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

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

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1104153

DOI=10.3389/fphar.2023.1104153

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterized by activated M1-like macrophage in the joint. <italic>Xanthium mongolicum</italic> Kitag (<italic>X. mongolicum</italic>) is a traditional medicinal plant that has long been used to treat RA and other immune diseases in China.</p><p><bold>Methods:</bold> Fractions of <italic>X. mongolicum</italic> were separated based on polarity. Anti-RA activity of the fractions were screened by LPS-stimulated RAW264.7 macrophage <italic>in vitro</italic>. 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 <italic>in vivo</italic> and LPS-stimulated macrophage <italic>in vitro</italic>.</p><p><bold>Results:</bold> Sesquiterpene lactones-enriched fraction from <italic>X. mongolicum</italic> (SL-XM) exhibited the strongest anti-RA activity among all components <italic>in vitro</italic>. 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.</p><p><bold>Discussion:</bold> The main anti-RA active fraction of <italic>X. mongolicum</italic> may be the Sesquiterpene lactones, which includes five key compounds. SL-XM may exert its anti-RA effect by suppressing M1 macrophage polarization <italic>via</italic> the NF-κB and MAPK signaling pathway.</p>