The Aqueous Extract of Dacryodes edulis (Burseraceae) Leaves Inhibits Cell Proliferation Induced by Estradiol on the Uterus and Vagina of Ovariectomized Female Wistar Rats

Abstract

Proliferation is a cellular process strongly linked to the genesis of cancer. Natural substances with antiproliferative activities are currently potential alternatives in the treatment of cancers. Dacryodes edulis, for instance, is a medicinal plant traditionally used in the treatment of cancer. Scientific studies have reported the antioxidant activity of this plant. In addition, the presence of prostate cancer chemopreventive polyphenols was reported in D. edulis extracts. Therefore, this study was aimed to evaluate the effects of the aqueous extract of D. edulis leaves on cell proliferation induced by estradiol in ovariectomized female Wistar rats. In this regard, ovariectomized (OVX) rats were cotreated with estradiol valerate (E₂V) (0.75 mg/kg) and the aqueous extract of D. edulis leaves. Control groups received either the vehicle (sham-operated animals and the OVX control), E₂V (0.75 mg/kg) only, or E₂V (0.75 mg/kg) and tamoxifen (10 mg/kg). Treatments were administered orally for 3 consecutive days, and animals were sacrificed thereafter. Epithelial heights of the uterus and vagina were assessed. Uterine levels of total cholesterol and estradiol were determined as well. Results showed that the aqueous extract of D. edulis leaves reversed the effects of estradiol as it reduced uterine weight (p < 0.05), uterine (p < 0.05), and vaginal (p < 0.001) epithelium heights. This antiproliferative effect of D. edulis was associated with reduced tissue (uterine) levels of estradiol (p < 0.001). These results suggest that the aqueous extract of D. edulis leaves could be a potential alternative treatment for proliferation-related diseases.

Figure 1

Quantitative analysis of phytochemical constituents of the leaves of D. edulis. GAE: gallic acid equivalent; QE: quercetin equivalent; E: extract.

Figure 2

Effects of treatments on the relative uterine wet weight. SHAM: sham-operated animals; OVX: ovariectomized animals; E₂V: estradiol valerate; TAM: tamoxifen; AE: aqueous extract of D. edulis leaves. Data are presented as mean ± S.E.M. (n = 6). ^∗p < 0.05 and ^∗∗∗p < 0.001 compared with SHAM; ^#p < 0.05, ^##p < 0.01, and ^###p < 0.001 compared with OVX; and ^ap < 0.05, ^bp < 0.01, and ^cp < 0.001 compared with OVX + E₂V.

Figure 3

Microphotographs (H&E 400x) (a) and epithelial height (b) of the uterus after 3 days of treatment. SHAM: sham-operated animals; OVX: ovariectomized animals; E₂V: estradiol valerate; TAM: tamoxifen; AE: aqueous extract of D. edulis leaves. Data are presented as mean ± S.E.M. (n = 6). ^∗∗p < 0.01 and ^∗∗∗p < 0.001 compared with SHAM; ^#p < 0.05 and ^##p < 0.01 compared with OVX; and ^ap < 0.05 compared with OVX + E₂V. LU: lumen; E epithelium.

Figure 4

Effects of treatments on uterine levels of total cholesterol (a) and estradiol (b). SHAM: sham-operated animals; OVX: ovariectomized animals; E₂V: estradiol valerate; TAM: tamoxifen; AE: aqueous extract of D. edulis leaves. Data are presented as mean ± S.E.M. (n = 6). ^∗∗p < 0.01 and ^∗∗∗p < 0.001 compared with SHAM; ^##p < 0.01 and ^###p < 0.001 compared with OVX; and ^bp < 0.01 and ^cp < 0.001 compared with OVX + E₂V.

Figure 5

Microphotographs (H&E 400x) (a) and epithelial height (b) of the vagina after 3 days of treatment. SHAM: sham-operated animals; OVX: ovariectomized animals; E₂V: estradiol valerate; TAM: tamoxifen; AE: aqueous extract of D. edulis leaves. Data from Figure 5(b) are presented as mean ± S.E.M. (n = 6). ^∗∗∗p < 0.001 compared with SHAM; ^###p < 0.001 compared with OVX; and ^Cp < 0.001 compared with OVX + E₂V. Lu: lumen; G: stratum germinativum; Gr: stratum granulosum; C: stratum corneum.