Phytochemical Profiling and Assessment of Lannea Welwitschia in Mitigation of Cdcl2-Induced Biochemical and Reproductive Dysregulation: Modulatory Effects on Steroidogenic Enzymes (3β-Hsd, 17β-Hsd, Cyp19a1, Star) and in Vivo Mechanisms in Female Rats

Abstract

Ethnopharmacological relevanceCadmium chloride (CdCl2), a well-documented heavy metal pollutant, induces biochemical toxicity and reproductive dysfunction. Lannea welwitschii is valued for its nutrition and medicine, with edible fruits and bark used for women's ailments, diarrhea, and hemorrhoids.Aim of the studyThis study evaluated the protective effects of Lannea welwitschii ethanol extract against CdCl2-induced biochemical and reproductive impairments in female rats.Materials and methodsThe phytochemical profile of bark ethanol extract was analyzed using GC-MS. In vitro antioxidant and anti-inflammatory activities were assessed using spectrophotometry. Fifty female albino rats were divided into five groups (n=10). Reproductive toxicity was induced with 5 mg/kg b.w. CdCl2 for 21 days, followed by 21-day oral extract treatment. Group 1 (normal control) received distilled water, Group 2 (CdCl2 control) received 5 mg/kg b.w., Group 3 received 0.5 mg/kg b.w. Clomid, while Groups 4 and 5 received 200 and 400 mg/kg b.w. Lannea welwitschii extract, respectively. Ovaries were collected for biochemical and molecular analysis.ResultsGas chromatography-mass spectrometry (GC-MS) analysis identified 59 phytochemical constituents in the extract, including alkanes (23.58%), sesquiterpenoids (9.84%), fatty acids (9.33%), fatty acid esters (8.12%), and phenols (6.69%). The plant showed varying in vitro antioxidant and anti-inflammatory activities. For in vivo evaluations, Treatment with L. welwitschii extract significantly increased superoxide dismutase (SOD) and catalase (CAT) activities while reducing malondialdehyde (MDA), glutathione peroxidase (GPX), and reduced glutathione (GSH) levels. Total cholesterol (TCHOL) increased, whereas triglycerides (TG) decreased in treated groups compared to the CdCl2 group. Fecundity studies revealed an increase in litter size among L. welwitschii-treated groups, alongside enhanced testosterone levels and reduced estradiol levels. These effects correlated with the upregulation of key steroidogenic genes, including Steroidogenic Acute Regulatory Protein (stAR), 3β-Hydroxysteroid Dehydrogenase Type 2 (Hsd3β2), Cytochrome P450 Family 19 Subfamily A Member 1 (Cyp19A1), and 17β-Hydroxysteroid Dehydrogenase Type 1 (Hsd17β1). Histological analysis confirmed ovarian tissue regeneration.ConclusionThe results of this study suggest that Lannea welwitschii has fertility properties, possibly acting via modulation of reproductive genes.

Note:
Funding declaration: None.

Conflict of Interests: The authors report there are no competing interests to declare.

Ethical Approval: Before performing any experimental procedures, our ethics committee protocols were ethically approved by the institutional ethical committee, Faculty of Basic Medical Sciences, with approval No 282BCM3224.

Keywords: Cadmium chloride, Lannea welwitschii, reproductive dysfunction, Antioxidant activity, fertility