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16-01-2024 | Rheumatoid Arthritis | Original Article

The therapeutic effect of Loranthus parasiticus lignan derivatives on collagen-induced arthritis in rats through the SHBG/NFκB pathway

Authors: Jiali Bai, Cong Zhang, Yulin Liu, Nanzhen Kuang, Liangquan Xu, Zhengang Xu, Haiwei Wang, Renping Liu

Published in: Inflammopharmacology | Issue 1/2024

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Abstract

Lignan-rich beans, nuts, and various seeds are the main foods with antioxidative and hormone-modulating activities. Although the role of lignans in mediating hormone-dependent cancers and cardiovascular diseases is well characterized, the function of lignans in anti-arthritic activity and its underlying mechanisms remain unknown. Three new lignan derivatives, (-)-nortrachelogenin, trachelogenin, and matairesinol, were extracted from Loranthus parasiticus. After establishing the collagen-induced arthritis (CIA) model by intradermal injection of collagen, rats were treated with three new lignan derivatives ((-)-nortrachelogenin: 37%; trachelogenin: 27%; matairesinol: 25.7%) at a concentration of 50 mg/kg and 100 mg/kg, or methotrexate at 0.3 mg/kg. Mixed lignan derivatives significantly attenuated the immune responses in the joints of CIA rats, leading to lower levels of proinflammatory cytokines (IL-6 and TNF-α) and higher levels of free androgen in the serum compared to the CIA model. The results of molecular docking using AutoDock Vina showed that the lignan derivative (-)-nortrachelogenin was the most effective compound for binding to sex hormone-binding globulin (SHBG), thus inhibiting the activity of NFκB in LPS-stimulated macrophages. In this study, (-)-nortrachelogenin was identified as a novel natural lignan derivative with previously unrecognized anti-inflammatory activity. Its molecular mechanism appears related to the regulation of the NFκB/SHBG pathway. Our findings suggest that further application of sex hormone-like compounds in the treatment of rheumatoid arthritis and the potential clinical applications of (-)-nortrachelogenin are promising.
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Metadata
Title
The therapeutic effect of Loranthus parasiticus lignan derivatives on collagen-induced arthritis in rats through the SHBG/NFκB pathway
Authors
Jiali Bai
Cong Zhang
Yulin Liu
Nanzhen Kuang
Liangquan Xu
Zhengang Xu
Haiwei Wang
Renping Liu
Publication date
16-01-2024
Publisher
Springer International Publishing
Published in
Inflammopharmacology / Issue 1/2024
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-023-01409-4

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