Sesquiterpene lactones-enriched fractions from Xanthium mongolicum Kitag alleviate RA by regulating M1 macrophage polarization via NF-κB and MAPK signaling pathway

Jing Han; Jingwen Wang; Yicun Wang; Zhiqi Zhu; Siwang Zhang; Bingrong Wu; Mingsong Meng; Jianning Zhao; Dongsheng Wang

doi:10.3389/fphar.2023.1104153

Sesquiterpene lactones-enriched fractions from Xanthium mongolicum Kitag alleviate RA by regulating M1 macrophage polarization via NF-κB and MAPK signaling pathway

Front Pharmacol. 2023 Jan 26:14:1104153. doi: 10.3389/fphar.2023.1104153. eCollection 2023.

Authors

Jing Han¹, Jingwen Wang², Yicun Wang³, Zhiqi Zhu¹, Siwang Zhang¹, Bingrong Wu¹, Mingsong Meng¹, Jianning Zhao³, Dongsheng Wang³

Affiliations

¹ School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
² Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.
³ Department of Orthopedics, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.

Abstract

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterized by activated M1-like macrophage in the joint. Xanthium mongolicum Kitag (X. mongolicum) is a traditional medicinal plant that has long been used to treat RA and other immune diseases in China. Methods: Fractions of X. mongolicum were separated based on polarity. Anti-RA activity of the fractions were screened by LPS-stimulated RAW264.7 macrophage in vitro. The major active compounds were identified by UPLC-MS and quantified by HPLC. The anti-RA effects of the active fraction was evaluated in complete freund's adjuvant (CFA)-induced arthritis and collagen-induced arthritis (CIA) mouse models in vivo and LPS-stimulated macrophage in vitro. Results: Sesquiterpene lactones-enriched fraction from X. mongolicum (SL-XM) exhibited the strongest anti-RA activity among all components in vitro. Five major constituents i.e., Xanthinosin (1), Xanthatin (2), Mogolide D (3), Mogolide E (4), and Mogolide A (5) were identified as major compounds of SL-XM. SL-XM ameliorated symptoms of CFA and CIA induced arthritis mice model. Furthermore, SL-XM treatment inhibited LPS-induced M1 macrophages polarization. In addition, SL-XM inhibited the phosphorylation of NF-κB and MAPK signaling pathways in LPS-induced macrophage and CIA-challenged mice. Discussion: The main anti-RA active fraction of X. mongolicum may be the Sesquiterpene lactones, which includes five key compounds. SL-XM may exert its anti-RA effect by suppressing M1 macrophage polarization via the NF-κB and MAPK signaling pathway.

Keywords: Xanthium mongolicum kitag; macrophage; rheumatoid arthritis; sesquiterpene lactone; traditional Chinese medicine.

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 31900283 to JH); the Natural Science Foundation of Nanjing University of Chinese Medicine (No. NZY31900283 to JH); the China Postdoctoral Science Foundation (2021T140786 to DW); the Nanjing Postdoctoral Science Foundation (48289 to DW); Natural Science Foundation of Jiangsu province (No. BK20221556 to DW); the Jinling Hospital Postdoctoral Science Foundation (48289 to DW); and the Jinling Hospital Science Foundation (YYQN2021075 to DW).