Therapeutic effects of S-allyl-L-cysteine in a mouse endometriosis model and its immunomodulatory effects via regulation of T cell subsets and cytokine expression

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S-allyl-L-cysteine (SAC) treatment inhibited endometriotic lesion growth in mice by promoting apoptosis, reducing adhesion, and modulating T cell subsets and cytokine expression.

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The paper studies whether S-allyl-L-cysteine (SAC), an antioxidant constituent of aged garlic extracts, can treat endometriosis and modulate immune responses in a surgically induced mouse endometriosis model. Mice received oral SAC (30 mg/kg daily) for 28 days, and the authors assessed endometriotic lesion growth histologically, measured adhesion-, apoptosis-, and inflammation-related gene expression by PCR, and used spleen flow cytometry to examine T cell subset changes and cytokine production in spleen and lesions. SAC significantly inhibited lesion growth, promoted apoptosis- and reduced antiadhesion-related gene expression, and altered splenic CD4+ and CD8+ T cell subsets along with inflammatory cytokine production, with the main limitation being reliance on an induced mouse model and the study’s short intervention window. This paper is centrally about endometriosis — it evaluates SAC’s therapeutic and immunomodulatory effects in a mouse endometriosis model.

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Abstract

Background Endometriosis is a female hormone-dependent gynecological disorder characterized by chronic inflammation. Therefore, the development of novel treatment strategies that can diminish the side effects of the long-term use of hormone-based drugs has been emphasized. S-Allyl-L-cysteine (SAC) is the major constituent of aged garlic extracts. Although the therapeutic effects resulting from the antioxidant properties of SAC have been extensively studied in inflammatory diseases, the therapeutic efficacy of SAC in endometriosis has not been described. In this study, we investigated the therapeutic potential of SAC for endometriosis using a mouse model.

Methods

An endometriosis mouse model was surgically induced, and oral treatment with 30 mg/kg SAC was administered daily for 28 days. The development of endometriotic lesions was assessed by histological analysis, and the expression profiles of adhesion-, apoptosis-, and inflammation-related genes were evaluated by PCR. Flow cytometric analysis of mouse spleen was conducted to assess changes in lymphocyte subpopulations.

Results

SAC treatment significantly inhibited endometriotic lesion growth. Transcriptional expression analysis revealed the antiadhesion and apoptosis-promoting effects of SAC. In particular, SAC showed an effective immune modulatory response by altering splenic CD4+ and CD8+ T cell subsets and inflammatory cytokine production in the spleen and endometriotic lesions.

Conclusion

This study newly elucidates the inhibitory effects of SAC on the growth of endometriosis in a mouse model and describes its immunomodulatory effects. Similar content being viewed by others Data availability The datasets generated during the current study are available from the corresponding author upon reasonable request.

References

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Hexane extract of aged black garlic reduces cell proliferation and attenuates the expression of ICAM-1 and VCAM–1 in TNF-alpha-activated human endometrial stromal cells. Int J Mol Med. 2013;32:67–78. Funding This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI22C1424). This research was supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education (grant number: RS-2023-00246500). Author information Authors and Affiliations Contributions WP did an investigation, performed whole experiments and wrote the main manuscript text. GS prepared figures and wrote the main manuscript text. WL and SP supervised the direction of the paper, validated all the data and edited the manuscript. Corresponding author Ethics declarations Conflict of interest The authors declare that they have no conflict of interest. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Electronic supplementary material Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Park, W., Song, G., Lim, W. et al. Therapeutic effects of S-allyl-L-cysteine in a mouse endometriosis model and its immunomodulatory effects via regulation of T cell subsets and cytokine expression. Pharmacol. Rep 76, 1089–1099 (2024). https://doi.org/10.1007/s43440-024-00625-1 Received: Revised: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43440-024-00625-1

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Cysteine Cysteine Cysteine Cysteine Cysteine Cysteine Cysteine Cysteine Cysteine Cysteine Cysteine Cysteine Cysteine Cysteine Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines

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