Mechanisms of cellular responses of the natural alkaloid caulerpin and its similarities with the lipid-lowering agent fenofibrate in Mytilus galloprovincialis

Marine-derived natural products have attracted increasing attention due to their promising pharmacological potential against various diseases. The present study investigated the hypolipidemic properties of the alkaloid caulerpin, a secondary metabolite of green algae of the genus Caulerpa, through an ex vivo approach with Precision-Cut Tissue Slices (PCTSs) of Mytilus galloprovincialis digestive glands. PCTSs were exposed to caulerpin (CAU) (100 µM) and fenofibrate (FFB) (100 µM) for 24, 48, and 72 h. Analyses of molecular and cellular responses pertaining to lipid metabolism suggested a similar mechanism of action between CAU and FFB in marine invertebrate species, resulting in a decrease in neutral lipid content ranging from 50 to 70%. CAU’s hypolipidemic action was not associated with increased prooxidant conditions, and slower metabolism of the natural alkaloid compared to FFB was indicated by the response of biotransformation and excretion pathways. Overall, these findings provide initial insights into the potential valorization of CAU for pharmaceutical and nutraceutical applications, highlighting the need for further investigation into its mechanisms of action, possible side effects, and interactions with other drugs.