title: 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.
abstract: Mangifera indica fruit preparation (Careless™) activates the evolutionary conserved metabolic 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™ 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™), respectively. Cutaneous blood flow was increased over time by 100 mg (54% over pre-values, p = 0.0157) and 300 mg (35% over pre-value, p = 0.209) Careless™. The EndoPAT™ reactive hyperemia response was slightly improved 3 h after intake compared to pretesting with 300 mg Careless™. 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™, after simulation of digestion, increased the activated form of endothelial nitric oxide synthase dose-dependently by 23% (300 µg/mL), 42% (1500 µg/mL), and 60% (3000 µg/mL) compared to the untreated control. In conclusion, the study suggests moderate beneficial effects of Careless™ on microcirculation, which is at least partly mediated by endothelial nitric oxide synthase activation.
authors.affiliation: Vital Solutions Swiss AG, Romanshorn, Schweiz.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gerstgrasser
authors.affiliation: Vital Solutions Swiss AG, Romanshorn, Schweiz.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Röchter
authors.affiliation: BioTeSys GmbH, Esslingen.
authors.forename: Dirk
authors.initials: D
authors.lastname: Dressler
authors.affiliation: BioTeSys GmbH, Esslingen.
authors.forename: Christiane
authors.initials: C
authors.lastname: Schön
authors.affiliation: BioTeSys GmbH, Esslingen.
authors.forename: Claudia
authors.initials: C
authors.lastname: Reule
authors.affiliation: Vital Solutions Swiss AG, Romanshorn, Schweiz.
authors.forename: Sybille
authors.initials: S
authors.lastname: Buchwald-Werner
mesh_terms: D002478:Cells, Cultured; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D031022:Mangifera / Q000737:chemistry*; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D010865:Pilot Projects
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen