Scutellarin Suppresses Platelet Aggregation and Stalls Lesional Progression in Mouse With Induced Endometriosis

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Scutellarin treatment reduced endometriosis lesion weight and pain in mice by suppressing platelet aggregation, proliferation, angiogenesis, and fibrogenesis.

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This study evaluated scutellarin, a flavonoid with antiplatelet activity, in a mouse model of induced endometriosis created by intraperitoneal injection of uterine fragments into 27 female Balb/c mice. After induction, mice received either vehicle or low- or high-dose scutellarin, and investigators assessed peripheral platelet activation/aggregation plus lesion outcomes including total lesion weight, hyperalgesia, and lesion histology markers of proliferation, angiogenesis, fibroblast-to-myofibroblast transdifferentiation, and fibrosis. Compared with untreated controls, scutellarin lowered activated platelet rates and reduced platelet aggregation, alongside reduced lesion size and improved pain behavior, with decreased proliferation, angiogenesis, FMT, and fibrosis in lesions. This paper is centrally about endometriosis — it tests scutellarin’s antiplatelet effects on lesion progression and associated pain in an experimentally induced endometriosis model.

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Abstract

Platelets play an important role in the development of endometriosis. Scutellarin is a flavonoid isolated from a medicinal herb traditionally used as a potent antiplatelet agent. In this study, we sought to evaluate its potential therapeutic effect, if any, in mice with induced endometriosis. Endometriosis was induced in 27 female Balb/c mice by intraperitoneal injection of uterine fragments. Two weeks after the induction, the 27 mice were randomly divided in equal sizes into 3 groups: untreated, which received only vehicle, and low-dose and high-dose groups, which received low- and high dose of scutellarin treatment. Hotplate test was administrated to all mice before endometriosis induction, and before and after the scutellarin treatment. Two weeks after the treatment, a blood sample was drawn before sacrifice and all lesions were harvested. The peripheral platelet activation rate and total lesion weight were assessed, and immunohistochemistry and histochemistry analyses were performed to evaluate the extent of proliferation, angiogenesis, fibroblast-to-myofibroblast transdifferentiation (FMT), and fibrosis in lesions. Compared with untreated mice, mice in both low-dose and high-dose groups had significantly reduced lesion weight and improved hyperalgesia. Scutellarin also reduced the peripheral-activated platelets rate and resulted in significantly reduced platelet aggregation, cellular proliferation, angiogenesis, the extent of FMT, and the extent of fibrosis in lesions. Thus, we conclude that scutellarin is efficacious in treating endometriosis in vivo by suppressing platelet aggregation, inhibiting proliferation, angiogenesis, and fibrogenesis, resulting in reduced lesion size and improved pain behavior. As such, scutellarin may be a potentially promising therapeutics for the treatment of endometriosis. Similar content being viewed by others

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Author information Authors and Affiliations Corresponding authors Supplemental Material Supplemental Material Supplemental material for this article is available online. Rights and permissions About this article Cite this article Ding, D., Cai, X., Zheng, H. et al. Scutellarin Suppresses Platelet Aggregation and Stalls Lesional Progression in Mouse With Induced Endometriosis. Reprod. Sci. 26, 1417–1428 (2019). https://doi.org/10.1177/1933719118817661 Published: Version of record: Issue date: DOI: https://doi.org/10.1177/1933719118817661

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mesh:D004715endometriosis

MeSH descriptors

Apigenin Endometriosis Glucuronates Pain Measurement Pain Measurement Platelet Aggregation Animals Apigenin Apigenin Endometriosis Endometriosis Endometriosis Female Glucuronates Glucuronates Mice Mice, Inbred BALB C Pain Measurement Platelet Aggregation Platelet Aggregation

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