UHPLC-MS/MS profiling of Aplysia depilans and assessment of its potential therapeutic use: Interference on iNOS expression in LPS-stimulated RAW 264.7 macrophages and caspase-mediated pro-apoptotic effect on SH-SY5Y cells

Aplysia sea hares are harmless to humans and good materials for producing compounds with pharmacological properties. Aplysia species have been investigated for their human nutritional value. The knowledge on the metabolic machinery from edible Aplysia depilans Gmelin is herein broadened by identifying chlorophylls, phenolic acids, terpenes, including xanthophylls, and alkaloids, some being reported for the first time both in the species and genus. The anti-inflammatory potential was assessed using RAW 264.7 macrophages challenged with lipopolysaccharide, revealing that A. depilans ethyl acetate partionated fraction interfered with cellular NO levels, mainly due to a decrease on inducible nitric oxide synthase expression. A strong capacity to inhibit phospholipase A2 and 5-lipoxygenase was also evidenced. Morphological studies with SH-SY5Y neuroblastoma cells demonstrated chromatin condensation compatible with apoptosis, confirmed by the activation of caspase 3/7. The anti-inflammatory and pro-apoptotic effects reinforce A. depilans as an interesting ingredient to be included on the formulation of smart foods and/or nutraceuticals.