Anti-lipotoxic alkaloids from the roots of Polyalthia cerasoides

Driven by the ethnomedicinal use of Polyalthia cerasoides (Roxb.) Bedd. for liver disorders and the urgent need for novel therapies against metabolic dysfunction-associated steatotic liver disease (MASLD), a phytochemical study of its roots was undertaken. This investigation resulted in the identification of twenty-nine alkaloids, including five previously unreported, rare pyridocoumarin alkaloids (1-5) and an undescribed 8-oxoberberine alkaloid (11). The structures of undescribed compounds were established through extensive NMR and MS data analysis. Isolates were evaluated for their anti-lipotoxic effects and ability to ameliorate lipid accumulation in a palmitic acid (PA)-induced model of MASLD using hepatocytes. Several alkaloids, notably compounds 3 and 24 (a known bis-aporphine), demonstrated significant protective effects. They concomitantly mitigated lipid overload and PA-induced apoptosis, showcasing their multi-faceted hepatoprotective potential. Our findings substantiate the ethnopharmacological value of P. cerasoides and highlight its alkaloids, particularly 3 and 24, as valuable scaffolds for the discovery of anti-MASLD agents.