Mogale, TidimaloDe Beer, Andries DaniëlRudolph, Willem JohannesSteenkamp, Vanessa2026-03-162026-03-162026-04-06Mogale, T., De Beer, A.D., Rudolph, W.J. & Steenkamp, V. 2026, 'Catha edulis and Datura stramonium mitigate oxidative stress, mitochondrial dysfunction, and cell death in an SH-SY5Y model of Parkinson’s disease', Journal of Ethnopharmacology, vol. 360, art. 121223, pp. 1-17, doi : 10.1016/j.jep.2026.121223.0378-8741 (print)1872-7573 (online)10.1016/j.jep.2026.121223http://hdl.handle.net/2263/109010DATA AVAILABILITY : Data will be made available on request.INTRODUCTION : Parkinson's disease (PD), the second most common neurological disorder, is often managed with medications targeting specific symptoms. Complementing conventional therapies, medicinal plants are frequently used for neurological disorders, including PD. This study evaluated the effects of crude extracts and fractions of Catha edulis (Vahl) Forssk. ex Endl. and Datura stramonium L.—psychoactive plants—on PD-related mechanisms using SH-SY5Y human neuroblastoma cells. METHOD : Crude extracts of C. edulis (leaves) and D. stramonium (leaf/root mixture) were prepared using dichloromethane/methanol (50/50). Fractionation was performed via C8 solid-phase extraction. Cytotoxicity and cytoprotective effects of the crude extracts and fractions against 6-hydroxydopamine-induced cytotoxicity were assessed using the sulforhodamine B assay. Mechanistic studies included reactive oxygen species (ROS) generation, mitochondrial integrity, and apoptosis assays. In silico analysis was used to assess the binding of biomarkers to dopamine receptors. RESULTS : Both plant extracts exhibited minimal cytotoxicity. Crude extracts and fractions (F1–F7) displayed cytoprotective effects (5.8–34.28 %). The highest ROS reduction was observed for F1 of C. edulis (1.72-fold) and F2 of D. stramonium (1.33-fold). Both extracts reduced caspase 3/7 activation and maintained mitochondrial integrity. Atropine and scopolamine showed cytoprotection with IC50 values of 49.48 μM and 48.26 μM, respectively. In silico analysis indicated strong binding affinities of norephedrine and noradrenaline to dopamine D1 and D2 receptors. CONCLUSION : Both plant extracts preserved cell viability, reduced ROS levels, and maintained mitochondrial integrity, highlighting their potential as therapeutic agents for PD.en© 2026 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Parkinson's diseaseCatha edulisOxidative stressDatura stramoniumCytoprotectionArticle