Salvia macilenta Boiss extract: phytochemical analysis, nanoformulation in Eudragit-coated liposomes and evaluation of antioxidant/inflammatory response in vitro

This study presents the development and biological evaluation of an Eudragit-coated liposomal oral delivery system for an extract from Salvia macilenta Boiss. The phytochemical analysis of an extract from S. macilenta aerial parts, based on liquid chromatography-mass spectrometry, led to the isolation of a new rearranged nor-abietane diterpenoid, along with 31 known metabolites encompassing various classes, including flavonoids, phenolic compounds, and terpenes with known antioxidant/anti-inflammatory properties. The S. macilenta extract was incorporated into Eudragit-coated liposomes with a two-step process involving sonication and enteric polymer-coating. The Eudragit-coated liposomes exhibited an average diameter of 118 nm and a high entrapment efficiency of the extract's bioactive marker compounds: rosmarinic acid at 83.24 % and carnosol at 51.19 %. The Eudragit-coated liposomes showed excellent storage stability over three months and remained unaltered in simulated gastric and intestinal fluids. In vitro studies in LPS-stimulated HepG2 cells demonstrated that the Eudragit-coated liposomes significantly enhanced the extract's protective effect against oxidative stress and inflammation, as indicated by the upregulation of antioxidant proteins (SOD-2, NQO1, NRF-2) and the reduction of pro-inflammatory markers (NO, TNF-α, IL-1β, NF-κB, IL-6). Moreover, the Eu-liposomes achieved a 20-fold enhancement of the intracellular uptake of the extract's marker compounds (rosmarinic acid and carnosol), compared to the non-formulated extract. Overall, the findings of this study suggest that Eudragit-coated liposomes are a promising oral delivery system for boosting the bioavailability and bioactivity of S. macilenta extract, which could be exploited for nutraceutical purposes to restore oxInflammation balance.