analysis between the targets of SFJDC and disease-specific differentially expressed proteins.Results:SFJDC reduced the levels of viral RNA,lung index,and the expression of inflammatory factors such as interleukin(IL)-1,IL-6,and tumor necrosis factor-alpha in the lung tissue of virus-infected mice,demonstrating significant antiviral efficacy.We identified 150 direct targets and 66 indirect targets of SFJDC,of which 42 direct targets and 19 indirect targets were associated with antiviral efficacy and contributed therapeutically to various aspects of viral replication and infection.Furthermore,SFJDC may be involved in regulating several signaling pathways,including the interferon,mitogen-activated protein kinase/nuclear transcription factor-κB,Janus kinase 1-signal transducer and activator of transcription 1,Toll-like receptor,and endocytosis pathways,thereby exerting its antiviral effects.Conclusion:The"high-throughput target screening-target association-clinical application"research methodology of traditional Chinese medicine clarifies the mechanism underpinning the antiviral efficacy of SFJDC from the perspective of target.
作者
陈恒
王春国
胡子怡
饶沁玲
黄智兴
张鸽
何蓉格
郑浩宇
刘舒阳
申冰清
孙潇寒
李沐萱
陈远
邓欣祺
崔晓兰
CHEN Heng;WANG Chunguo;HU Ziyi;RAO Qinling;HUANG Zhixing;ZHANG Ge;HE Rongge;ZHENG Haoyu;LIU Shuyang;SHEN Bingqing;SUN Xiaohan;LI Muxuan;CHEN Yuan;DENG Xinqi;CUI Xiaolan(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China;Beijing Research Institute of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China;School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China;School of Acupuncture,Moxibustion and Tuina,Beijing University of Chinese Medicine,Beijing 100029,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)
出处
《中国现代中药》
2025年第7期1228-1237,共10页
Modern Chinese Medicine
基金
国家自然科学基金项目(82141206)
北京市自然科学基金项目(7244493)
中国中医科学院中药研究所人才引进项目(ZXKT22059,ZZ16-XRZ-071,ZZ17-YQ-023)
北京中医药大学实验技术(操作规程)标准化研究项目(2023-syjs-01)。
关键词
中药靶标
疏风解毒胶囊
热蛋白质组学
抗病毒
作用机制
Chinese medicine target
Shufeng Jiedu Capsules
thermal proteome profiling
antiviral
mechanism of action
