Acute Oral Toxicity of an Alkaloid-Rich Fraction of Nauclea diderrichii Stem Bark in Wistar Rats: Biochemical and Histopathological Evaluation

Abstract

The study evaluated the acute oral toxicity of an alkaloid-rich fraction derived from the stem bark of Nauclea diderrichii, a plant traditionally used in Sub-Saharan Africa for various ailments including malaria and gastrointestinal disorders. Acute oral toxicity was assessed in Wistar rats using Lorke’s method (Phase I: n = 3 per group; Phase II: n = 1 per dose). A separate cohort of male Wistar rats (n = 3 per group: vehicle control, 1000, 3000 and 5000 mg/kg) was used to evaluate body weight, relative organ weight, serum biochemical biomarkers and histopathology. No mortality was recorded at any dose up to 5000 mg/kg, indicating an oral LD₅₀ greater than 5000 mg/kg. Minor, transient behavioural changes such as lethargy and reduced feeding were observed at higher doses and resolved within 24 h. Body-weight gain was modestly reduced, and relative liver and kidney weights were significantly elevated at 3000 and 5000 mg/kg. Serum ALT, AST, ALP, bilirubin, urea, creatinine and cystatin C increased in a dose-dependent manner at these doses, while histopathological evaluation revealed no structural lesions in liver or kidney at any dose. The absence of mortality up to 5000 mg/kg suggests low acute lethality; however, the dose-dependent biochemical and organ-weight changes observed at higher doses indicate biological effects that warrant further investigation. The findings of this study served as the foundation of safety guide of traditional preparations of N. diderrichii and further sub-acute/chronic studies incorporating sensitive structural biomarkers are needed before therapeutic or ethnomedicinal safety conclusions can be drawn.