Antioxidant and Anti-Inflammatory Activities of Buffalo Milk δ-Valerobetaine

delta-Valerobetaine (delta VB), a constitutive metabolite of ruminant milk, is produced in the rumen from free dietary N-epsilon- trimethyllysine occurring ubiquitously in vegetable kingdom. The biological role of delta VB is poorly known. Here, the anti-oxidant and anti-inflammatory potential of buffalo milk delta VB was tested in vitro during high-glucose (HG)-induced endothelial damage. Results indicated that delta VB (0.5 mM) ameliorated the HG cytotoxicity (0.57 +/- 0.02 vs 0.41 +/- 0.018 O.D. (P < 0.01). Interestingly, buffalo milk extracts enriched with delta VB showed improved significant efficacy in decreasing reactive oxygen species, lipid peroxidation, and cytokine release during HG treatment compared to milk extracts alone (P < 0.05). It is noteworthy that delta VB reduced the HG-activated inflammatory signal by modulating SIRT1 (0.96 +/- 0.05 vs 0.85 +/- 0.04 AU), SIRT6 (0.82 +/- 0.04 vs 0.61 +/- 0.03 AU), and NF-kappa B (0.85 +/- 0.03 vs 1.23 +/- 0.03 AU) (P < 0.05). On the whole, our data show the first evidence of delta VB efficacy in reducing endothelial oxidative stress and inflammation, suggesting a potential role of this betaine as a novel dietary compound with health-promoting properties.