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

Planta Med. 2016 Mar;82(4):298-304. doi: 10.1055/s-0035-1558219. Epub 2015 Nov 19.


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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Cells, Cultured
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Endothelium, Vascular / drug effects
  • Enzyme Activation
  • Female
  • Humans
  • Mangifera / chemistry*
  • Microcirculation / drug effects*
  • Middle Aged
  • Nitric Oxide Synthase Type III / metabolism*
  • Oxygen / blood
  • Pilot Projects


  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Oxygen