桂林西瓜霜治疗口腔溃疡的潜在作用机制与药效物质基础研究  

Potential mechanism and pharmacodyamic substance of Guilin Xiguashuang for the treatment of oral ulcer

作　　者：张嘉宁 任越 王梓安 李莹莹 李纯 常华 张燕玲[1] ZHANG Jia-ning;REN Yue;WANG Zi-an;LI Ying-ying;LI Chun;CHANG Hua;ZHANG Yanling(Key Laboratory of TCM-information Engineering of State Administration of Traditional Chinese Medicine,School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488;Guangxi Research Center for Traditional Chinese Medicine,Guilin Guangxi 541004)

机构地区：[1]北京中医药大学,中药学院,国家中医药管理局中药信息工程重点实验室,中药制药与新药开发关键技术教育部工程研究中心,北京102488 [2]广西中药新药研发中心,广西桂林541004

出　　处：《中南药学》2023年第6期1429-1435,共7页Central South Pharmacy

基　　金：国家自然科学基金项目(No.82073996);桂林西瓜霜制剂作用机制解析研究(No.BUCM-2021-JS-FW-017)。

摘　　要：目的基于网络药理学、分子对接以及体外实验探讨桂林西瓜霜治疗口腔溃疡的潜在作用机制及物质基础。方法收集桂林西瓜霜的成分及靶标,与口腔溃疡的疾病靶标取交集,并进行拓扑及KEGG分析。选择关键靶标与活性成分进行分子对接以发现桂林西瓜霜治疗口腔溃疡的潜在物质基础。体外实验基于一氧化氮(NO)释放量、中性红吞噬作用、免疫荧光实验验证桂林西瓜霜的抗炎以及免疫调节作用,并进一步对关键靶标及物质基础进行验证。结果共获得交集靶标126个。KEGG结果表明桂林西瓜霜治疗口腔溃疡的机制与抗炎、调节免疫等相关,其中,C型凝集素受体、PI3K-Akt等信号通路可能为主要作用途径,原癌基因酪氨酸蛋白激酶(SRC)、肿瘤坏死因子(TNF)、血管内皮生长因子A(VEGFA)等可能是关键靶标。分子对接结果发现桂林西瓜霜中的射干、大黄等中药所包含的木犀草素、谷甾醇等活性成分可能为治疗口腔溃疡的潜在物质基础。体外实验验证结果发现桂林西瓜霜可促进RAW264.7细胞释放NO,同时抑制LPS诱导的RAW264.7细胞释放NO;增强RAW264.7细胞吞噬能力,促进RAW264.7细胞向M1型极化,并可调节SRC、TNF、VEGFA mRNA的表达量。药效实验结果显示射干、大黄等中药可能通过改变正常以及脂多糖诱导条件下RAW264.7细胞NO的释放量以发挥抗炎及免疫调节的作用。结论桂林西瓜霜通过多成分、多靶点、多通路协同作用抑制口腔溃疡的发生发展,可为今后临床进一步探讨桂林西瓜霜治疗口腔溃疡的机制及物质基础提供理论依据,并指导其二次开发。Objective To determine the potential mechanism and pharmacodyamic substance of Guilin Xiguashuang against oral ulcer based on network pharmacology,molecular docking,and in vitro experiments.Methods The components and potential targets of Guilin Xiguashuang were collected,and their intersections with disease targets of oral ulcer were analyzed by topology and KEGG.The key targets were selected for molecular docking with active components to determine the potential pharmacodyamic substance.Finally,the anti-inflammatory and immunomodulatory effects of Guilin Xiguashuang were verified based on nitric oxide(NO)release,neutral red phagocytosis and immunofluorescence,and the key targets and pharmacodyamic substance were further verified.Results Totally 126 targets were obtained by mapping the drug targets and disease targets.The mechanism of Guilin Xiguashuang for oral ulcer was related to the anti-inflammatory and immunomodulatory effects.Among them,C-type lectin,PI3K-Akt and other signaling pathways might be the main pathways;proto-oncogene tyrosine-protein kinase Src(SRC),tumor necrosis factor(TNF),and vascular endothelial growth factor A(VEGFA)might be the key targets.Luteolin,sitosterol and other active components in traditional Chinese medicine such as belamcandae rhizoma and rhei radix et rhizoma might be the potential effective pharmacodyamic substances for oral ulcer.In vitro validation showed that Guilin Xiguashuang promoted NO release from RAW264.7 cells and inhibited NO release from lipopolysaccharide-induced RAW264.7 cells.It also enhanced the phagocytic ability,promoted the polarization of RAW264.7 cells to M1 type,and regulated the expression of SRC,TNF and VEGFA mRNA.The pharmacodynamic results showed that belamcandae rhizoma and rhei radix et rhizoma may exert anti-inflammatory and immunomodulatory effects by changing the release of NO from RAW264.7 cells under normal and lipopolysaccharide conditions.Conclusion Guilin Xiguashuang can inhibit the occurrence and development of oral ulcer through the syne

关 键 词：桂林西瓜霜 口腔溃疡 作用机制 物质基础 

分 类 号：R285[医药卫生—中药学]