GC–MS Characterization, Brine Shrimp Lethality, and In Silico Toxicity Prediction of Alkaloid Fractions from the Stem Bark of Nauclea diderrichii

Introduction: Alkaloids remain an important source of bioactive compounds with therapeutic potential; however, the toxicological characterization of many ethnomedicinal plants remains limited. Nauclea diderrichii is widely utilized in West African traditional medicine for the management of various ailments, yet the toxicity profile of its alkaloid constituents is poorly understood. This study investigated the chemical composition, preliminary cytotoxicity, and predicted toxicological properties of alkaloid-rich fractions obtained from the stem bark of N. diderrichii using integrated analytical, biological, and computational approaches.

Methods: Alkaloid-rich fractions were obtained through solvent extraction and chromatographic separation of powdered stem bark material. Chemical profiling was performed using gas chromatography–mass spectrometry (GC–MS), and compounds were identified through comparison with mass spectral databases and retention index data. Preliminary toxicity screening was conducted using the Artemia salina brine shrimp lethality assay across graded concentrations of each fraction, with mortality assessed after 24 hours of exposure. Median lethal concentration (LC₅₀) values were estimated from dose–response relationships. Major identified compounds were further subjected to in silico toxicity prediction using ProTox-II to evaluate predicted acute toxicity and organ toxicity endpoints.

Results: GC–MS analysis revealed the presence of structurally diverse alkaloidal and heterocyclic constituents, including indole- and quinoline-related compounds, with compositional variability observed among fractions. Brine shrimp lethality assays demonstrated concentration-dependent toxicity, with selected fractions exhibiting moderate to high cytotoxic activity based on LC₅₀ values. In silico prediction suggested varying toxicity classes and organ toxicity liabilities for several major constituents, supporting the observed bioactivity patterns in the biological assay.

Conclusion: The combined GC–MS, brine shrimp lethality, and computational toxicity findings provide preliminary evidence that alkaloid fractions from N. diderrichii possess biologically active constituents with measurable toxicological effects. This integrated approach contributes baseline toxicological data for the plant and supports further mechanistic, pharmacological, and safety investigations of its alkaloid components.