Sustainable valorization of Piennolo tomato leaves (Solanum lycopersicum L.) as a source of rutin: extraction optimization, antiglycation activity, and ex vivo skin distribution

Advanced glycation end products (AGEs) contribute to skin ageing and diabetes-related tissue dysfunction. This study investigated Piennolo tomato leaves ( Solanum lycopersicum L.), an underutilized agro-food by-product, as a source of rutin and antiglycation bioactives. Response surface methodology identified ethanol concentration and extraction time as significant variables for rutin recovery, whereas temperature showed no significant main effect within the tested range. Optimized food-grade extraction conditions (35% ethanol, 70.8 min) yielded 8.22 mg rutin/g DW, close to the predicted 8.45 mg/g DW. HPLC-DAD and HPLC-HESI-MS/MS profiling identified 24 phenolic compounds. The optimized Piennolo tomato leaf (OPTL) extract exhibited in vitro radical-scavenging activity in DPPH (IC₅₀ = 0.981 mg/mL; 95% CI 0.803–1.33) and ABTS (IC₅₀ = 1.36 mg/mL; 95% CI 1.23–1.52) assays and inhibited AGE formation (IC₅₀ = 3.62 mg/mL; 95% CI 2.53–5.36). Ex vivo Franz diffusion studies showed preferential cutaneous rutin retention, with receptor-phase detection only at 8 h.