Modulatory properties of Thespesia garckeana (F. Hoffm.) Exell & Hillc. Aqueous fruit extract on female rats reproductive hormones and tissues histology and potential inhibitory activity of its constituents against SRD5α2
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Date
2023
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Elsevier
Abstract
Ethnopharmacological relevance: Thespesia garckeana (F. Hoffm.) Exell & Hillc. is called Gorontula (Kola of Tula) in
Nigeria, Morojwa in Bostwana, and Thespesia garckeana in South Africa and is widely distributed across Africa. Its
parts reportedly possess multiple medicinal properties and are employed for treating various diseases. In Tula,
Gombe State, Nigeria, the ripe fruit decoction is taken as remedy for female infertility as documented by
Ochokwu and co in the Journal of Biology, Agriculture and Healthcare in 2015.
Aim of the study: This research examined the effects of aqueous fruit extract of T. garckeana (F. Hoffm.) Exell &
Hillc. (AFETG) on selected reproductive tissues and hormones in female rats and also evaluated the inhibitory
potentials of its phytoconstituents against human 5-alpha reductase 2 (SRD5α2) using in silico approach.
Methods: Twenty-five (25) sexually matured female rats were randomized into 5 groups (i.e. A - E). Oestrous in
the rats was synchronized (subcutaneous oestradiol conjugate [10 μg/100 g BW]). Group A received distilled
water (control). Group B received standard drug, clomiphene citrate (0.85 mg/kg BW), while groups C, D, and E
received AFETG at 50, 100, and 200 mg/kg BW respectively. The animals were treated for five (5) days and
sacrificed 24 h after. Their blood was collected and prepared for analysis of serum prolactin, oestradiol (E2),
follicle-stimulating hormone (FSH), and luteinizing hormone (LH) while ovaries, uteruses, and oviducts were
studied for histological and histomorphometric changes. For the in silico study, the target protein, human steroid
5α-reductase 2 (SRD5α2) was prepared and its receptor grid was generated using Optimized Potential for Liquid
Simulations-2005. The ligand 2D structures were prepared using LigPrep 2.4 software and docked using Glide.
The binding energy of the ligands to the protein receptor was predicted using Molecular Mechanics/Generalized
Born Surface Area (MM-GBSA) analysis.
Results: AFETG significantly increased serum levels of E2 but did not alter serum levels of prolactin, LH and FSH
when compared with distilled water and clomiphene citrate. AFETG also significantly increased ovarian tertiary
follicular diameter, oviductal epithelial height and serosa thickness as well as uterine endometrial epithelial
height, endometrial thickness, and myometrial thickness when compared with control. Ovarian secondary
follicular diameter and oviductal submucosa thickness and muscular thickness were significantly decreased by
AFETG when compared with control. Two compounds in T. garckeana (F. Hoffm.) Exell & Hillc.; D-Melezitose (− 12.55 kcal/mol XP GScore) and 1, 3, 4-trihydroxy-5-oxo cyclohexane-1-carboxylic acid (− 9.136 kcal/mol XP
GScore) exhibited higher binding affinities for SRD5α2 than the reference ligand, epristeride (− 8.096 kcal/mol
XP GScore).
In conclusion, the ability of AFETG to increase serum E2 level, thickness of uterine endometrium and ovarian
tertiary follicles size can be explored for the treatment of female infertility caused by thinning of the uterine
endometrium and reduced follicular size. Two compounds in AFETG (i.e. D-Melezitose and 1, 3, 4-trihydroxy-5-
oxo cyclohexane-1-carboxylic acid are potential inhibitors of SRD5α2, thus aiding the biosynthesis of E2.
Available evidence therefore corroborate the traditional use of T. garckeana (F. Hoffm.) Exell & Hillc fruit as a
female fertility enhancer in Northern Nigeria.
Description
Keywords
Rats, Ovary, molecular docking simulation, clomiphene, SOCIAL SCIENCES::Statistics, computer and systems science, Thespesia garckeana