Resveratrol-βcd inhibited premature ovarian insufficiency progression by regulating granulosa cell autophagy
Abstract Background The ovarian environment of premature ovarian insufficiency (POI) patients exhibits immune dysregulation, which leads to excessive secretion of numerous proinflammatory cytokines that affect ovarian function. An abnormal level of macrophage polarization directly or indirectly inhi...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Journal of Ovarian Research |
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| Online Access: | https://doi.org/10.1186/s13048-024-01344-0 |
| _version_ | 1827377217910341632 |
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| author | Bingbing Hu Xiushuang Zheng Wei Zhang |
| author_facet | Bingbing Hu Xiushuang Zheng Wei Zhang |
| author_sort | Bingbing Hu |
| collection | DOAJ |
| description | Abstract Background The ovarian environment of premature ovarian insufficiency (POI) patients exhibits immune dysregulation, which leads to excessive secretion of numerous proinflammatory cytokines that affect ovarian function. An abnormal level of macrophage polarization directly or indirectly inhibits the differentiation of ovarian granulosa cells and steroid hormone production, ultimately leading to POI. Resveratrol, as a health supplement, has been widely recognized for its safety. There is a substantial amount of evidence indicating that resveratrol and its analogs possess significant immune-regulatory functions. It has also been reported that resveratrol can effectively inhibit the progression of POI. However, the underlying immunological and molecular mechanisms through which resveratrol inhibits the progression of POI are still unclear. Results Our preliminary reports have shown that resveratrol-βcd, the beta-cyclodextrin complex of resveratrol, significantly enhances the stability of resveratrol. Resveratrol-βcd could regulate the dysfunctional immune status of macrophages and T cells in the tumor microenvironment. In this study, we treated busulfan and cyclophosphamide (B/C)-treated mice, which were used as a POI model, with resveratrol-βcd. After resveratrol-βcd treatment, the levels of IL-6 in the ovaries were significantly increased, and the progression of POI was suppressed. IL-6 activated granulosa cells (GCs) through soluble IL-6R (sIL-6R), promoting autophagy in GCs. Resveratrol-βcd and IL-6 had a synergistic effect on enhancing autophagy in GCs and promoting E2 secretion. Conclusions We partially elucidated the immune mechanism by which resveratrol inhibits the progression of POI and the autophagy-regulating function of GCs. This provides a theoretical basis for using resveratrol to prevent POI in future studies and clinical guidance. |
| first_indexed | 2024-03-08T12:35:51Z |
| format | Article |
| id | doaj.art-d1735befa63f4cd4bd3466346737273a |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-03-08T12:35:51Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-d1735befa63f4cd4bd3466346737273a2024-01-21T12:30:37ZengBMCJournal of Ovarian Research1757-22152024-01-0117111410.1186/s13048-024-01344-0Resveratrol-βcd inhibited premature ovarian insufficiency progression by regulating granulosa cell autophagyBingbing Hu0Xiushuang Zheng1Wei Zhang2The Reproductive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Reproductive Medicine, The First Affiliated Hospital of Harbin Medical UniversityEmergency and Disaster Medical Center, The Seventh Affiliated Hospital, Sun Yat-Sen UniversityAbstract Background The ovarian environment of premature ovarian insufficiency (POI) patients exhibits immune dysregulation, which leads to excessive secretion of numerous proinflammatory cytokines that affect ovarian function. An abnormal level of macrophage polarization directly or indirectly inhibits the differentiation of ovarian granulosa cells and steroid hormone production, ultimately leading to POI. Resveratrol, as a health supplement, has been widely recognized for its safety. There is a substantial amount of evidence indicating that resveratrol and its analogs possess significant immune-regulatory functions. It has also been reported that resveratrol can effectively inhibit the progression of POI. However, the underlying immunological and molecular mechanisms through which resveratrol inhibits the progression of POI are still unclear. Results Our preliminary reports have shown that resveratrol-βcd, the beta-cyclodextrin complex of resveratrol, significantly enhances the stability of resveratrol. Resveratrol-βcd could regulate the dysfunctional immune status of macrophages and T cells in the tumor microenvironment. In this study, we treated busulfan and cyclophosphamide (B/C)-treated mice, which were used as a POI model, with resveratrol-βcd. After resveratrol-βcd treatment, the levels of IL-6 in the ovaries were significantly increased, and the progression of POI was suppressed. IL-6 activated granulosa cells (GCs) through soluble IL-6R (sIL-6R), promoting autophagy in GCs. Resveratrol-βcd and IL-6 had a synergistic effect on enhancing autophagy in GCs and promoting E2 secretion. Conclusions We partially elucidated the immune mechanism by which resveratrol inhibits the progression of POI and the autophagy-regulating function of GCs. This provides a theoretical basis for using resveratrol to prevent POI in future studies and clinical guidance.https://doi.org/10.1186/s13048-024-01344-0ResveratrolPremature ovarian insufficiency (POI)Granulosa cells (GCs)MacrophageIL-6 |
| spellingShingle | Bingbing Hu Xiushuang Zheng Wei Zhang Resveratrol-βcd inhibited premature ovarian insufficiency progression by regulating granulosa cell autophagy Journal of Ovarian Research Resveratrol Premature ovarian insufficiency (POI) Granulosa cells (GCs) Macrophage IL-6 |
| title | Resveratrol-βcd inhibited premature ovarian insufficiency progression by regulating granulosa cell autophagy |
| title_full | Resveratrol-βcd inhibited premature ovarian insufficiency progression by regulating granulosa cell autophagy |
| title_fullStr | Resveratrol-βcd inhibited premature ovarian insufficiency progression by regulating granulosa cell autophagy |
| title_full_unstemmed | Resveratrol-βcd inhibited premature ovarian insufficiency progression by regulating granulosa cell autophagy |
| title_short | Resveratrol-βcd inhibited premature ovarian insufficiency progression by regulating granulosa cell autophagy |
| title_sort | resveratrol βcd inhibited premature ovarian insufficiency progression by regulating granulosa cell autophagy |
| topic | Resveratrol Premature ovarian insufficiency (POI) Granulosa cells (GCs) Macrophage IL-6 |
| url | https://doi.org/10.1186/s13048-024-01344-0 |
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