摘要
目的探究小柴胡颗粒发挥退热作用的分子机制。方法基于指纹图谱与超高效液相色谱-质谱(UHPLC-MS)技术分离鉴定小柴胡颗粒化学成分;应用PubChem、Swiss和chEMBL数据库获取成分靶点并对其进行分类;利用GeneCard、DisGeNET数据库获取发热症状靶点;将药物靶点与发热靶点取交集,构建小柴胡颗粒退热靶点库,并筛选其中的核心靶点;构建干酵母致热大鼠模型,监测大鼠24 h内体温并检测血清中细胞因子含量。结果得到小柴胡颗粒化学成分66个,退热潜在靶点68个,分类数量最多的类别为酶类,包括激酶、蛋白酶、氧化还原酶、磷酸酶等;小柴胡颗粒可显著降低干酵母致热大鼠在造模后4~24 h的体温,且中高剂量与阿司匹林作用相当;可显著降低肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)、干扰素γ(IFN-γ)、白细胞介素-1β(IL^(-1)β)和环氧合酶2(PTGS2)含量,对核因子κB(NF-κB)和激活蛋白1(AP-1)水平亦有一定的降低作用。结论小柴胡颗粒对酵母致热大鼠上升期、高峰期和下降期的体温均有显著降低作用,退热机制关联机体发热的多个环节,可能与降低机体炎症水平、抑制内生致热原和发热介质前列腺素E2(PGE2)合成的主要限速酶环氧合酶2有关。
Objective To explore the molecular mechanism of antipyretic effect of Xiaochaihu Granules(XCHG).Methods The chemical components of XCHG were separated and identified by fingerprint and UHPLC-MS technology.The targets of components were obtained and classified using PubChem,Swiss and chEMBL databases.The targets of fever were obtained from GeneCard and DisGeNET database.The drug targets and fever targets were intersected,the antipyretic targets database of XCHG was structured and the functional enrichment was analyzed.The model of rats induced by dried yeast was established,and the temperature of rats was monitored within 24 hours and the content of cytokines in serum was detected.Results 66 chemical components and 68 potential antipyretic targets of XCHG was screened out.Enzymes,including kinase,protease,oxidoreductase and phosphatase,were the most widely classified category.Compared with aspirin,XCHG could significantly reduce the body temperature of rats with fever at 4~24 hours after modeling,and the effect of medium dose and high dose were similar to that of aspirin.XCHG could significantly reduce the content of TNF-α,IL-6,IFN-γ,IL^(-1)βand PTGS2,also could decreased the lever of NF-κB and AP-1.Conclusion XCHG can significantly lower the body temperature of rats with fever induced by dried yeast in the rising,peak and falling periods.The antipyretic mechanism of XCHG is related to many links of fever,which may be related to reducing the level of inflammation,inhibiting endogenous pyrogen and PTGS2.
作者
马蓉
刘宏
郑如文
许招懂
江志强
张俊华
蒋研风羊
毕聪
MA Rong;LIU Hong;ZHENG Ruwen;XU Zhaodong;JIANG Zhiqiang;ZHANG Junhua;JIANG Yanfengyang;BI Cong(Guangzhou Baiyunshan Guanghua Pharmaceutical Co.,Ltd.,Guangzhou 510285,China)
出处
《药学研究》
CAS
2021年第8期497-503,共7页
Journal of Pharmaceutical Research
关键词
小柴胡颗粒
退热
分子机制
内生致热原
环氧合酶2
Xiaochaihu Granules(XCHG)
Antipyretic
Molecular mechanism
Endogenous pyrogen
Cyclooxygenase-2
作者简介
马蓉,女,高级工程师,研究方向:中药新药研发及产业化,E-mail:mr@bysgh.com;通信作者:毕聪,女,研究方向:中药网络药理学,Tel:020-84352958,E-mail:bicong812@126.com。
