The rising demand for alternative solutions to diabetes mellitus has prompted significant interest in the exploration of plant-derived anti-diabetic compounds, especially within a circular economy framework that seeks sustainable and profitable reuse options. In this context, red (RSGO) and white (WGSO) grape seed oils, by-products of Sicilian vineyards, were prepared, analyzed for their fatty acid, polyphenol, carotenoid, and chlorophyll content, and evaluated for their glucose-lowering ability on HepG2 cells. Utilizing cytochemical techniques, flow cytometry, and protein blotting, we explored the effects of non-toxic oil dilutions on (i) glycogen storage, (ii) glucose consumption/uptake, (iii) GLUT-2, GLUT-4, and hepatocyte nuclear factor-1α (HNF1α) expression levels, and (iv) AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), AKT, and PKCζ phosphorylation states, which are involved in insulin-mediated and -independent regulation of GLUT-4 membrane exposure. RGSO and WGSO, despite adopting slightly varying molecular strategies, were both proven to be effective stimulators of glucose absorption and glycogenesis. Specifically, RSGO promoted GLUT-2 and GLUT-4 up-regulation, whereas the WGSO-induced effect was associated with an increase in GLUT-4 levels alone. Moreover, the oils activated both pathways responsible for GLUT-4 translocation. Therefore, these wine-making residues have substantial potential as anti-diabetic solutions, holding promise for integration into the biomedical and food sectors.

The marine angiosperm Posidonia oceanica (Linnaeus) Delile, 1813 is a rich source of phytotherapeutic compounds whose potential applications for human health remain largely uninvestigated. Here, we determined the differential impact of aqueous extracts from P. oceanica’s green leaves (GLE) and rhizomes (RE) on the inflammation-related mRNA expressions and protein levels, nitric oxide (NO) release, and endocytic activity in LPS-stimulated RAW 264.7 macrophages. We also examined the influence of the extracts in modulating the activation of components of intracellular signaling pathways. Co-treatments of LPS-stimulated RAW 264.7 cells in the presence of either GLE or RE resulted in a reduction in NO production, associated with a down-regulation of Nos2 expression, reduced levels of COX-2 and TNFα proteins, and a decrease in Nfkb1 expression and NF-κB activation. No effect was exerted on the release of IL-6. Moreover, co-exposures to LPS and the extracts led to an elevation in pJNK and pAKT levels alongside a reduction in pERK. In contrast to GLE, RE specifically lowered IL-1β production, induced a more robust increase in IL-10, positively influenced the endocytic function of RAW 264.7 cells, and drastically up-regulated the phosphorylation of p38. The data obtained indicate that GLE and RE exhibit considerable promise as prospective anti-inflammatory and immunomodulatory agents.

Seed oils from Sicilian white (WGSO) and red grapes (RGSO) were examined for their possible cytotoxic effect on HepG2 liver and CaCo-2 colorectal cancer cells, the latter also induced to intestinal differentiation. Half maximal inhibitory dilution (ID₅₀) values were obtained from viability assays, excluding RGSO-treated HepG2 and differentiated CaCo-2 cells exposed to both oils, which were unresponsive. Cell morphology and cycle status, reactive oxygen species (ROS) production, and the levels of cytoprotection, regulated cell death (RCD), and autophagy markers were evaluated. No occurrence of canonical apoptosis was proven in any experimental condition. In HepG2 cells, WGSO ID₅₀ primarily triggered autophagy collapse, as evidenced by modulation of Beclin-1, p62 and LC3 markers, initiating a cascade of metabolic disturbances that led to oxidative stress reaction and mild inflammatory signaling. In CaCo-2 cells, WGSO ID₅₀ mainly elicited a strong ROS-mediated cell injury without major alterations in autophagy, with transient activation but incomplete execution of pyroptotic and necroptotic effectors (gasdermin-D, pMLKL and HMGB1). In the same cells, RGSO ID₅₀ induced a weaker metabolic perturbation with transient activation of multiple RCD pathways and concomitant autophagy inhibition. Research findings revealed distinct damage-inducing properties linked to oils’ chemical profiles, underscoring their prospective utilization as beneficial bioactive supplements.