整合网络药理学、分子对接和细胞生物学探究白芨对坏死性小肠结肠炎的疗效及作用机制  

Integrating network pharmacology,molecular docking and cell biology to explore the efficacy and mechanism of Bletilla striata on necrotizing enterocolitis

作　　者：蒙玫君 陈浩[1,2] 沙卫红[1,2] MENG Meijun;CHEN Hao;SHA Weihong(Guangdong Cardiovascular Institute,Guangdong Provincial People′s Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080;Department of Gastroenterology,Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,China)

机构地区：[1]广东省心血管病研究所,广东省人民医院,广东省医学科学院,广东广州510080 [2]南方医科大学附属广东省人民医院(广东省医学科学院)消化内科

出　　处：《胃肠病学和肝病学杂志》2025年第4期521-528,共8页Chinese Journal of Gastroenterology and Hepatology

基　　金：国家自然科学基金(82170561);广东省自然科学基金(2022A1515012081);广东省高水平医院建设“登峰计划”重点基金(DFJH201803)。

摘　　要：目的运用网络药理学和细胞生物学验证探讨白芨治疗坏死性小肠结肠炎(necrotizing enterocolitis,NEC)的分子作用机制。方法通过中药系统药理学数据库(Traditional Chinese Medicine Systems Pharmacology Database,TCMSP)筛选出白芨有效成分;利用GeneCards、OMIM、PharmGKB和DisGeNet数据库筛选NEC的相关靶点,并与白芨活性成分作用靶点取交集;应用String数据库绘制PPI网络;通过Cytoscape软件绘制白芨-成分-靶点-疾病网络;借助DAVID数据库和R软件对靶点进行GO富集分析和KEGG通路富集分析;细胞生物学验证分析白芨多糖(Bletilla striata polysaccharide,BSP)对NEC的保护作用。结果共筛选得到白芨14个有效成分,涉及61个作用靶点,主要涉及炎症反应、氧化应激反应、细胞凋亡等,主要调节TNF、HIF-1、MAPK、NF-κB等信号通路,其作用机制包含抗氧化、抗炎、抑制细胞凋亡等。细胞生物学验证分析表明,BSP能够降低LPS引起的细胞凋亡,提高超氧化物歧化酶(superoxide dismutase,SOD)活性(P<0.01)并降低肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平(P<0.05)。结论白芨可能是通过多成分、多靶点、多通路等途径发挥其治疗NEC的作用,白芨中的活性成分BSP可能是其治疗NEC的物质基础。体外水平验证了BSP能够降低LPS引起的细胞损伤,降低氧化应激反应,提高抗氧化性,为白芨治疗NEC提供新思路。Objective To investigate the molecular mechanisms of Bletilla striata in treating necrotizing enterocolitis(NEC)using network pharmacology and cellular biology validation.Methods Effective components of Bletilla striata were screened using the Traditional Chinese Medicine Systems Pharmacology Database(TCMSP).Relevant targets for NEC were identified using GeneCards,OMIM,PharmGKB,and DisGeNet databases,and the obtained targets were intersected with the active ingredients of Bletilla striata.A protein-protein interaction(PPI)network was constructed using the STRING database.Bletilla striata-component-target-disease network was mapped using Cytoscape software.GO and KEGG pathway analyses for the targets were performed using the DAVID database and R software.The protective effects of Bletilla striata polysaccharide(BSP)on NEC were validated through cellular biology analysis.Results A total of 14 effective components of Bletilla striata were identified,involving 61 action targets,primarily associated with biological processes such as inflammatory responses,oxidative stress,and apoptosis.These components mainly modulate signaling pathways including TNF,HIF-1,MAPK,and NF-κB,with mechanisms of action including antioxidant,anti-inflammatory,and anti-apoptotic effects.Cellular biology validation analysis demonstrated that BSP could reduce cell apoptosis induced by lipopolysaccharide(LPS),enhance superoxide dismutase(SOD)activity(P<0.01),and decrease levels of tumor necrosis factor-α(TNF-α)(P<0.05).Conclusion Bletilla striata may exert its therapeutic effects through multiple components,targets,and pathways in treating NEC.The active component BSP in Bletilla striata may serve as the material basis for its treatment of NEC.In vitro validation confirmed that BSP could reduce cell damage induced by LPS,decrease oxidative stress responses,and enhance antioxidant properties,providing new insights into the treatment of necrotizing enterocolitis with Bletilla striata.

关 键 词：白芨 白芨多糖 坏死性小肠结肠炎 网络药理学 细胞生物学 

分 类 号：R574[医药卫生—消化系统]