摘要
目的通过网络药理学和实验验证探讨筒鞘蛇菰Balanophora involucrata Hook.f.对药源性肝损伤(DILI)的保护作用及其机制。方法文献检索筒鞘蛇菰的化学成分,用多重数据库分析预测筒鞘蛇菰的药理机制。用对乙酰氨基酚(APAP)诱导小鼠DILI模型,以联苯双酯为阳性药,通过组织病理检查、生化检测、免疫组化及分子生物学检查验证筒鞘蛇菰提取物蛇菰多糖(BPS)对DILI的疗效及作用机制。结果筒鞘蛇菰调控DILI的主要活性成分为圣草酚、β-香树脂醇、β-谷甾醇等,核心靶点有TNF、MAPK3、PTGS2、BCL2L1等;GO功能富集分析显示:核心蛋白参与的生物过程涉及凋亡过程调节;KEGG富集分析显示:筒鞘蛇菰调节APAP肝损伤的通路主要涉及凋亡相关信号通路。BPS可显著降低DILI模型小鼠的肝指数及肝组织中转氨酶的含量,改善肝组织的病理状态和炎症浸润;同时,BPS可减轻模型小鼠肝细胞的凋亡程度,抑制凋亡蛋白caspase 3、C-caspase 3的激活,促凋蛋白Bax的表达,升高抑凋蛋白Bcl-2的表达。结论筒鞘蛇菰可能通过Bax/Bcl-2/caspase 3信号通路调控细胞凋亡对小鼠DILI起预防和治疗作用。
OBJECTIVE To study the protective effects and mechanisms of Balanophora involucrata Hook.f on drug-induced liver injury(DILI)by Network pharmacology and experimental validation.METHODS Through literature searches,the chemical composition of B.involucrata was compiled and the pharmacological mechanism was predicted using the diverse databases.DILI mice model was established by Acetaminophen(APAP),with Bifendate as a positive drug group.The study encompassed macroscopic specimens,histopathological examination,biochemical assays,immunohistochemistry,and molecular biology analyses to unravel the therapeutic effects and pharmacological mechanisms of polysaccharide of B.involucrata(BPS)on DILI.RESULTS The sanctuone,β-eudesmol,andβ-sitosterol as the principal active components of B.involucrata in regulating DILI.Core targets included TNF,MAPK3,PTGS2,BCL2L1.GO functional enrichment analysis implicated processes associated with apoptosis regulation.KEGG analysis highlighted the involvement of apoptosis-related signaling pathways.The liver index,ALT,and AST levels of DILI model mice were significantly reduced,and the liver tissue pathology and inflammatory infiltration were improved by BPS treated.Additionally,BPS mitigated hepatocyte apoptosis by inhibiting caspase 3 activation,suppressing Bax expression,and elevating Bcl-2 expression.CONCLUSION B.involucrata could prevent and treat APAP-induced liver injury by regulating cell apoptosis through the Bax/Bcl-2/caspase 3 signaling pathway.
作者
王超
蔡华俊
王晨晖
谭伟
吴昊
WANG Chao;CAI Huajun;WANG Chenhui;TAN WEI;WU Hao(Medical Department of Hubei Enshi University,Enshi,Hubei,445000 P.R.China;Research Institute of Anti Rheumatic Tujia Drugs,Hubei Enshi University,Enshi,Hubei,445000 P.R.China;Department of Gastroenterology,Chongqing People's Hospital,Chongqing,40000 P.R.China;Key Laboratory of Rheumatic Disease Occurrence and Intervention,Hubei University for Nationalities,Enshi,Hubei,445000 P.R.China)
出处
《华西药学杂志》
CAS
CSCD
北大核心
2024年第5期515-521,共7页
West China Journal of Pharmaceutical Sciences
基金
湖北省自然科学基金面上项目(2022CFB515)
恩施州科技局指导性项目(JCY2021000033)
湖北恩施学院指导性项目(KYJZ202314)。
