Magnoflorine Ameliorates Collagen-Induced Arthritis by Suppressing the Inflammation Response via the NF-kappa B/MAPK Signaling Pathways

作者全名："Wang, Lei; Li, Pengfei; Zhou, Yu; Gu, Renjun; Lu, Ge; Zhang, Chunbing"

作者地址："[Wang, Lei; Zhou, Yu; Zhang, Chunbing] Nanjing Univ Chinese Med, Coll Clin Med 1, Nanjing 210023, Jiangsu, Peoples R China; [Li, Pengfei; Zhang, Chunbing] Nanjing Univ Chinese Med, Jiangsu Prov Hosp Chinese Med, Dept Clin Lab, Affiliated Hosp, Nanjing 210029, Jiangsu, Peoples R China; [Gu, Renjun] Nanjing Univ Chinese Med, Sch Chinese Med, Nanjing 210023, Jiangsu, Peoples R China; [Lu, Ge] Nanjing Univ Chinese Med, Coll Acupuncture Moxibust & Tuina, Nanjing 210023, Jiangsu, Peoples R China; [Zhang, Chunbing] Chongqing Med Univ, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China; [Zhang, Chunbing] Nanjing Univ Chinese Med, Jiangsu Prov Hosp Chinese Med, Dept Clin Lab, Affiliated Hosp, Nanjing 210029, Peoples R China"

通信作者："Zhang, CB (通讯作者)，Nanjing Univ Chinese Med, Jiangsu Prov Hosp Chinese Med, Dept Clin Lab, Affiliated Hosp, Nanjing 210029, Peoples R China."

来源：JOURNAL OF INFLAMMATION RESEARCH

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001002902800001

JCR分区：Q2

影响因子：4.2

年份：2023

卷号：16

期号：　

开始页：2271

结束页：2296

文献类型：Article

关键词：magnoflorine; rheumatoid arthritis; collagen-induced arthritis; macrophage; NF-kappa B/MAPK signaling

摘要："Objective: Magnoflorine (Mag) has been reported to have anxiolytics, anti-cancer, and anti-inflammatory properties. In this study, we aim to investigate the effects of Mag on the rheumatoid arthritis (RA) and explore the underlying mechanism using a collagen-induced arthritis (CIA) mouse model and a lipopolysaccharide (LPS)-stimulated macrophage inflammation model. Methods: The in vivo effects of Mag on CIA were studied by inducing CIA in a mouse model using DBA/1J mice followed by treatment with vehicle, methotrexate (MTX, 1 mg/kg/d), and Mag (5 mg/kg/d, 10 mg/kg/d, and 20 mg/kg/d), and the in vitro effects of Mag on macrophages were examined by stimulation of RAW264.7 cells line and peritoneal macrophages (PMs) by LPS in the presence of different concentrations of Mag. Network pharmacology and molecular docking was then performed to predict the the binding ability between Mag and its targets. Inflammatory mediators were assayed by quantitative real-time PCR and enzyme linked immunosorbent assay (ELISA). Signaling pathway changes were subsequently determined by Western blotting and immunohistochemistry (IHC). Results: In vivo experiments demonstrated that Mag decreased arthritis severity scores, joints destruction, and macrophages infiltration into the synovial tissues of the CIA mice. Network pharmacology analysis revealed that Mag interacted with TNF-alpha, IL-6, IL-1 beta, and MCP-1. Consistent with this, analysis of the serum, synovial tissue of the CIA mice, and the supernatant of the cultured RAW264.7 cells and PMs showed that Mag suppressed the expression of TNF-alpha, IL-6, IL-1 beta, MCP-1, iNOS, and IFN-beta. Furthermore, Mag attenuated the phosphorylation of p65, I kappa B alpha, ERK, JNK, and p38 MAPKs in the synovial tissues of the CIA mice and LPS-stimulated RAW 264.7 cells. Conclusion: Mag may exert anti-arthritic and anti-inflammatory effects by inhibiting the activation of NF-kappa B and MAPK signaling pathways."

基金机构："National Natural Science Foundation of China [11574156]; Foundation of State Key Laboratory of Ultrasound in Medicine and Engineering [2022KFKT021]; 333 Project of Jiangsu Province, China [BRA2018088]"

基金资助正文："Acknowledgments This work was supported by National Natural Science Foundation of China (Grant No. 11574156) ; and Foundation of State Key Laboratory of Ultrasound in Medicine and Engineering (Grant No. 2022KFKT021) ; and 333 Project of Jiangsu Province, China (Grant No. BRA2018088) ."