现代中西医结合杂志2025,Vol.34Issue(14):1918-1925,8.DOI:10.3969/j.issn.1008-8849.2025.14.004
基于网络药理学和实验验证探讨苦参碱干预强直性脊柱炎的分子机制
Molecular mechanisms of matrine in the treatment of ankylosing spondylitis based on network pharmacology and experimental validation
摘要
Abstract
Objective It is to identify the potential targets of action of matrine in the treatment of ankylosing spondylitis(AS)based on network pharmacology and experimental validation.Methods①A network pharmacology approach and mo-lecular docking were applied to predict potential targets and pathways of matrine in the treatment of AS.②15 patients with active AS treated in Guang'anmen Hospital of China Academy of Chinese Medical Science from September 2022 to June 2023 and 15 sex-and age-matched healthy volunteers undergoing physical examinations in the health examination center of this hospital during the same period were recruited,and the peripheral blood mononuclear cells(PBMC)of these subjects were extracted for in vitro experiment.5 groups were set up in this experiment:the PBMCs from healthy volunteers in the healthy group were taken and conventionally cultured;the PBMCs from active AS patients in the remaining 4 groups were taken and cultured,in which the AS group was conventionally cultured,while the low-,medium-,and high-dose groups of matrine were cultured with corresponding doses of matrine(final concentrations were 50,100,and 200 μg/mL,respective-ly).The protein expressions of Januskinase2(JAK2),signal transducer and activator of transcription 3(STAT3),p-JAK2,p-STAT3 and specific transcription factor retinoic acid receptor-related orphan receptor c(RORc)in the PBMCs were detected by Western blot method,the RORc mRNA expression in the PBMCs was detected by Real-time PCR.Re-sults ①JAK2,cathepsin K(CTSK),Januskinase3(JAK3)and Cytochrome P-450 19A1(CYP19A1)may be the poten-tial targets of matrine in regulating AS.②Compared with the healthy group,the relative protein expressions of p-JAK2,p-STAT3 and RORc,as well as the relative expression of RORc mRNA in PBMCs of the AS group were significantly in-creased(all P<0.05).Compared with the AS group,the relative protein expression of p-JAK2 in PBMCs of the low-and medium-dose groups of matrine,the relative protein expression of p-STAT3 in PBMCs of the medium-and high-dose groups of matrine,and the relative protein and mRNA expressions of RORc in PBMCs of all dose groups of in matrine were signifi-cantly reduced(all P<0.05).Conclusion Matrine may exert anti-AS effects through key targets such as JAK2,CTSK,JAK3,CYP19A1 and JAK2/STAT3 signaling pathway.关键词
强直性脊柱炎/苦参碱/网络药理学/分子对接/实验验证/酪氨酸激酶2/信号转导和转录活化因子3/特异性转录因子维甲酸相关孤儿核受体cKey words
ankylosing spondylitis/matrine/network pharmacology/molecular docking/experimental verification/JAK2/STAT3/RORc分类
医药卫生引用本文复制引用
屈馨宁,刘宏潇,宋俊垚,陈悦宁..基于网络药理学和实验验证探讨苦参碱干预强直性脊柱炎的分子机制[J].现代中西医结合杂志,2025,34(14):1918-1925,8.基金项目
中央高水平中医医院临床研究和成果转化能力提升项目(HLCMHPP2023049) (HLCMHPP2023049)
北京市中医药科技发展资金重点项目(BJZYZD-2023-02) (BJZYZD-2023-02)
中国中医科学院科技创新工程重大攻关项目(CI2021A01506) (CI2021A01506)
中国中医科学院科技创新工程重点协同攻关项目(2023 CI2023C072YLL) (2023 CI2023C072YLL)