Planta Med 2016; 82(04): 298-304
DOI: 10.1055/s-0035-1558219
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

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

Alexandra Gerstgrasser
1   Vital Solutions Swiss AG, Romanshorn, Schweiz
,
Sigrid Röchter
1   Vital Solutions Swiss AG, Romanshorn, Schweiz
,
Dirk Dressler
2   BioTeSys GmbH, Esslingen
,
Christiane Schön
2   BioTeSys GmbH, Esslingen
,
Claudia Reule
2   BioTeSys GmbH, Esslingen
,
Sybille Buchwald-Werner
1   Vital Solutions Swiss AG, Romanshorn, Schweiz
› Author Affiliations
Further Information

Publication History

received 02 September 2015
revised 09 October 2015

accepted 12 October 2015

Publication Date:
19 November 2015 (online)

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.

 
  • References

  • 1 Selles AJ, Villa DG, Rastrelli L. Mango polyphenols and its protective effects on diseases associated to oxidative stress. Curr Pharm Biotechnol 2015; 16: 272-280
  • 2 Röchter S, Ehrhardt C, Buchwald-Werner S, Berger-Büter K, Schatton E. Benefits of a Mangifera indica L. fruit powder for well-aging – In vitro investigation of effects on master regulators for the aging process. Agro Food Ind Hi Tech 2015; 26: 4-7
  • 3 Zhang BB, Zhou G, Li C. AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab 2009; 9: 407-416
  • 4 Nogueiras R, Habegger KM, Chaudhary N, Finan B, Banks AS, Dietrich MO, Horvath TL, Sinclair DA, Pfluger PT, Tschop MH. Sirtuin 1 and sirtuin 3: physiological modulators of metabolism. Physiol Rev 2012; 92: 1479-1514
  • 5 Canto C, Auwerx J. PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol 2009; 20: 98-105
  • 6 Fisslthaler B, Fleming I. Activation and signaling by the AMP-activated protein kinase in endothelial cells. Circ Res 2009; 105: 114-127
  • 7 Muniyappa R, Montagnani M, Koh KK, Quon MJ. Cardiovascular actions of insulin. Endocr Rev 2007; 28: 463-491
  • 8 Ogden CL, Carroll MD, Flegal KM. Prevalence of obesity in the United States. JAMA 2014; 312: 189-190
  • 9 Muris DM, Houben AJ, Schram MT, Stehouwer CD. Microvascular dysfunction: an emerging pathway in the pathogenesis of obesity-related insulin resistance. Rev Endocr Metab Disord 2013; 14: 29-38
  • 10 Liu H, Wu B, Pan G, He L, Li Z, Fan M, Jian L, Chen M, Wang K, Huang C. Metabolism and pharmacokinetics of mangiferin in conventional rats, pseudo-germ-free rats, and streptozotocin-induced diabetic rats. Drug Metab Dispos 2012; 40: 2109-2118
  • 11 Forst T, Hohberg C, Tarakci E, Forst S, Kann P, Pfutzner A. Reliability of lightguide spectrophotometry (O2 C) for the investigation of skin tissue microvascular blood flow and tissue oxygen supply in diabetic and nondiabetic subjects. J Diabetes Sci Technol 2008; 2: 1151-1156
  • 12 Rossi M, Carpi A, Galetta F, Franzoni F, Santoro G. Skin vasomotion investigation: a useful tool for clinical evaluation of microvascular endothelial function?. Biomed Pharmacother 2008; 62: 541-545
  • 13 Gates PE, Strain WD, Shore AC. Human endothelial function and microvascular ageing. Exp Physiol 2009; 94: 311-316
  • 14 Wiernsperger N, Nivoit P, Bouskela E. Microcirculation in obesity: an unexplored domain. An Acad Bras Cienc 2007; 79: 617-638
  • 15 Ghanzanfari M, Vogt L, Banzer W, Rhodius U. Reproduzierbarkeit nicht-invasiver Durchblutungsmessung mit der Laser-Doppler-Spektroskopie. Phys Rehab Kur Med 2002; 12: 330-336
  • 16 Heinrich U, Moore CE, De Spirt S, Tronnier H, Stahl W. Green tea polyphenols provide photoprotection, increase microcirculation, and modulate skin properties of women. J Nutr 2011; 141: 1202-1208
  • 17 Neukam K, Stahl W, Tronnier H, Sies H, Heinrich U. Consumption of flavanol-rich cocoa acutely increases microcirculation in human skin. Eur J Nutr 2007; 46: 53-56
  • 18 Jiang DJ, Dai Z, Li YJ. Pharmacological effects of xanthones as cardiovascular protective agents. Cardiovasc Drug Rev 2004; 22: 91-102
  • 19 Ko FN, Lin CN, Liou SS, Huang TF, Teng CM. Vasorelaxation of rat thoracic aorta caused by norathyriol isolated from Gentianaceae. Eur J Pharmacol 1991; 192: 133-139
  • 20 Ugusman A, Zakaria Z, Chua KH, Nordin NA, Abdullah Mahdy Z. Role of rutin on nitric oxide synthesis in human umbilical vein endothelial cells. ScientificWorldJournal 2014; 2014: 169370
  • 21 Fusi F, Saponara S, Pessina F, Gorelli B, Sgaragli G. Effects of quercetin and rutin on vascular preparations: a comparison between mechanical and electrophysiological phenomena. Eur J Nutr 2003; 42: 10-17
  • 22 Liu H, Wang K, Tang Y, Sun Z, Jian L, Li Z, Wu B, Huang C. Structure elucidation of in vivo and in vitro metabolites of mangiferin. J Pharm Biomed Anal 2011; 55: 1075-1082
  • 23 Hodgson JM, Burke V, Puddey IB. Acute effects of tea on fasting and postprandial vascular function and blood pressure in humans. J Hypertens 2005; 23: 47-54
  • 24 Schmitt CA, Dirsch VM. Modulation of endothelial nitric oxide by plant-derived products. Nitric Oxide 2009; 21: 77-91
  • 25 Glahn RP, Lee OA, Yeung A, Goldman MI, Miller DD. Caco-2 cell ferritin formation predicts nonradiolabeled food iron availability in an in vitro digestion/Caco-2 cell culture model. J Nutr 1998; 128: 1555-1561
  • 26 Kraft M. Bindungsverhalten von Arsen, Cadmium, Chrom, Quecksilber, Nickel und Blei an schwerverdauliche Lebensmittel und Lebensmittelkomponenten in künstlichem Magen-Darm-Saft [doctoral thesis]. Bochum: Ruhr-Universität; 1998
  • 27 Maiwulanjiang M, Bi CW, Lee PS, Xin G, Miernisha A, Lau KM, Xiong A, Li N, Dong TT, Aisa HA, Tsim KW. The volatile oil of Nardostachyos Radix et Rhizoma induces endothelial nitric oxide synthase activity in HUVEC cells. PLoS One 2015; 10: e0116761