文献类型：期刊文献

中文题名：基于血清药物化学与代谢组学研究DEPLJ抗类风湿关节炎的作用机制

英文题名：Study on mechanism of DEPLJ in treating rheumatoid arthritis based on serum pharmacology and metabolomics

作者：赵敏[1];强宇靖[1];马佳荣[1];王玉辉[1];李莉[1];苗小楼[2];姚世霞[3];李芸[1]

第一作者：赵敏

机构：[1]甘肃中医药大学药学院,甘肃兰州730000;[2]中国农业科学院兰州畜牧与兽药研究所,甘肃兰州730050;[3]甘肃省药品检验研究院,甘肃兰州730070

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

年份：2026

卷号：42

期号：4

起止页码：756

中文期刊名：中国药理学通报

外文期刊名：Chinese Pharmacological Bulletin

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金资助项目(No 82360773)。

语种：中文

中文关键词：甘草汁蒸制高乌头;类风湿关节炎;血清药化;代谢组学;炎症;NF-κB轴

外文关键词：Aconitum sinomontanum Nakai steamed with licorice juice;rheumatoid arthritis;serum pharmacochemistry;metabolomics;inflammation;NF-κB axis

摘要：目的联合血清药物化学-非靶向代谢组学-药效学,阐明甘草汁蒸制高乌头“减毒存效”部位(DEPLJ)对风寒湿痹类风湿关节炎(RA)的疗效及机制。方法制备DEPLJ,采用Ⅱ型胶原+弗氏完全佐剂联合风寒湿条件建立RA病证大鼠模型,设空白组、模型组、雷公藤多苷片组及DEPLJ高、中、低剂量组。观测各组大鼠一般状态和足趾肿胀度;HE、番红固绿和TRAP染色观察踝关节病理变化;UHPLC-QE-MS对DEPLJ原药成分、入血成分及入血代谢成分和滑膜组织非靶代谢组学分析;ELISA实验检测RF、CRP、IL-6、CCP、TNF-α水平;IF、Western blot和qPCR实验检测各组大鼠踝关节中NF-κB、VEGF、MMP-3、TIMP-1表达。结果DEPLJ明显改善模型大鼠滑膜增生、软骨破坏及破骨细胞活化,降低RF、CRP、CCP、IL-6、TNF-α水平。血清药物化学鉴定出2185个入血成分,以高乌甲素、脱氧乌头碱等为代表。代谢组学发现DEPLJ回调69种差异代谢物,主要涉及VEGF信号通路及胆固醇-胆汁酸轴,提示通过胆汁酸-NF-κB轴调控代谢重编程。分子实验证实DEPLJ抑制踝关节NF-κB、VEGF、MMP-3表达,上调TIMP-1。结论DEPLJ以高乌甲素等关键生物碱为核心,经多组分-多通路协同调控“代谢-免疫”网络,明显改善风寒湿痹RA病症。
Aim To elucidate the therapeutic efficacy,material basis,and molecular mechanism of the detoxifying and efficacy-enhancing part of Aconitum sinomontanum Nakai steamed with licorice juice(DEPLJ)against rheumatoid arthritis(RA)with windcold-dampness bi syndrome through integrated serum pharmacochemistry,untargeted metabolomics,and pharmacodynamics analysis.Methods DEPLJ was prepared.RA disease model was induced in rats with type II collagen+complete Freund's adjuvant,combined with wind-cold-damp environmental stimuli to establish the RA disease-syndrome model.Rats were randomly divided into the blank,model,Tripterygium glycosides tablet,and high-,medium-,low-dose DEPLJ groups.General condition and paw swelling were observed;ankle joint pathology was examined by HE,Safranin O-Fast Green,and TRAP staining.UHPLC-QE-MS was employed to analyze DEPLJ constituents,blood-absorbed components,and their metabolites,as well as for synovial tissue untargeted metabolomics.ELISA was used to detect RF,CRP,CCP,IL-6,and TNF-αlevels.NF-κB,VEGF,MMP3,and TIMP-1 expression in ankle joints was determined by immunofluorescence,Western blot,and qPCR.Results DEPLJ significantly ameliorated synovial hyperplasia,cartilage destruction,and osteoclast activation,while reducing serum RF,CRP,CCP,IL-6,and TNF-αlevels.Serum pharmacochem istry identified 2185 blood-absorbed constituents,predominantly lappaconitine,deoxyaconitine,cinnamaldehyde,and glycyrrhetinic acid.Metabolomics revealed that DEPLJ reversed 69 differential metabolites,primarily involving VEGF signaling,cholesterolbile acid axis,glycerophospholipid,histidine,taurine,pantothenate,and pyrimidine metabolism,suggesting modulation of metabolic reprogramming via the bile acid-NF-κB axis to reverse metabolic-immune dysregulation.Molecular experiments confirmed that DEPLJ suppressed NF-κB,VEGF,and MMP-3 expression while upregulating TIMP-1 in ankle joints.Conclusions DEPLJ,with key alkaloids such as lappaconitine as core components,synergistically regulates the metabolic-immune network through multicomponent and multi-pathway mechanisms,significantly improving RA with wind-cold-dampness bi syndrome,providing a foundation for target validation and novel drug development.