Steatosis is characterized primarily by excessive lipid accumulation in the form of triglycerides in the liver. Although resveratrol shows a low bioavailability, it has significant positive effects on steatosis. The aim of this study was to analyze whether some phase II and microbial resveratrol metabolites (trans-resveratrol-4′-O-glucuronide (R-4G); trans-resveratrol-3-O-glucuronide (R-3G); trans-resveratrol-3-O-sulfate (R-S) and dihydro-resveratrol (DH-R) were effective in reducing hepatocyte fat accumulation. An in vitro model mimicking the hepatocyte situation in fatty liver was developed by incubating mouse AML12 hepatocytes with palmitic acid (PA). For cell treatments, hepatocytes were incubated with 1, 10, or 25 µM resveratrol or its metabolites. Triglycerides and cell viability were assessed using commercial kits. Protein expression of enzymes and transporters involved in triglyceride metabolism were analyzed by western blot. We show for the first time that resveratrol and all the tested metabolites, at 1 µM, partially prevented lipid accumulation induced by the saturated fatty acid PA in AML12 hepatocytes. This effect was mainly due to the inhibition of de novo lipogenesis. This demonstrates that the low bioavailability of resveratrol is not as big a problem as it was thought to be, because resveratrol metabolites contribute to the delipidating effects of the parent compound.

Background: Inflammatory bowel disease is a complex intestinal inflammatory disorder linked to immune dysregulation, oxidative stress, and an imbalance in the gut microbiota. Grape seed flour (GSF), a winemaking by-product rich in polyphenols and fibres, displays antioxidant and anti-inflammatory properties and may help maintain gut homeostasis. Methods: The phenolic composition and antioxidant capacity of our GSF were evaluated. We assessed whether a diet containing 10% (w/w) GSF protects against dextran sulphate sodium (DSS)-induced acute colitis in BALB/c mice. Animals received either a standard diet or a GSF-supplemented diet before and during DSS exposure. Body weight and disease activity index were monitored. At sacrifice, colon length and colonic histology scoring were measured. The study of the faecal microbiota and predicted genome was performed using PICRUSt. Caecal metabolites, including short-chain fatty acids, were also quantified. Results: GSF is rich in fibres (64%) and exhibits a very high polyphenolic content and high antioxidant capacity. GSF supplementation attenuated DSS-induced weight loss and disease activity and limited colonic shortening and histological damage. It also improved biomarkers of colon, mesenteric lymph nodes (MLNs), and liver injury. At the molecular level, GSF downregulated key pro-inflammatory mediators in the colon and liver, while enhancing anti-inflammatory (e.g., IL-10) and antioxidant markers, indicating reinforcement of regulatory and redox-protective pathways along the gut–liver axis. At the gut microbiota level, GSF supplementation modulated α-diversity. Further analysis demonstrated that GSF reshaped the GM profile by preventing the blooming of some taxa, including UBA1819, Akkermansia, and Bacteroides caecimuris, and enriching butyrate-producing bacteria, such as Muribaculaceae and Ruminococcus. These shifts were accompanied by lower acetone and ethyl acetate levels and higher indole levels, which are known to support epithelial barrier integrity and mucosal homeostasis. Conclusions: Overall, GSF mitigates DSS-induced colitis through combined actions on inflammatory signalling, oxidative stress, immune regulation, microbiota composition and microbiota-derived metabolites, supporting its potential as a functional prebiotic ingredient for intestinal health.

Hibiscus plant cell cultures were developed to produce a cosmetic ingredient with anti-ageing properties. UHPLC-DAD-MS analysis of Hibiscus plant cell cultures revealed a high content of polyphenols, particularly hydroxycinnamic acid derivatives, including caffeoyl and p-coumaroyl conjugates. The biological activity of a 50/50 mixture of extracts from Hibiscus syriacus and Hibiscus rosa-sinensis cells was investigated in a human keratinocyte/fibroblast co-culture model, which better reproduces the reciprocal epithelial–mesenchymal interactions between epidermal keratinocytes and dermal fibroblasts than monocultures, using quantitative data-independent acquisition (DIA) LC-MS/MS proteomics combined with functional enrichment and protein–protein interaction analyses. A total of 7062 proteins were identified, of which 280 were differentially expressed (107 upregulated and 171 downregulated) following hibiscus treatment. The proteomic profile suggested coordinated molecular reprogramming associated with extracellular matrix remodelling, tissue repair, hydration, and attenuation of inflammatory signalling. Functional enrichment analysis revealed coordinated modulation of extracellular matrix organization, glycosaminoglycan metabolism, lysosomal function, cell communication, and inflammatory signalling. Upregulation of extracellular matrix and adhesion proteins, including lumican, collagen VIII, fibulin-5, syndecans, and glypicans, suggested coordinated extracellular matrix remodelling that may promote skin firmness and elasticity, while the downregulation of inflammatory regulators, including CARD16 and S100 family proteins, suggested attenuation of innate inflammatory responses. Overall, these findings provide mechanistic insights into the biological activity of Hibiscus cell culture extracts and support their potential as cosmetic ingredients promoting skin homeostasis and healthy skin ageing.