Natural bioactive compounds and herbal medicines targeting common signaling pathways in endometriosis: mechanisms and therapeutic implications

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This review examines natural compounds and herbal medicines for endometriosis, highlighting their multi-target therapeutic potential and mechanisms of action against the condition.

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This paper is a review discussing how natural bioactive compounds and herbal medicines may target signaling pathways relevant to endometriosis, focusing on evidence for crude and refined plant extracts and their multi-target mechanisms. It summarizes that endometriosis involves ectopic endometrioid tissue growth driven by persistent inflammation and estrogen dependence, while current treatments rely mainly on NSAIDs and hormonal therapies (with potential adverse effects) or surgery (with recurrence rates reported as 21.5% after 2 years and up to 50% within 5 years). The key finding is that plant-derived agents can act on multiple targets/pathways implicated in endometriosis, but the authors explicitly emphasize the need for further pre-clinical and clinical studies to establish effective, safer natural treatment strategies. This paper is centrally about endometriosis — it reviews herbal medicines and bioactive compounds targeting signaling pathways in endometriosis.

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Abstract

For a very long time, herbal treatments have served as remedies for various humans and animals. Natural compounds typically have multiple pharmacological actions because they interact with various biological targets. This characteristic could be exploited to effectively treat disorders with complex physiopathological causes, such as endometriosis. Endometriosis is the proliferation, infiltration, and recurrent bleeding of endometrioid tissue, including stroma and glands, outside the uterine cavity, forming nodules or masses. It affects women of reproductive age and is characterized by persistent inflammation and estrogen dependence, significantly impacting patients' quality of life. Although the precise pathogenic mechanisms remain unclear, current treatments mainly include medication and surgery. Pharmacotherapy typically relies on nonsteroidal anti-inflammatory drugs and hormonal agents, which may cause adverse effects such as gastrointestinal disturbances, hepatic and renal dysfunction, and thrombosis when used as a long-term treatment. Surgical removal of lesions is possible but often followed by recurrence rates of 21.5% after 2 years and up to 50% within 5 years. Therefore, alternative or complementary therapeutic approaches are urgently needed. This review summarizes current evidence on bioactive plant extracts, both crude and refined, and their mechanisms of action against endometriosis, highlighting their multi-target therapeutic potential and underscoring the need for further pre-clinical and clinical studies to develop effective, safer natural treatment strategies.
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Abstract

For a very long time, herbal treatments have served as remedies for various humans and animals. Natural compounds typically have multiple pharmacological actions because they interact with various biological targets. This characteristic could be exploited to effectively treat disorders with complex physiopathological causes, such as endometriosis. Endometriosis is the proliferation, infiltration, and recurrent bleeding of endometrioid tissue, including stroma and glands, outside the uterine cavity, forming nodules or masses. It affects women of reproductive age and is characterized by persistent inflammation and estrogen dependence, significantly impacting patients’ quality of life. Although the precise pathogenic mechanisms remain unclear, current treatments mainly include medication and surgery. Pharmacotherapy typically relies on nonsteroidal anti-inflammatory drugs and hormonal agents, which may cause adverse effects such as gastrointestinal disturbances, hepatic and renal dysfunction, and thrombosis when used as a long-term treatment. Surgical removal of lesions is possible but often followed by recurrence rates of 21.5% after 2 years and up to 50% within 5 years. Therefore, alternative or complementary therapeutic approaches are urgently needed. This review summarizes current evidence on bioactive plant extracts, both crude and refined, and their mechanisms of action against endometriosis, highlighting their multi-target therapeutic potential and underscoring the need for further pre-clinical and clinical studies to develop effective, safer natural treatment strategies. Similar content being viewed by others Data availability All source data for this work (or generated in this study) are available upon reasonable request.

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Author information Authors and Affiliations Contributions All authors have contributed equally to this work. The authors confirm that no paper mill and artificial intelligence was used. Corresponding author Ethics declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Animal ethics declaration Not applicable. Competing interests The authors declare no competing interests. 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 Elbanna, A.H., El-Dessouki, A.M., Mageed, S.S.A. et al. Natural bioactive compounds and herbal medicines targeting common signaling pathways in endometriosis: mechanisms and therapeutic implications. Naunyn-Schmiedeberg's Arch Pharmacol 399, 6249–6288 (2026). https://doi.org/10.1007/s00210-025-04797-2 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00210-025-04797-2

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