Pawpaw (Asimina triloba) is a native North American fruit tree that has grown in popularity as an alternative medicine because of its anticancer potential. This cytotoxicity to cancer cells is attributed to bioactive compounds known as annonaceous acetogenins, secondary metabolites that inhibit complex I of the mitochondrial respiratory chain, inducing cell death. However, chronic consumption of Annonaceae species has also been linked to neurodegenerative diseases such as atypical parkinsonism. Considering geographical variation among secondary metabolite concentrations, pawpaw's large native range across the eastern United States could contribute to differences in bioactive compositions, causing unpredictable health effects. This study investigates the presence and variation of annonacin, a particularly cytotoxic acetogenin, among wild populations of pawpaw in the Mountains and Piedmont of North Carolina. Leaf samples were air dried, macerated with 80% methanol, concentrated using rotary evaporation, lyophilized, and analyzed by UHPLC. Annonacin was detected in all samples, with a mean annonacin concentration of 516.2 ± 238.4 mg/L and substantial variance among extracts. No statistically significant geographic trend was observed in this dataset, suggesting local environmental conditions and individual plant biological factors may play a more significant role in secondary metabolite production than broader geographic location alone. This was seen in the 2-3-fold differences within some locations. Characterizing variation in pawpaw secondary metabolites can support the advancement of pawpaw-derived therapeutics, as well as highlight the health risks associated with its unregulated consumption.
