Laboratory of Biotechnology, Environment, Agro-Food, and Health (LBEAS), Faculty of Sciences, University 7 Sidi-Mohamed-Ben-Abdellah (USMBA), Fez 30050, Morocco.
Biomedical and Translational Research Laboratory, Faculty of Medicine and Pharmacy of Fez, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco.
Molecules. 2023 Jun 29;28(13):5112. doi: 10.3390/molecules28135112.
In this study, we examined the sub-acute toxicity of quercetin and ferulic acid and evaluated their effects on protein, cholesterol, and estrogen levels in vivo. Six groups of female Wistar rats were fed by gavage. The first and second groups represent the positive (Clomiphene citrate 10 mg/kg) and negative (NaCl 0.9%) control groups, while the other groups received quercetin and ferulic acid at doses of 5 and 10 mg/kg/day for 28 days. The sub-acute toxicity was monitored by examining the weights, biochemical parameters (AST, ALT, ALP, urea, and CREA), and histological changes in the kidneys and liver of the treated animals. Furthermore, the in vivo estrogenic effects were studied in terms of the serum and ovarian cholesterol levels, serum estradiol, and uterine proteins. Finally, Docking studies were conducted to evaluate the binding affinity of quercetin and ferulic acid for alpha and beta estrogen receptors. Results showed that both compounds were devoid of any signs of nephrotoxicity or hepatotoxicity. Additionally, quercetin and ferulic acid caused significant estrogenic effects evidenced by an increase of 8.7 to 22.48% in serum estradiol, though to a lesser amount than in the reference drug-treated group (64.21%). Moreover, the two compounds decreased the serum cholesterol levels (12.26-32.75%) as well as the ovarian cholesterol level (11.9% to 41.50%) compared to the negative control. The molecular docking in estrogen alpha and estrogen beta active sites showed high affinity of quercetin (-10.444 kcal/mol for estrogen alpha and -10.662 kcal/mol for estrogen beta) and ferulic acid (-6.377 kcal/mol for estrogen alpha and -6.3 kcal/mol for estrogen beta) to these receptors. This study provides promising insights into the potential use of quercetin as a therapeutic agent for the management of female fertility issues.
在这项研究中，我们研究了槲皮素和阿魏酸的亚急性毒性，并评估了它们对体内蛋白质、胆固醇和雌激素水平的影响。我们给六组雌性 Wistar 大鼠进行灌胃。第一组和第二组分别为阳性（枸橼酸氯米酚 10mg/kg）和阴性（0.9%氯化钠）对照组，而其他组则分别给予 5 和 10mg/kg/天的槲皮素和阿魏酸，连续 28 天。通过检查处理动物的体重、生化参数（AST、ALT、ALP、尿素和 CREA）以及肾脏和肝脏的组织学变化，监测亚急性毒性。此外，还研究了体内雌激素作用，包括血清和卵巢胆固醇水平、血清雌二醇和子宫蛋白。最后，进行了对接研究，以评估槲皮素和阿魏酸与 alpha 和 beta 雌激素受体的结合亲和力。结果表明，这两种化合物都没有任何肾毒性或肝毒性的迹象。此外，槲皮素和阿魏酸引起了明显的雌激素作用，血清雌二醇增加了 8.7%至 22.48%，尽管比参考药物处理组（64.21%）要少。此外，这两种化合物降低了血清胆固醇水平（12.26%-32.75%）和卵巢胆固醇水平（11.9%-41.50%），与阴性对照组相比。在雌激素 alpha 和雌激素 beta 的活性部位进行分子对接表明，槲皮素（雌激素 alpha 为-10.444kcal/mol，雌激素 beta 为-10.662kcal/mol）和阿魏酸（雌激素 alpha 为-6.377kcal/mol，雌激素 beta 为-6.3kcal/mol）与这些受体具有很高的亲和力。这项研究为槲皮素作为治疗女性生育问题的治疗剂的潜在用途提供了有希望的见解。
