Quercetin and Ferulic Acid Elicit Estrogenic Activities In Vivo and In Silico

Abstract

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.

Unlocking the Potential: Quercetin and Its Natural Derivatives as Promising Therapeutics for Sepsis

“…Athletes using this quercetin supplement had better improvement in symptoms, such as muscle or local pain, spasms, and reduced levels of oxidative stress compared to controls [99]. No side effects were reported [98,99], and no hepatic or renal toxicity was observed [100]. It has been claimed that the use of the supplement may be effective in reducing some of the symptoms of pollen-induced allergies [101].…”

Sex Related Differences in the Complex Relationship between Coffee, Caffeine and Atrial Fibrillation

“…Ferulic acid is another polyphenol present in coffee with antioxidant and anti-inflammatory properties [65]. Ferulic acid can be found in cereals, fruits and vegetables [66].…”

Effect of quercetin on doxorubicin cytotoxicity in sensitive and resistant human MCF7 breast cancer cell lines

“…Quercetin is a polyphenolic compound that is found in abundance in a number of fruits, vegetables and plants and exerts various biological effects, such as antioxidant, antiviral, anticancer, cell cycle modulatory and anti-angiogenesis effects ( 19 ). It has been reported that quercetin is effective in inhibiting cancer cell growth via the induction of apoptosis ( 20 , 21 ). In addition, quercetin has been reported to upregulate the expression of estrogen receptors α and β.…”