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. 2024 Feb 5;29(3):735.
doi: 10.3390/molecules29030735.

Enhancement of Female Rat Fertility via Ethanolic Extract from Nigella sativa L. (Black Cumin) Seeds Assessed via HPLC-ESI-MS/MS and Molecular Docking

Ahmed M Nagy  1 , Mohamed F Abdelhameed  2 , Asmaa S Abd Elkarim  3 , Tushar C Sarker  4 , Ahmed M Abd-ElGawad  5 , Abdelsamed I Elshamy  6 , Abdelmohsen M Hammam  1
Affiliations

Enhancement of Female Rat Fertility via Ethanolic Extract from Nigella sativa L. (Black Cumin) Seeds Assessed via HPLC-ESI-MS/MS and Molecular Docking

Ahmed M Nagy et al. Molecules. .

Abstract

The characteristic chemical composition of Nigella seeds is directly linked to their beneficial properties. This study aimed to investigate the phytochemical composition of Nigella sativa seeds using a 100% ethanolic extract using HPLC-ESI-MS/MS. Additionally, it explored the potential biological effects of the extract on female rat reproduction. Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estrogen (E2), and Progesterone (P4) hormone levels were also assessed, along with the morphological and histological effects of the extract on ovarian, oviductal, and uterine tissues. Molecular docking was performed to understand the extract's activity and its role in regulating female reproduction by assessing its binding affinity to hormonal receptors. Twenty metabolites, including alkaloids, saponins, terpenes, flavonoids, phenolic acids, and fatty acids, were found in the ethanolic extract of N. sativa seeds through the HPLC-ESI-MS/MS study. The N. sativa seed extract exhibited strong estrogenic and LH-like activities (p < 0.05) with weak FSH-like activity. Furthermore, it increased the serum levels of LH (p < 0.05), P4 hormones (p < 0.001), and E2 (p < 0.0001). Molecular docking results displayed a strong interaction with Erβ, LH, GnRH, and P4 receptors, respectively. Based on these findings, N. sativa seeds demonstrated hormone-like activities, suggesting their potential as a treatment for improving female fertility.

Keywords: E2 hormones; FSH; HPLC-ESI-MS/MS; LH; Nigella sativa; molecular docking.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Weight of the genitalia and the ovaries of rats showing (A,B) the FSH-like activity of N. sativa seeds. (C,D) The LH-like activity of N. sativa seeds. (E) Weight of the uterine tissue/g, showing the Estrogen-like activity of N. sativa seeds (mean ± SEM, ns non-significant, * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001).
Figure 2
Figure 2
Female immature rats. (A) Control -ve group treated with saline; the uterus is elongated and thin, and the ovaries are small and contain small numbers of follicles (the arrows). (B) Control FSH +ve group treated with 20 IU of PMSG. The uterine body and horns are wide in diameter and filled with large quantities of fluids, and the ovaries are large and contain large numbers of large follicles (the arrows). (C) Control LH +ve group treated with 20 IU of PMSG followed by 20 IU of hCG 3 days later. The uteri were short and contained a large amount of secretions. The ovaries contained numerous corpora lutea (the arrows). (D,E) The uterine body and horns in the N. sativa-treated group were short, large in diameter, and filled with uterine secretions. The ovaries contained a large number of corpora lutea (CLs) (the arrows).
Figure 3
Figure 3
Cross-sections of the ovarian, oviductal, and uterine tissues (magnification 40×) of (A1–A3) control –ve group. (B1–B3) Control +ve FSH-like activity (PMSG) showing different stages of follicular maturation and large number of mature follicles (arrow). (C1–C3) Control +ve LH-like activity (PMSG + LH) showing strong luteal activity in the ovaries (arrow), characterized by the presence of multiple adjacent well-developed CLs and potential endometrial activity (arrow), including an increase in endometrial epithelium height.
Figure 4
Figure 4
Cross-sections of the ovarian, oviductal, and uterine tissues (magnification 40× and 100×) revealed (A1–A3) FSH-like activity of N. sativa characterized by the presence of multiple active follicles at different developmental stages (arrow). (B1–B3) LH-like activity of N. sativa showing multiple CLs and progestational proliferation, characterized by columnar lining epithelium and folding of endometrial villi (arrow).
Figure 5
Figure 5
Ovariectomized female rats. (A) Control (–ve) group treated with saline. The uterus is thin and elongated. (B) Control (+ve) group treated with Folone® (E2). The uterus is short, thin, and filled with large amounts of fluid, showing estrogenic activity. (C) N. sativa-treated group. The uterus is short and filled with medium amounts of secretions, showing estrogenic activity. The arrows showing the difference of uterine thickness between the groups.
Figure 6
Figure 6
Cross-sections of the uterine tissues (magnification 40× and 100×) revealed the estrogenic activity of (A1,A2) control ovariectomized rats. (B1,B2) E2-like activity of Folone-injected group. showing strong uterine activity in the reference group, characterized by active endometrial hyperplasia and dilation of uterine glands (arrow). (C1,C2) E2-like activity of N. sativa-treated group showing good estrogenic activity, as evidenced by the presence of active endometrial hyperplasia (arrow).
Figure 7
Figure 7
Concentrations of the gonadotropins and steroidal hormones in the serum of rats. (A) FSH serum concentration (mIU/mL). (B) LH concentration (mIU/mL). (C) Estrogen (E2) concentration (pg/mL). (D) Progesterone (P4) concentration (pg/mL), (mean ± SEM, ns non-significant, * p ≤ 0.05, ** p ≤ 0.01,*** p ≤ 0.001, **** p ≤ 0.0001).
Figure 8
Figure 8
2D and 3D representations of (A,B) octadecadienoic acid with Estrogen β Receptor (ER β), (C,D) hederagenin pentoside with Human Gonadotropin-Releasing Hormone Receptor (GnRHR), (E,F) hymoquinol glucoside with Luteinizing Hormone receptor (LHR), and (G,H) magnoflorine with Progesterone Receptor (PR).
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