Modulatory effects of lannea welwitschia on cadmium-induced reproductive and biochemical dysregulation via steroidogenic enzyme regulation in female rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cadmium chloride (CdCl2) is a common environmental pollutant that impairs female reproductive health via oxidative stress and hormonal disruption. Lannea welwitschii (Anacardiaceae), used in West African traditional medicine for infertility, diarrhoea, and haemorrhoids, has not been scientifically evaluated for its protective effects against heavy metal-induced reproductive damage.

AIM OF THE STUDY: To investigate the protective and fertility-enhancing effects of the ethanol extract of Lanneawelwitschii bark on CdCl2-induced reproductive and biochemical alterations in female albino rats.

MATERIALS AND METHODS: The ethanol extract of Lannea welwitschii (L. welwitschii) bark was subjected to phytochemical analysis using gas chromatography-mass spectrometry (GC-MS). Antioxidant capacity was evaluated in vitro using DPPH radical scavenging, nitric oxide scavenging, FRAP and H2O2 inhibition assays. Thirty-five female rats (130-160 g) were assigned to 5 groups (n = 7). Reproductive toxicity was induced in all but the control group using oral administration of cadmium chloride (CdCl2, 5 mg/kg body weight) for 21 consecutive days. Thereafter, rats were orally treated with L. welwitschii extract at doses of 200 or 400 mg/kg body weight for another 21 days. Clomiphene citrate (0.5 mg/kg) served as the positive control. At the end of treatment, serum and ovarian tissues were collected for biochemical analysis. Ovarian histopathology was also examined.

RESULTS: Gas Chromatography-Mass Spectrometry (GC-MS) analysis identified 59 phytoconstituents in the ethanol bark extract of L. welwitschii, accounting for 81.78 % of the total chromatographic area, with major classes including alkanes (23.58 %), sesquiterpenoids (9.84 %), fatty acids (9.33 %), and phenols (6.69 %). The extract exhibited concentration-dependent antioxidant activity, showing DPPH scavenging rates comparable to BHT at 40 mg/mL (p < 0.05) and superior H2O2 scavenging relative to gallic acid at 50 mg/mL. The FRAP assay revealed a significant increase (p < 0.05) in ferric-reducing power at 80 mg/mL, while nitric oxide inhibition peaked at 40 mg/mL. In anti-inflammatory assays, the extract significantly inhibited albumin denaturation and heat-induced haemolysis at 40 mg/mL (p < 0.05), matching aspirin's effect. In vivo, rats exposed to CdCl2 and treated with 200-400 mg/kg extract showed significant (p < 0.05) increases in SOD and CAT activities, reductions in MDA, IL-6 and TNF-α levels, and normalisation of serum testosterone and estradiol levels compared to CdCl2 controls. Histological examination revealed marked restoration of ovarian morphology and corpora lutea formation, consistent with improved fecundity and almost 100 % fertility in the 400 mg/kg group.

CONCLUSION: Lannea welwitschii bark extract protects against CdCl2-induced female reproductive toxicity by modulating oxidative stress, restoring hormonal balance, and regulating steroidogenesis-related genes, thereby supporting its traditional use and potential therapeutic value for female infertility associated with environmental toxins.