基于网络药理学和体内试验揭示当归补血汤通过PI3K-AKT信号通路调节免疫抑制的潜在机制  

Revealing potential mechanism of Danggui Buxue decoction in regulating immuno-suppression via PI3K-AKT signaling pathway using network pharmacology and in vivo experiment

作　　者：黄欢 杨萍瑞 李锡锋 桂福星 李禹涛[2] 张莉 柳硕 谢雨霏 杜红旭 毕师诚 曹立亭[1,4] HUANG Huan;YANG Pingrui;LI Xifeng;GUI Fuxing;LI Yutao;ZHANG Li;LIU Shuo;XIE Yufei;DU Hongxu;BI Shicheng;CAO Liting(College ofVeterinary Medicine,Southwest University,Rongchang,Chongqing 402460,China;Institute of Animal Husbandry,Weifang Academy of Agricultural Sciences,Weifang,Shandong 261071,China;Hanzhong Animal Disease Prevention and Control Center,Hanzhong,Shannri 723099,China;Institute of Traditional Chinese Veterinary Medicine,Southwest University,Rongchang,Chongqing 402460,China)

机构地区：[1]西南大学动物医学院,重庆荣昌402460 [2]潍坊市农业科学院畜牧研究所,山东潍坊261071 [3]汉中市动物疫病预防控制中心,陕西汉中723099 [4]西南大学中兽医药研究所,重庆荣昌402460

出　　处：《中国兽医学报》2025年第2期350-361,共12页Chinese Journal of Veterinary Science

基　　金：国家生猪技术创新中心资助项目(NCTIP-XD/C17);重庆市科技创新与应用发展专项重点资助项目(cstc2019jsccx-lyjsBX0003,cstc2021jscx-lyjsAX0008);重庆市科技局自然科学基金资助项目(CSTB2022NSCQ-MSX0470)。

摘　　要：当归补血汤(Danggui Buxue decoction, DBD)作为经典的益气补血名方,实验室前期研究已表明其具有成为口服免疫增强剂的潜力。然而,关于DBD的免疫调节作用机制尚缺乏深入研究,尤其是免疫抑制状态下的免疫保护作用机制尚不清楚。本研究旨在通过网络药理学结合动物试验探讨DBD治疗免疫抑制性疾病的作用机制。利用网络药理学方法,获得DBD治疗免疫抑制性疾病的有效成分、核心靶点和信号通路;在此基础上,建立环磷酰胺诱导的小鼠免疫抑制模型,进行qRT-PCR、ELISA、Western blot试验验证网络药理学预测的主要靶点和信号通路,并利用HPLC-MS鉴定DBD的有效成分。结果表明,DBD治疗免疫抑制性疾病的关键有效成分包括槲皮素、山奈酚、刺芒柄花素等成分;核心靶点涉及TP53、RELA、TNF、AKT1、IL-6;KEGG通路富集分析表明,PI3K-AKT可能在DBD治疗免疫抑制性疾病中起关键作用。分子对接验证各核心靶点与对应化合物之间均有较好的结合活性。动物试验表明,DBD通过下调PI3K-AKT信号通路的表达发挥治疗作用。综上所述,DBD可能以槲皮素为代表的天然活性成分通过调控PI3K-AKT信号通路相关蛋白的表达治疗免疫抑制性疾病。Danggui Buxue decoction(DBD)is a classic prescription with immunomodulatory and hematopoietic effects.Previous studies have shown the DBD has potential to be used as an oral im-mune booster.However,its immunomodulatory effects and mechanism of action have not been thoroughly studied,especially the protective mechanism of immunomodulatory regulation in the state of immunosuppressive is still unclear.The aim of this study was to explore the protective mechanism of DBD in the immunosuppressive state using network pharmacology combined with animal experiments verification.The active components,core targets and signaling pathways of DBD in treating immunosuppression were obtained using network pharmacology tools.On this ba-sis,the active components of DBD were identified using HPLC-MS,and in vivo studies were con-ducted at the same time.The key active components of DBD obtained using network pharmacology included quercetin,kaempferol and formononetin.The core targets included TP53,RELA,TNF,AKT1,and IL-6.KEGG pathway enrichment analysis showed that phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT)may play an important role in the treatment of immunosuppres-sive diseases using DBD.Molecular docking confirmed that each core target had good binding activ-ity with its corresponding compounds.Animal experiments showed that after DBD intervention,the mRNA gene and protein expression of RELA,TNF,and IL-6 in the serum was significantly down-regulated.The mRNA expression of PI3K and AKT in the ileum and PI3K protein expression were also downregulated.In conclusion,DBD exerts its role in treating immunosuppressive diseases by regulating the PI3K-AKT signaling pathway.

关 键 词：当归补血汤 免疫抑制 网络药理学 

分 类 号：S853[农业科学—临床兽医学]