Pharmacology Department, Bogomolets National Medical University, 01601 Kyiv, Ukraine.
Department of Clinical Pharmacology, Institute of Improvement Qualification of Pharmacy Specialists, National University of Pharmacy, 61002 Kharkiv, Ukraine.
Molecules. 2022 Aug 2;27(15):4916. doi: 10.3390/molecules27154916.
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% (p < 0.001), less pronounced symptom of fever at the root of the tail by 9% (p < 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 (p < 0.001) and elevated Bcl-2 score in endometrial glands (p = 0.01). Together with enhanced VEGF expression in endometrial glands (p < 0.001) and stromal cells (p = 0.007), these changes prevented endometrial atrophy (p < 0.001) after ovariectomy. Thus, this study substantiates the feasibility of developing an innovative topical drug with R and HA for treating hypoestrogenic disorders.
植物雌激素白藜芦醇（R）已被证明有益于人类生殖健康。然而，口服补充 R 时，其生物利用度和药代动力学仍然存在问题。我们使用含有 R 和透明质酸（HA）的实验性阴道凝胶来提高生物利用度和药代动力学特性。本研究旨在评估阴道 R-HA 凝胶对去卵巢大鼠生殖系统的影响。
本研究在 Wistar 雌性大鼠上进行。研究了体重、尾巴温度、阴道 pH 值、雌激素和孕激素的血液水平以及免疫组织化学生物标志物（COX2、Casp-3、Bcl-2 和 VEGF）。动物分为对照组；去卵巢大鼠（OVX）；以及 OVX 组用阴道 0.5%R-HA 凝胶（0.5%，0.1 mL，每日 28 天）治疗。
R-HA 凝胶的治疗效果表现为体重增加减缓 17%（p<0.001），尾巴根部发热症状不明显减少 9%（p<0.001），阴道 pH 值降低至 4.4-4.5，与 OVX 大鼠相比。RA-H 在阴道中的抗炎作用和 COX-2 表达减少伴随着子宫内膜的抗凋亡作用，这与 Casp-3 表达降低（p<0.001）和子宫内膜腺中 Bcl-2 评分升高（p=0.01）有关。与子宫内膜腺和基质细胞中 VEGF 表达增强（p<0.001）一起，这些变化防止了去卵巢后的子宫内膜萎缩（p<0.001）。因此，本研究证实了开发含有 R 和 HA 的创新局部药物治疗低雌激素疾病的可行性。
