机构地区:[1]首都医科大学中医药学院,北京100069 [2]中医络病研究北京市重点实验室,北京100069 [3]中国中医科学院中药研究所,北京100700
出 处:《中国中药杂志》2024年第21期5865-5876,共12页China Journal of Chinese Materia Medica
基 金:国家重点研发计划项目(2023YFC3504003);国家自然科学基金面上项目(81473360)。
摘 要:基于液质联用技术快速辨识和定量吴茱萸汤(Wuzhuyu Decoction,WZYD)纳米相态(nanophase of WZYD,WZYD-N)和沉淀相态(suspension phase of WZYD,WZYD-S)成分组成,并结合初步药效实验以及网络药理学分析,探究WZYD 2种相态抗炎镇痛作用差异的物质基础。采用差速离心-透析法分离WZYD不同相态,通过粒度分析仪、透射电镜表征WZYD-N和WZYD-S的粒径、Zeta电位、PDI、形貌;利用UPLC-QQQ-MS/MS建立WZYD中23种代表性成分的含量测定方法,明确WZYD不同相态成分含量差异;建立醋酸诱发小鼠毛细血管通透性增强炎症模型和醋酸扭体疼痛模型初步研究WZYD不同相态抗炎镇痛作用;应用网络药理学筛选WZYD抗炎镇痛关键靶点与活性成分,结合液质定量结果,分析WZYD不同相态成分-药效关系。结果显示,分离得到的WZYD-N主要由200 nm左右的球形自组装聚集体组成,PDI约0.299,电位约-22.1 mV;以等生药量为单位,黄柏酮和二氢吴茱萸卡品碱在WZYD-N和WZYD-S中含量相当,吴茱萸次碱、吴茱萸卡品碱、吴茱萸苦素、柠檬苦素和人参皂苷Ro在WZYD-S中含量更高,吴茱萸碱、去氢吴茱萸碱、人参皂苷Re、6-姜酚、人参皂苷Rg_(1)等15种成分在WZYD-N中含量更高,6-去氢姜二酮在WZYD-N、WZYD-S中含量均很低。初步药效实验表明,WZYD-N可减少小鼠扭体次数,抑制醋酸引起的疼痛反应,表现出与WZYD近似的镇痛作用;WZYD-S可降低小鼠腹腔灌洗液吸光度,表现出与WZYD近似的抗炎作用。网络药理学分析去氢吴茱萸碱、吴茱萸次碱、6-姜酚、人参皂苷Rb_(1)等可能为WZYD镇痛活性成分,柠檬苦素、吴茱萸苦素、人参皂苷Ro等可能为WZYD抗炎活性成分,为WZYD药效物质发现与复方制剂研发提供新思路。This study rapidly identified and quantified the chemical components of the Wuzhuyu Decoction nanophase(WZYD-N)and suspension phase(WZYD-S)using ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry(UPLC-QQQ-MS/MS).Based on preliminary pharmacodynamic experiments and network pharmacology analysis,the differential anti-inflammatory and analgesic activities of WZYD-N and WZYD-S were explored to understand their pharmacodynamic basis.WZYD-N and WZYD-S were separated by differential centrifugation-dialysis,and their particle size,Zeta potential,PDI,and morphology were characterized by dynamic light scattering and transmission electron microscopy.A method was established to quantify 23 representative components of WZYD using UPLC-QQQ-MS/MS,clarifying the differences in component content between the two phases.The anti-inflammatory and analgesic activities of WZYD-N and WZYD-S were preliminarily investigated using the acetic acid-induced enhanced capillary permeability inflammation model and the acetic acid writhing pain model.Network pharmacology was applied to screen the key anti-inflammatory and analgesic targets and active components of WZYD,and the relationship between the components and pharmacodynamics of WZYD-N and WZYD-S was analyzed based on quantitative results.The results showed that WZYD-N primarily consisted of spherical self-assembled aggregates around 200 nm,with a PDI of approximately 0.299 and a zeta potential of-22.1 mV.With an equivalent amount of crude drugs,obacunone and dihydroevocarpine were quantified in equal amounts in WZYD-N and WZYD-S.The content of rutaecarpine,evocarpine,rutaevine,limonin,and ginsenoside Ro was higher in WZYD-S,while 15 other components,including evodiamine,dehydroevodiamine,ginsenoside Re,6-gingerol,and ginsenoside Rg_(1),were higher in WZYD-N.Moreover,6-dehydrogingerdione was low in both WZYD-N and WZYD-S.Preliminary pharmacodynamic experiments showed that WZYD-N could reduce the number of writhing responses and inhibit pain respo
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