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

Abstract

δ-Valerobetaine (δVB), a constitutive metabolite of ruminant milk, is produced in the rumen from free dietary Nε- trimethyllysine occurring ubiquitously in vegetable kingdom. The biological role of δVB is poorly known. Here, the antioxidant and anti-inflammatory potential of buffalo milk δVB was tested in vitro during high-glucose (HG)-induced endothelial damage. Results indicated that δVB (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 δVB 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 δVB 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-κB (0.85 ± 0.03 vs 1.23 ± 0.03 AU) (P < 0.05). On the whole, our data show the first evidence of δVB efficacy in reducing endothelial oxidative stress and inflammation, suggesting a potential role of this betaine as a novel dietary compound with health-promoting properties.

Synergistic Effect of Dietary Betaines on SIRT1-Mediated Apoptosis in Human Oral Squamous Cell Carcinoma Cal 27

“…It is tempting to speculate that pure betaines cause an increased metabolic oxidative burden which might directly/indirectly affect nuclear expression of SIRT1. Nevertheless, it is evident that milk, even at µM concentration of betaines, displays a more robust effect on SIRT1 and cell proliferation compared to single tested betaines (mM), probably due to the occurrence of other known bioactive molecules, including short-chain acylcarnitines and small peptides [6,9].…”

“…A growing body of evidence shows that betaines are important human nutrients that participate in the methionine cycle acting as methyl donors. Compounds belonging to this class, such as glycine betaine, stachydrine, ergothioneine, γ-butyrobetaine (γBB), and δ-valerobetaine (δVB) show protective effects against cardiovascular disease and cancer [3][4][5][6][7][8].…”

“…δVB (N,N,N-trimethyl-5-aminovaleric acid) is produced by rumen microbiota from the transformation of N ε -trimethyllysine and is likely degraded by the intestinal host microbiota via γ-butyrobetaine hydroxylase enzyme, thus suggesting a possible metabolic connection between δVB and γBB [9,10]. In vitro biological activities of δVB include inhibition of β-oxidation of fatty acids in mice cardiomyocytes, anti-inflammatory effects in endothelia damaged by hyperglycemia, and cytotoxic effects in human colon adenocarcinoma cells [6,8,12]. In vivo and clinical evidence indicate that δVB inversely correlates with metabolic syndrome markers after the intake of whole grain-rich diets [13,14].…”

“…The present study aimed at evaluating the possible anticancer effects of milk betaines in oral squamous cell carcinomas [25]. In particular, in light of recent evidence showing that pure δVB displays more pronounced health-promoting properties when in combination with other milk components [6,8], particular emphasis was placed on the evaluation of its possible synergistic/additive effects with γBB, given the remarkable structural resemblance of these two betaines.…”

Changes in Bull Semen Metabolome in Relation to Cryopreservation and Fertility

“…Among the two putatively identified metabolites, glycine betaine is of particular interest. Glycine betaine is a methyl group donor that functions in the normal metabolic cycle of methionine-transforming the harmful homocysteine into methionine [31]-modulates cellular responses to osmotic stress [32], acts as an osmolyte and cryoprotectant [33] and exerts antioxidant and anti-inflammatory actions [34,35]. It has been reported that betaine improves the quality of cryopreserved spermatozoa in ram [36,37] and stallions [38,39].…”