In Vitro Activation of eNOS by Mangifera indica (Careless™) and Determination of an Effective Dosage in a Randomized, Double-Blind, Human Pilot Study on Microcirculation

Mangifera indica fruit preparation (Careless (TM)) activates the evolutionary conservedmetabolic sensors sirtuin 1 and adenosine monophosphate-activated protein kinase, which have been identified as playing a key role in microcirculation and endothelial function. Here, an acute effect of a single dose of 100 mg or 300 mg Careless (TM) on microcirculation was investigated in a randomized, double-blind, crossover pilot study in ten healthy women to determine the effective dosage. Microcirculation and endothelial function were assessed by the Oxygen-to-see system and pulse amplitude tonometry (EndoPAT (TM)), respectively. Cutaneous blood flow was increased over time by 100 mg (54% over pre-values, p = 0.0157) and 300mg (35% over pre-value, p = 0.209) Careless (TM). The EndoPAT (TM) reactive hyperemia response was slightly improved 3 h after intake compared to pretesting with 300 mg Careless (TM). Furthermore, activation of endothelial nitric oxide synthase, as an important regulator for endothelial function, was tested in vitro in primary human umbilical vein endothelial cells. Careless (TM), after simulation of digestion, increased the activated form of endothelial nitric oxide synthase dose-dependently by 23% (300 mu g/mL), 42% (1500 mu g/mL), and 60% (3000 mu g/mL) compared to the untreated control. In conclusion, the study suggests moderate beneficial effects of Careless (TM) on microcirculation, which is at least partly mediated by endothelial nitric oxide synthase activation.