Pitaya (Hylocereus lemairei) extracts avoid mitochondrial dysfunction and NF-k/NLRP-3-mediated inflammation in endothelial cells under high glucose and are in vivo safe

Background: Pitaya has gained popularity as a dietary alternative for diabetics. However, the precise molecular basis and biochemical effects are not well understood. This study aimed to evaluate pitaya influence in endothelial cells under high glucose, mimicking hyperglycemia. Methods: EA.hy926 cells were treated with 1 mu g/mL of extract for 24 h with 35 mM of glucose (HG) and/or metformin (MET; 0.5 mM). It was analyzed cell viability/proliferation, apoptosis, Delta psi m, and pHi. Markers of aerobic (NADH and succinate dehydrogenase, and ATP synthase) and anaerobic (LDH) glycolysis were evaluated, as well as NO levels, NF-k beta, and NLRP3 expressions. To determine in vivo safety, acute toxicity in A. salina was conducted (0.5-65 mg/mL). Chemical characterization was performed by HPLC. Results: HG negatively impacted cell viability and proliferation. Cells presented high levels of extracellular LDH and NO, as well as an increment on NADH, and succinate dehydrogenase activities, and ATP production. Cytometry revealed an increase in ROS levels, apoptosis, and changes in pHi and Delta psi m, accompanied by an increase in NF-k beta, and NLRP3 expressions. These alterations were partially (extract per se pulp and/or associated with MET) or totally (extract per se peel and/or MET associated) reversed. No toxicity for peel extract at concentrations until 65 mg/mL was found. HPLC revealed quercetin and kaempferol in both extracts. Conclusion: Data indicate that pitaya peel extract is safe and, according to a Principal Component Analysis, can be used as a co-therapeutic strategy to minimize oxidative damage and inflammation in endothelial cells under high glucose.