SCM-198 Inhibits EMS Development by Reversing Decreased Proportions of IFN-γ+T Cells and CCR5+T Cells

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SCM-198 suppresses endometriotic growth in mice by increasing IFN-γ+ and CCR5+ T cells, likely through CCL5 upregulation.

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This paper studied the synthetic leonurine derivative SCM-198 in an endometriosis (EMS) mouse model, using RNA-seq enrichment analyses, flow cytometry, western blot, and in vitro/in vivo experiments to investigate mechanism. The authors found that SCM-198 significantly suppressed endometriotic lesion growth and affected pathways related to T cell differentiation/activation, cytokine production, and chemotaxis/migration, while also reversing decreased proportions of IFN-γ+ T cells and CCR5+ T cells in ectopic lesions. RNA-seq indicated increased CCL5 expression in ectopic lesions, and western blot was used to verify this, with the paper proposing that changes in CCR5+ T cells were likely linked to reduced CCL5 expression. A key limitation explicitly implied by the abstract is that the mechanistic basis was still being inferred from these molecular and immune-cell readouts rather than fully resolved. This paper is centrally about endometriosis — SCM-198 inhibition of EMS development via reversal of altered IFN-γ+ and CCR5+ T cell proportions.

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Abstract

Endometriosis is a common gynecological disease that causes severe pain and infertility. However, the available treatments for EMS are limited. SCM-198, a synthetic form of leonurine, possesses various abilities, including anti-inflammatory, immunomodulatory, antioxidant, anti-fibrotic, and anti-proliferative effects. Previous studies have shown that SCM-198 can inhibit the growth of ectopic lesions, but the specific mechanism remains unknown. The results of our studies indicate that SCM-198 significantly suppresses the endometriotic growth of EMS mice. Enrichment analysis of RNA-seq indicates that SCM-198 is involved in T cell differentiation, activation, cytokine production, stimulation of chemotaxis, and migration. Flow cytometry reveals that SCM-198 reverses the decreased proportions of IFN-γ + T cells and CCR5 + T cells in ectopic lesions. RNA-seq analysis shows that SCM-198 enhances the expression of CCL5 in the ectopic lesions, and western blot is conducted to verify this conclusion both in vivo and in vitro. These findings demonstrate that SCM-198 reverses the decreased proportions of IFN-γ + T cells and CCR5 + T cells, alleviating the growth of mouse ectopic lesions, and the changes in CCR5 + T cells are likely due to the reduced expression of CCL5.
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Abstract

Endometriosis is a common gynecological disease that causes severe pain and infertility. However, the available treatments for EMS are limited. SCM-198, a synthetic form of leonurine, possesses various abilities, including anti-inflammatory, immunomodulatory, antioxidant, anti-fibrotic, and anti-proliferative effects. Previous studies have shown that SCM-198 can inhibit the growth of ectopic lesions, but the specific mechanism remains unknown. The results of our studies indicate that SCM-198 significantly suppresses the endometriotic growth of EMS mice. Enrichment analysis of RNA-seq indicates that SCM-198 is involved in T cell differentiation, activation, cytokine production, stimulation of chemotaxis, and migration. Flow cytometry reveals that SCM-198 reverses the decreased proportions of IFN-γ + T cells and CCR5 + T cells in ectopic lesions. RNA-seq analysis shows that SCM-198 enhances the expression of CCL5 in the ectopic lesions, and western blot is conducted to verify this conclusion both in vivo and in vitro. These findings demonstrate that SCM-198 reverses the decreased proportions of IFN-γ + T cells and CCR5 + T cells, alleviating the growth of mouse ectopic lesions, and the changes in CCR5 + T cells are likely due to the reduced expression of CCL5. Similar content being viewed by others

References

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Maximal T cell-mediated antitumor responses rely upon CCR5 expression in both CD4(+) and CD8(+) T cells. Cancer Res. 2011;71(16):5455–66. Funding This work was supported by grants from the National Key R&D Program of China (2021YFE0206500 to M.D.), National Natural Science Foundation of China (82271713, 81630036, and 31970859 to M.D.), and the Research Program of Shanghai 4th People’s Hospital (sykyqd09001). Author information Authors and Affiliations Corresponding authors Ethics declarations Ethical Approval Our study was approved by the Research Ethics Committee of the Obstetrics and Gynecology Hospital of Fudan University, and all experiments were performed per the relevant guidelines and regulations (No. Kyy2023-41) (Shanghai, China). 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. 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 Lu, Y., Li, Y., Li, Y. et al. SCM-198 Inhibits EMS Development by Reversing Decreased Proportions of IFN-γ+T Cells and CCR5+T Cells. Reprod. Sci. 32, 2180–2189 (2025). https://doi.org/10.1007/s43032-025-01823-9 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-025-01823-9

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Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma Interferon-gamma

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