基于网络药理学的香菊制剂治疗鼻炎、鼻窦炎的药效物质基础研究

Study on the pharmacodynamic material basis of Xiangju Preparations in the treatment of rhinitis and sinusitis based on network pharmacology

本研究拟通过构建“成分-靶点-通路”的多层次网络整合分析,探讨香菊制剂(香菊片、香菊滴剂)治疗鼻炎、鼻窦炎的药效物质及其作用机制。采用高效液相色谱-四级杆飞行时间质谱(HPLC-QTOF/MS)技术首次鉴定出香菊制剂中137种化学成分,对其中59种潜在活性成分进行网络药理学分析,结果表明咖啡酸、洋川芎内酯F、迷迭香酸、藁本内酯、升麻素苷、蒙花苷、木兰脂素、木犀草素、洋川芎内酯I及没食子酸等10种成分可作用于肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素1B(interleukin 1B,IL1B)、蛋白激酶B(protein kinase B,AKT1)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、信号传导及转录激活蛋白-3(signal transducer and activator of transcription 3,STAT3)等核心靶点,通过调节晚期糖基化产物-晚期糖基化终末产物受体(advanced glycosylation end products-receptor of AGEs,AGE-RAGE)、TNF、核转录因子κB(nuclear factor kappa B,NF-κB)、环磷酸鸟苷-蛋白激酶G(cyclic guanosine monophosphate-protein kinase G,cGMP-PKG)等信号通路进而治疗鼻炎、鼻窦炎。分子对接结果显示,以上10种化学成分与5个关键靶点间均具有良好的结合性能,说明这10种化学成分为香菊制剂潜在药效物质。综上,本研究初步阐明了香菊制剂治疗鼻炎、鼻窦炎的药效物质及其作用机制,为香菊制剂的临床应用提供了理论基础。

In order to clarify the pharmacodynamic substances and mechanism of Xiangju Preparations(Xiangju Tablets,Xiangju Drops)in the treatment of rhinitis and sinusitis,the multi-level network integration analysis of"ingredients-targets-pathways"was conducted.137 chemical constituents were identified in Xiangju Preparations by high pressure liquid chromatography-quadrupole-time of flight mass spectrometry(HPLC-QTOF/MS)for the first time.Network pharmacology analysis was performed on 59 potential active components.The results of network pharmacology analysis demonstrated that the medicinal ingredients in Xiangju Preparations included caffeic acid,senkyunolide F,rosmarinic acid,ligustilide,prim-O-glucosylcimifugin,linarin,magnolin,luteolin,senkyunolide I and gallic acid.These ingredients act on the crucial targets of tumor necrosis factor(TNF),interleukin 1B(IL1B),protein kinase B(AKT1),vascular endothelial growth factor A(VEGFA),signal transducer and activator of transcription 3(STAT3)and participate in the regulation of advanced glycosylation end productsreceptor of AGEs(AGE-RAGE),TNF,nuclear factor kappa B(NF-κB),and cyclic guanosine monophosphateprotein kinase G(cGMP-PKG)signaling pathways to effectively treat rhinitis and sinusitis.The excellent binding performance between above 10 active components and 5 key target proteins was further confirmed by molecular docking,indicating that these 10 ingredients are pharmacodynamic substances of Xiangju preparations.In conclusion,this study preliminarily clarified the effective components and mechanism of Xiangju preparations in the treatment of rhinitis and sinusitis,and provided a theoretical basis for the clinical application of Xiangju preparations.