Resveratrol Effects on the Reproductive System in Ovariectomized Rats: Deciphering Possible Mechanisms
Phytoestrogen resveratrol (R) has been demonstrated to benefit human reproductive health. However, R bioavailability and pharmacokinetics are still problematic under oral supplementation. We used an experimental vaginal gel with R and hyaluronic acid (HA) to improve bioavailability and pharmacokinet...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/15/4916 |
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| author | Ganna Zaychenko Olena Stryga Oksana Sinitsyna Anna Doroshenko Oksana Sulaieva Tetyana Falalyeyeva Nazarii Kobyliak |
| author_facet | Ganna Zaychenko Olena Stryga Oksana Sinitsyna Anna Doroshenko Oksana Sulaieva Tetyana Falalyeyeva Nazarii Kobyliak |
| author_sort | Ganna Zaychenko |
| collection | DOAJ |
| description | Phytoestrogen resveratrol (R) has been demonstrated to benefit human reproductive health. However, R bioavailability and pharmacokinetics are still problematic under oral supplementation. We used an experimental vaginal gel with R and hyaluronic acid (HA) to improve bioavailability and pharmacokinetic properties. The study aimed to assess the impact of vaginal R-HA gel on the reproductive system in ovariectomized rats. Methods: The study was carried out on Wistar female rats. It investigated the body weight, tail temperature, vaginal pH, estrogen and progesterone blood levels, and immunohistochemical biomarkers (COX2, Casp-3, Bcl-2, and VEGF). Animals were divided into control animals; ovariectomized rats (OVX); and OVX group treated with vaginal 0.5% R-HA gel (0.5%, 0.1 mL, daily 28 days). Results: The R-HA gel’s therapeutic effect was manifested by slowing weight gain by 17% (<i>p</i> < 0.001), less pronounced symptom of fever at the root of the tail by 9% (<i>p</i> < 0.001) and lowering the vaginal pH to 4.4–4.5 compared with OVX rats. The anti-inflammatory effect and the reduction of COX-2 expression in vagina were accompanied by antiapoptotic impact of RA-H on endometrium, associated with the decreased Casp-3 expression (<i>p</i> < 0.001) and elevated Bcl-2 score in endometrial glands (<i>p</i> = 0.01). Together with enhanced VEGF expression in endometrial glands (<i>p</i> < 0.001) and stromal cells (<i>p</i> = 0.007), these changes prevented endometrial atrophy (<i>p</i> < 0.001) after ovariectomy. Thus, this study substantiates the feasibility of developing an innovative topical drug with R and HA for treating hypoestrogenic disorders. |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T10:06:30Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-5c583365bd45425f87fe568c1f0d30002023-12-01T23:03:29ZengMDPI AGMolecules1420-30492022-08-012715491610.3390/molecules27154916Resveratrol Effects on the Reproductive System in Ovariectomized Rats: Deciphering Possible MechanismsGanna Zaychenko0Olena Stryga1Oksana Sinitsyna2Anna Doroshenko3Oksana Sulaieva4Tetyana Falalyeyeva5Nazarii Kobyliak6Pharmacology Department, Bogomolets National Medical University, 01601 Kyiv, UkrainePharmacology Department, Bogomolets National Medical University, 01601 Kyiv, UkraineDepartment of Clinical Pharmacology, Institute of Improvement Qualification of Pharmacy Specialists, National University of Pharmacy, 61002 Kharkiv, UkrainePharmacology Department, Bogomolets National Medical University, 01601 Kyiv, UkraineMedical Laboratory CSD, 03122 Kyiv, UkraineMedical Laboratory CSD, 03122 Kyiv, UkraineMedical Laboratory CSD, 03122 Kyiv, UkrainePhytoestrogen resveratrol (R) has been demonstrated to benefit human reproductive health. However, R bioavailability and pharmacokinetics are still problematic under oral supplementation. We used an experimental vaginal gel with R and hyaluronic acid (HA) to improve bioavailability and pharmacokinetic properties. The study aimed to assess the impact of vaginal R-HA gel on the reproductive system in ovariectomized rats. Methods: The study was carried out on Wistar female rats. It investigated the body weight, tail temperature, vaginal pH, estrogen and progesterone blood levels, and immunohistochemical biomarkers (COX2, Casp-3, Bcl-2, and VEGF). Animals were divided into control animals; ovariectomized rats (OVX); and OVX group treated with vaginal 0.5% R-HA gel (0.5%, 0.1 mL, daily 28 days). Results: The R-HA gel’s therapeutic effect was manifested by slowing weight gain by 17% (<i>p</i> < 0.001), less pronounced symptom of fever at the root of the tail by 9% (<i>p</i> < 0.001) and lowering the vaginal pH to 4.4–4.5 compared with OVX rats. The anti-inflammatory effect and the reduction of COX-2 expression in vagina were accompanied by antiapoptotic impact of RA-H on endometrium, associated with the decreased Casp-3 expression (<i>p</i> < 0.001) and elevated Bcl-2 score in endometrial glands (<i>p</i> = 0.01). Together with enhanced VEGF expression in endometrial glands (<i>p</i> < 0.001) and stromal cells (<i>p</i> = 0.007), these changes prevented endometrial atrophy (<i>p</i> < 0.001) after ovariectomy. Thus, this study substantiates the feasibility of developing an innovative topical drug with R and HA for treating hypoestrogenic disorders.https://www.mdpi.com/1420-3049/27/15/4916resveratrolpolyphenolshyaluronic acidmenopausehypoestrogenic disordersvaginal gel |
| spellingShingle | Ganna Zaychenko Olena Stryga Oksana Sinitsyna Anna Doroshenko Oksana Sulaieva Tetyana Falalyeyeva Nazarii Kobyliak Resveratrol Effects on the Reproductive System in Ovariectomized Rats: Deciphering Possible Mechanisms Molecules resveratrol polyphenols hyaluronic acid menopause hypoestrogenic disorders vaginal gel |
| title | Resveratrol Effects on the Reproductive System in Ovariectomized Rats: Deciphering Possible Mechanisms |
| title_full | Resveratrol Effects on the Reproductive System in Ovariectomized Rats: Deciphering Possible Mechanisms |
| title_fullStr | Resveratrol Effects on the Reproductive System in Ovariectomized Rats: Deciphering Possible Mechanisms |
| title_full_unstemmed | Resveratrol Effects on the Reproductive System in Ovariectomized Rats: Deciphering Possible Mechanisms |
| title_short | Resveratrol Effects on the Reproductive System in Ovariectomized Rats: Deciphering Possible Mechanisms |
| title_sort | resveratrol effects on the reproductive system in ovariectomized rats deciphering possible mechanisms |
| topic | resveratrol polyphenols hyaluronic acid menopause hypoestrogenic disorders vaginal gel |
| url | https://www.mdpi.com/1420-3049/27/15/4916 |
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