Carvacrol Shows Potential as a Treatment for Endometriosis with Inflammatory Reaction and Antioxidant Properties, Demonstrated in both In Vivo and In Vitro Studies

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Carvacrol treatment in mice reduced endometriosis lesion size and altered immune responses, while in vitro studies showed it regulated calcium, induced antioxidant effects, and modulated signaling pathways to activate autophagy.

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This paper investigated carvacrol’s potential as a treatment for endometriosis by examining its inflammatory regulation and antioxidant effects using both a mouse in vivo model and an in vitro human cell model of endometriosis. In C57BL/6J mice orally given 100 mg/kg carvacrol for 4 weeks, the authors reported decreased lesion size, increased T cell numbers in the spleen, and increased expression of cytokine-related genes in tissues; in immortalized human ovarian endometriotic stromal cells, carvacrol was reported to regulate calcium homeostasis, induce antioxidant effects, increase inflammatory response, deactivate the PI3K signaling pathway, and induce autophagy. A stated limitation is that in vitro experiments used an immortalized stromal line rather than primary tissues, and the study’s in vivo findings are based on a specific dosing regimen and endpoints. This paper is centrally about endometriosis — it tests carvacrol’s anti-inflammatory/antioxidant and autophagy/PI3K-related effects in models of endometriosis.

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Abstract

Carvacrol is a phenolic monoterpenoid found in essential oils of oregano, thyme, and other plants. It possesses pharmacological activities, including antioxidant, anticancer, and anti-inflammatory properties, against several diseases. However, research on the treatment effect of endometriosis has not yet been conducted. Endometriosis is a condition characterized by tissues resembling the endometrium beyond the confines of the uterus, leading to intense pelvic pain and heightened risks of infertility. This study aimed to confirm the effectiveness of carvacrol as a treatment strategy for endometriosis with inflammatory regulation and antioxidant property. In the in vivo study, C57BL/6 J mice were orally administered 100 mg/kg carvacrol for 4 weeks and confirmed a decreased size of endometriosis lesions in the carvacrol-treated group, increased number of T cells in the spleen, and increased expression of cytokine-related genes in both tissues. Immortalized human ovarian endometriotic stromal cells (ihOESCs), derived from endometriotic lesions in patients, were used as an in vitro model for studying endometriosis pathophysiology. The findings of the in vitro study confirmed that carvacrol regulates calcium homeostasis, induces antioxidant effects, increases inflammatory response, deactivates the phosphatidylinositol 3-kinase (PI3K) signaling pathway, and ultimately induces autophagy. Therefore, we determined that carvacrol is suitable as an anti-inflammatory and anti-oxidant treatment strategy for endometriosis.
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Abstract

Carvacrol is a phenolic monoterpenoid found in essential oils of oregano, thyme, and other plants. It possesses pharmacological activities, including antioxidant, anticancer, and anti-inflammatory properties, against several diseases. However, research on the treatment effect of endometriosis has not yet been conducted. Endometriosis is a condition characterized by tissues resembling the endometrium beyond the confines of the uterus, leading to intense pelvic pain and heightened risks of infertility. This study aimed to confirm the effectiveness of carvacrol as a treatment strategy for endometriosis with inflammatory regulation and antioxidant property. In the in vivo study, C57BL/6 J mice were orally administered 100 mg/kg carvacrol for 4 weeks and confirmed a decreased size of endometriosis lesions in the carvacrol-treated group, increased number of T cells in the spleen, and increased expression of cytokine-related genes in both tissues. Immortalized human ovarian endometriotic stromal cells (ihOESCs), derived from endometriotic lesions in patients, were used as an in vitro model for studying endometriosis pathophysiology. The findings of the in vitro study confirmed that carvacrol regulates calcium homeostasis, induces antioxidant effects, increases inflammatory response, deactivates the phosphatidylinositol 3-kinase (PI3K) signaling pathway, and ultimately induces autophagy. Therefore, we determined that carvacrol is suitable as an anti-inflammatory and anti-oxidant treatment strategy for endometriosis. Graphical Abstract Similar content being viewed by others Data Availability Data available on request from the authors. Code Availability Not applicable.

References

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Acknowledgements

This research was supported by a grant of 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: HI22 C1424). And this research was supported by 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 Hyewon Jang: Investigation, Methodology, Software, Writing-Original draft preparation; Wonhyoung Park: Investigation, Methodology, Software, Writing-Original draft preparation; Hee Seung Kim: Methodology, Validation; Gwonhwa Song: Conceptualization, Validation, Supervision; Whasun Lim: Validation, Supervision, Writing- Review & Editing; Sunwoo Park: Conceptualization, Writing- Review & Editing, Funding Acquisition. Corresponding authors Ethics declarations Ethics Approval The animal experiments were conducted according to the approval of the IACUC at Gyeongsang National University (GNU- 220314-M0027). Consent to Participate Not applicable. Consent for Publication Not applicable. Conflict of Interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. 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 Jang, H., Park, W., Kim, H.S. et al. Carvacrol Shows Potential as a Treatment for Endometriosis with Inflammatory Reaction and Antioxidant Properties, Demonstrated in both In Vivo and In Vitro Studies. Reprod. Sci. 32, 1825–1839 (2025). https://doi.org/10.1007/s43032-025-01866-y Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-025-01866-y

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endometriosis

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Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents Anti-Inflammatory Agents

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