Honokiol inhibits cell migration and invasion by blocking EMT via Snail/Slug axis in endometriosis

Endometriosis, a common gynecological disease, leads to dysmenorrhea and infertility. EMT process was closely related to the pathology of endometriosis. More therapies were required to be explored for endometriosis management. The current study was intended to explore the effect of honokiol in endometriosis. Endometriosis endometrial stromal cells (EESCs) were isolated from endometriosis patients for in vitro analysis. Rats were autotransplanted with endometrial tissues for in vivo study. A range of experiments including MTT, wound healing, Transwell, western blot, hematoxylin and eosin staining, immunohistochemical staining, and RIA analysis were carried out to determine the function and mechanism of honokiol in vitro and in vivo. For in vitro analysis, low dose of honokiol treatment induced no cytotoxicity to EESCs. Honokiol treatment suppressed cell migration and invasion of EESCs. Additionally, honokiol inhibited EMT process of EESCs. For in vivo analysis, honokiol treatment significantly improved pathological morphology in endometriosis model rats. Besides, honokiol treatment decreased Ki67 but increased cleaved caspase-3 protein in ectopic endometrium tissues. Moreover, honokiol administration decreased wet weight of ectopic endometrium tissues, E2 and PGE2 levels. Similarly, honokiol also attenuated EMT process in ectopic endometrium tissues. In summary, honokiol inhibits cell migration and invasion by blocking EMT via Snail/Slug axis in endometriosis, which may provide another choice for endometriosis treatment. Similar content being viewed by others Data availability All data generated or analyzed during the current study are available from the corresponding author on reasonable request.

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We appreciate the support of the First Hospital of Hunan University of Chinese Medicine. Funding Hunan Natural Science Foundation Project (No. 2025JJ80931). Joint Fund of Hunan University of Traditional Chinese Medicine (No. 2024XYLH350). Scientific Research Fund of the Health Commission of Hunan Province (No. 20254619). Author information Authors and Affiliations Contributions Xiaojuan Kong conceived and designed the experiments. Xiaojuan Kong and Lei Lei carried out the experiments.Xiaojuan Kong and Lei Lei analyzed the data. Xiaojuan Kong and Lei Lei drafted the manuscript. All authors agreed to be accountable for all aspects of the work. All authors have read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used. Corresponding author Ethics declarations Ethics approval and consent to participate All participants provided informed consent. The study complied with the Declaration of Helsinki and was approved by the Ethics Committee of the First Hospital of Hunan University of Chinese Medicine. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Clinical trial number Not applicable. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. ESM 1 (download PPTX ) (PPTX 2.14 MB) 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 Kong, X., Lei, L. Honokiol inhibits cell migration and invasion by blocking EMT via Snail/Slug axis in endometriosis. Naunyn-Schmiedeberg's Arch Pharmacol 399, 4507–4517 (2026). https://doi.org/10.1007/s00210-025-04702-x Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00210-025-04702-x