Differential effects of genistein and 8-prenylgenistein on reproductive tissues in immature female mice

Abstract

Context: We identified an active prenylated derivative of genistein, 8-prenylgenistein (8PG) from Erythrina variegata L. (Leguminosae) and found that 8PG increased osteoprotective effects of genistein in oestrogen-deficient mice. Objective: This study investigated and compared the oestrogenic effects of genistein and 8PG on uterus and vagina of immature mice. Materials and methods: Immature female CD-1 mice were orally treated with vehicle (Control, n = 10) or genistein (75 mg/kg, n = 10) or 8PG with low (8PG-L, 75 mg/kg, n = 10) and high dose (8PG-H, 150 mg/kg, n = 10) for 7 consecutive days by intragastric gavage. The uterus and vagina were harvested for histological and molecular measurements. Results: Treatment with genistein and 8PG-H significantly increased uterus index (1.98 ± 0.21 & 1.49 ± 0.16 mg/g) and vagina index (3.83 ± 0.11 & 3.13 ± 0.25 mg/g) as compared to untreated control (uterus, 1.12 ± 0.13 mg/g; vagina, 2.32 ± 0.18 mg/g). Accordingly, both genistein and 8PG-H made vaginal cells keratinized and induced uterine and vaginal hypertrophy associated with the endometrial proliferation. 8PG-L did not affect oestrus cycle and histology of uterus and vagina. Treatment of immature mice with genistein or 8PG-H upregulated protein expression of oestrogen receptor-α (ER-α) and proliferating cell nuclear antigen (PCNA), but 8PG-L did not alter ER-α and PCNA expression in uterus and vagina. Conclusion: This study indicated that 8-prenylgenistein exerted oestrogenic effects in immature female mice. The efficacy and safety of 8-prenylgenistein when applied in improving oestrogen deficiency-induced syndrome requires further elucidation.

Pharmacology activity, toxicity, and clinical trials of Erythrina genus plants (Fabaceae): an evidence-based review

“…Erythrina plants have also been explored for other activities, e.g., estrogenic activity by increasing uterus and vaginal index and keratinizing vaginal cells, inducing uterine and vaginal hypertrophy associated with endometrial proliferation (Li et al, 2019), antiviral against respiratory syncytial virus (RSV) and herpes simplex virus (HSV-2) (Mollel et al, 2022), strong antifungal activities against Candida albicans and C. glabrata strains and clinical isolates (Harley et al, 2022), Leishmanicidal activity against the promastigote forms of L. amazonensis (Callejon et al, 2014), anxiolytic and anti-depressant (Chu et al, 2019), bone protective effect in the tibia of ovariectomized rats (Xiao et al, 2021), antihepatotoxicity by reducing the levels of transaminases, ALP, bilirubin, and LDH to normal (Mujahid et al, 2017), retention of fear memory but did not prevent the extinction of fear memory (de Oliveira et al, 2014), Aurora kinase inhibitor (Hoang et al, 2016), antiplasmodial (Rukachaisirikul et al, 2007b;Waiganjo et al, 2020), inhibitor of neuronal nicotinic receptors (Setti-Perdigão et al, 2013).…”

Pharmacokinetic and metabolomic studies with a BIO 300 Oral Powder formulation in nonhuman primates

“…Genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one), one of the most abundant isoflavones, was thoroughly examined for its ability to mitigate radiation-induced cellular damage 24 and although its mechanism of action as a radioprotector is not fully understood, it has selective agonistic activity for estrogen receptor beta (ERβ) 25 , 26 . ERβ operates as a negative feedback mechanism by stimulating cell cycle checkpoints and suppressing cell growth 27 – 30 . Stimulation of ERβ by genistein has been shown to occur at nanomolar concentrations with an IC 50 of 8.4 nM.…”

Pharmacokinetic and metabolomic studies with a BIO 300 Oral Powder formulation in nonhuman primates

“…Genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one), one of the most abundant iso avones, was thoroughly examined for its ability to mitigate radiation-induced cellular damage 24 and although its mechanism of action as a radioprotector is not fully understood, it has selective agonistic activity for estrogen receptor beta (ERβ) 25,26 . ERβ operates as a negative feedback mechanism by stimulating cell cycle checkpoints and suppressing cell growth [27][28][29][30] . Stimulation of ERβ by genistein has been shown to occur at nanomolar concentrations with an IC 50 of 8.4 nM.…”