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

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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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Funding

This work was supported by the Outstanding Youth Fund Project in Jiangxi Province (No. 2018ACB21044), the National Natural Science Foundation of Jiangxi Province (No. 20192BAB205121), and the National Natural Science Foundation of China (NSFC) (No. 32360183).

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Authors and Affiliations

  1. Clinical Pharmacy, Changzhi Maternal and Child Health Care Hospital, Changzhi, 046011, China

    Jiali Bai

  2. Department of Immunology, Medical College of Nanchang University, Nanchang, 330031, China

    Cong Zhang, Yulin Liu, Nanzhen Kuang, Liangquan Xu, Zhengang Xu & Renping Liu

  3. Obstetrics Department, Changzhi Maternal and Child Health Care Hospital, Changzhi, 046011, China

    Haiwei Wang

Authors
  1. Jiali Bai
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  2. Cong Zhang
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  3. Yulin Liu
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  4. Nanzhen Kuang
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  5. Liangquan Xu
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  6. Zhengang Xu
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  7. Haiwei Wang
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  8. Renping Liu
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Contributions

All the authors contributed to the conception and design of the study. B and L performed material preparation, data collection, and analyses. The first draft of the manuscript was written by L and Z, and all the authors commented on the previous versions of the manuscript. All authors have reviewed and approved the final manuscript.

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Correspondence to Renping Liu.

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Bai, J., Zhang, C., Liu, Y. et al. The therapeutic effect of Loranthus parasiticus lignan derivatives on collagen-induced arthritis in rats through the SHBG/NFκB pathway. Inflammopharmacol 32, 873–883 (2024). https://doi.org/10.1007/s10787-023-01409-4

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  • DOI: https://doi.org/10.1007/s10787-023-01409-4

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