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槲皮素在来曲唑诱导的多囊卵巢综合征大鼠模型中的治疗潜力:组织学和生化研究。

Therapeutic potentials of Quercetin in management of polycystic ovarian syndrome using Letrozole induced rat model: a histological and a biochemical study.

机构信息

Department of Animal Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan.

出版信息

J Ovarian Res. 2018 Apr 3;11(1):26. doi: 10.1186/s13048-018-0400-5.

Abstract

BACKGROUND

PCOS is a leading endocrinopathy of young women instigating androgens elevation, insulin resistance, obesity, cardiometabolic and menstrual complications. The study investigated the effects of quercetin in a letrozole induced rat model of polycystic ovarian syndrome, which displayed both clinical and metabolic features as in PCOS women.

METHODS

Female Sprague Dawley (SD) rats were divided into four groups; control group received aqueous solution of carboxymethyl (CMC 0.5%); PCOS group administered with letrozole (1 mg/kg) dissolved in solution (CMC 0.5%); Metformin group given with metformin (20 mg/kg) + letrozole (1 mg/kg); and Quercetin group provided with quercetin (30 mg/kg) + letrozole (1 mg/kg). All doses were given orally via gavage, for 21 consecutive days and colpocytological analysis was carried till end. After 21rst day, blood was taken out, centrifuged and plasma was kept for biochemical analysis (ELISA, anti-oxidant enzymes, lipid profile) and the reproductive organs were dissected out for histopathological evaluation.

RESULTS

Quercetin as a chief member of flavonoid, showed beneficial effects by decreasing body weight, ovarian diameter, cysts and restoring healthy follicles, follicle's extra-glandular layers, and corpora lutea in contrast to the positive control. Additionally, lipid profile and anti-oxidant status were also maintained to baseline which was very high in diseased rats (p < 0.001).Quercetin depicted a mark regulation in steroidogenesis by decreasing the levels of testosterone (0.78 ng/ml ± 0.14 in quercetin vs. PCOS positive control 1.69 ng/ml ± 0.17, p < 0.001) and estradiol (8.85 pg/ml ± 0.19 in quercetin vs. PCOS positive 1.61 pg/ml ± 0.29) and increasing progesterone levels (34.47 ng/ml ± 1.65 in quercetin vs. 11.08 ng/ml ± 1.17 in PCOS positive). The effects of quercetin were moderately parallel to the standard drug available in market i.e. metformin.

CONCLUSION

The present study has confirmed that quercetin has the potentials to alleviate the hormonal and metabolic disturbances occurring in PCOS.

摘要

背景

多囊卵巢综合征(PCOS)是一种常见的年轻女性内分泌疾病,会导致雄激素升高、胰岛素抵抗、肥胖、心脏代谢和月经紊乱等问题。本研究旨在探讨槲皮素在来曲唑诱导的多囊卵巢综合征大鼠模型中的作用,该模型具有 PCOS 女性的临床和代谢特征。

方法

将雌性 Sprague Dawley(SD)大鼠分为四组:对照组给予羧甲基纤维素(CMC 0.5%)水溶液;PCOS 组给予来曲唑(1mg/kg)溶于 CMC 0.5%溶液;二甲双胍组给予二甲双胍(20mg/kg)+来曲唑(1mg/kg);槲皮素组给予槲皮素(30mg/kg)+来曲唑(1mg/kg)。所有剂量均通过灌胃给药,连续 21 天,同时进行阴道细胞学分析。第 21 天取血,离心后取血浆进行生化分析(ELISA、抗氧化酶、血脂谱),并取出生殖器官进行组织病理学评估。

结果

槲皮素作为黄酮类化合物的主要成分,通过降低体重、卵巢直径、囊肿数量以及恢复健康的卵泡、卵泡外腺层和黄体,显示出有益的效果,与阳性对照组相比。此外,还维持了血脂谱和抗氧化状态,这在患病大鼠中非常高(p<0.001)。槲皮素通过降低睾酮水平(槲皮素组 0.78ng/ml±0.14,PCOS 阳性对照组 1.69ng/ml±0.17,p<0.001)和雌二醇水平(槲皮素组 8.85pg/ml±0.19,PCOS 阳性对照组 1.61pg/ml±0.29),同时增加孕酮水平(槲皮素组 34.47ng/ml±1.65,PCOS 阳性对照组 11.08ng/ml±1.17),对甾体激素生成具有显著的调节作用。槲皮素的作用与市场上现有的标准药物二甲双胍相当。

结论

本研究证实槲皮素有缓解 PCOS 患者发生的激素和代谢紊乱的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a0e/5883607/7fa87ee5e9ad/13048_2018_400_Fig1_HTML.jpg

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