Oxymatrine attenuates chronic allograft rejection by modulating immune responses and inhibiting fibrosis.

Autor: Ren SH; Department of General Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China; Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China., Shao B; Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China., Wang HD; Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China., Zhang JY; Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China., Qin H; Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China., Sun CL; Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China., Zhu YL; Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China., Wang ZB; Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China., Lan X; Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China., Gao YC; Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China., Wang H; Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China; Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin, China. Electronic address: hwang1@tmu.edu.cn.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Dec 15; Vol. 985, pp. 177082. Date of Electronic Publication: 2024 Oct 30.
DOI: 10.1016/j.ejphar.2024.177082
Abstrakt: Background: Chronic rejection (CR) is a significant obstacle to long-term allograft survival. Oxymatrine (OMT) is a prominent bioactive compound widely utilized in traditional Chinese medicine for the management of inflammatory disorders and it has considerable potential as a therapeutic candidate for the treatment of CR.
Methods: Well-established major histocompatibility complex (MHC) class II mismatched B6 mice. C-H-2 bm12 -to-C57BL/6 mouse transplantation was used as a CR model. Hematoxylin and eosin (H&E) staining, immunohistochemistry, and Masson's trichrome staining were used to assess pathological changes in the grafts, and the percentages of immune cells were determined by flow cytometry. The effects of OMT on the regulation of CD4 + T cell differentiation and cytokine secretion were verified in vitro.
Results: OMT effectively alleviated pathological graft damage, characterized by chronic changes in intimal lesions, vasculopathy, and fibrosis and significantly prolonged cardiac allograft survival. OMT exerted its immunomodulatory effects by inhibiting T helper 1 (Th1) and T helper 17 (Th17) cell differentiation while promoting Treg differentiation both in vivo and in vitro. Further studies revealed that OMT inhibited the phosphorylation of mammalian target of rapamycin (mTOR), which is a potential mechanism underlying its immunosuppressive effects. OMT also inhibited the activation of B cells and the production of donor-specific antibody (DSA). In addition, OMT effectively alleviated chronic changes in fibrosis in cardiac allografts, and these changes may be related to the inhibition of the transforming growth factor-β (TGF-β)-Smad 2/3 pathway.
Conclusions: OMT attenuated CR by modulating the immune response and inhibiting graft fibrosis. Further in-depth investigations of OMT may provide valuable insights into the development of novel therapeutic strategies for CR inhibition.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Hao Wang reports was provided by National Natural Science Foundation of China. Hao Wang reports was provided by Natural Science Foundation of Tianjin. Hao Wang reports financial support was provided by Science and Technology Project of Tianjin Health Commission. Hao Wang reports financial support was provided by Tianjin Key Medical Discipline (Specialty) Construction Project. Xu Lan reports financial support was provided by National Natural Science Foundation of China. Yongchang Gao reports financial support was provided by Tianjin Municipal Science and Technology Bureau and the Tianjin Natural Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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