Constituents from the Leaves of Nelumbo nucifera Stimulate Lipolysis in the White Adipose Tissue of Mice

 

 Buy Article Permissions and Reprints

Abstract

Nelumbo nucifera Gaertn. (Nymphaceae) has been used for various medicinal purposes as in Chinese herbal medicine. In particular, the leaves are known for diuretic and astringent properties, and are used to treat obesity. During our search for a plant-derived anti-obesity agent from natural products, we have found that a 50 % ethanol (EtOH) extract prepared from the leaves of N. nucifera (NN) stimulated lipolysis in the white adipose tissue (WAT) of mice and that the β-adrenergic receptor (β-AR) pathway was involved in this effect. In subsequent experiments, dietary supplementation of NN resulted in a significant suppression of body weight gain in A/J mice fed a high-fat diet. Bioassay-guided fractionation and repeated chromatography of NN has led to the isolation and identification of quercetin 3-O-α-arabinopyranosyl-(1→2)-β-galactopyranoside (1), rutin (2), (+)-catechin (3), hyperoside (4), isoquercitrin (5), quercetin (6) and astragalin (7). Of these, compounds 1, 3, 4, 5 and 7 exhibited lipolytic activity, especially in visceral adipose tissue. Our results indicate that the effects of NN in preventing diet-induced obesity appear to be due to various flavonoids and that the activation of β-AR pathway was involved, at least in part.

References

• 1 Spiegelman B M, Flier J S. Obesity and the regulation of energy balance.  Cell. 2001;  104 531-43.
  CrossrefPubMedGoogle Scholar
• 2 Kao Y H, Chang H H, Lee M J, Chen C L. Tea, obesity, and diabetes.  Mol Nutr Food Res. 2006;  50 188-210.
  CrossrefPubMedGoogle Scholar
• 3 Vaughan M, Berger J E, Steinberg D. Hormone-sensitive lipase and monoglyceride lipase activities in adipose tissue.  J Biol Chem. 1964;  239 401-9.
  PubMedGoogle Scholar
• 4 Bachman E S, Dhillon H, Zhang C Y, Cinti S, Bianco A C, Kobilka B K. et al . βAR signaling required for diet-induced thermogenesis and obesity resistance.  Science. 2002;  297 843-5.
  CrossrefPubMedGoogle Scholar
• 5 Carmen G Y, Victor S M. Signalling mechanisms regulating lipolysis.  Cell Signal. 2006;  18 401-8.
  CrossrefPubMedGoogle Scholar
• 6 Ramis J M, Salinas R, Garcia-Sanz J M, Moreiro J, Proenza A M, Llado I. Depot- and gender-related differences in the lipolytic pathway of adipose tissue from severely obese patients.  Cell Physiol Biochem. 2006;  17 173-80.
  CrossrefPubMedGoogle Scholar
• 7 Tang W, Eisenbrand G. Chinese drugs of Plant Origin.  Berlin:. Springer-Verlag;  1992 697-701.
  PubMedGoogle Scholar
• 8 Ono Y, Hattori E, Fukaya Y, Imai S, Ohizumi Y. Anti-obesity effect of Nelumbo nucifera leaves extract in mice and rats. J.  Ethnopharmacol. 2006;  106 238-44.
  PubMedGoogle Scholar
• 9 Collins S, Daniel K W, Petro A E, Surwit R S. Strain-specific response to β3-adrenergic receptor agonist treatment of diet-induced obesity in mice.  Endocrinology. 1997;  138 405-13.
  CrossrefPubMedGoogle Scholar
• 10 Ikemoto S, Takahashi M, Tsunoda N, Maruyama K, Itakura H, Ezaki O. High-fat diet-induced hyperglycemia and obesity in mice: differential effects of dietary oils.  Metabolism. 1996;  45 1539-46.
  CrossrefPubMedGoogle Scholar
• 11 Rodbell M. Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis.  J Biol Chem. 1964;  239 375-80.
  PubMedGoogle Scholar
• 12 Li R, Keymeulen B, Gerlo E. Determination of glycerol in plasma by an automated enzymatic spectrophotometric procedure.  Clin Chem Lab Med. 2001;  39 20-4.
  CrossrefPubMedGoogle Scholar
• 13 Braca A, Prieto J M, De Tommasi N, Tome F, Morelli I. Furostanol saponins and quercetin glycosides from the leaves of Helleborus viridis L.  Phytochemistry. 2004;  65 2921-8.
  CrossrefPubMedGoogle Scholar
• 14 Sawabe A, Nesumi C, Morita M, Matsumoto S, Matsubara Y, Komemushi S. Glycosides in African dietary leaves , Hibiscus sabdariffa .  J Oleo Sci. 2005;  54 185-91.
  PubMedGoogle Scholar
• 15 Pouchert C J, Behnke J. The Aldrich library of ¹³C and ¹H FT NMR spectra. First edition, Vol. 2 Milwaukee; Aldrich Chemical Co 1993: 414.
  Google Scholar
• 16 Vvedenskaya I O, Rosen R T, Guido J E, Russell D J, Mills K A, Vorsa N i. Characterization of flavonols in cranberry (Vaccinium macrocarpon) powder.  J Agric Food Chem. 2004;  52 188-95.
  CrossrefPubMedGoogle Scholar
• 17 Pouchert C J, Behnke J. The Aldrich Library of ¹³C and ¹H FT NMR spectra. First edition, Vol. 2 Milwaukee; Aldrich Chemical Co 1993: 920.
  Google Scholar
• 18 Ardevol A, Blade C, Salvado M J, Arola L. Changes in lipolysis and hormone-sensitive lipase expression caused by procyanidins in 3T3-L1 adipocytes.  Int J Obes Relat Metab Disord. 2000;  24 319-24.
  CrossrefPubMedGoogle Scholar
• 19 Kuppusamy U R, Das N P. Effects of flavonoids on cyclic AMP phosphodiesterase and lipid mobilization in rat adipocytes.  Biochem Pharmacol. 1992;  44 1307-15.
  CrossrefPubMedGoogle Scholar
• 20 Pinent M, Blade M C, Salvado M J, Arola L, Ardevol A. Intracellular mediators of procyanidin-induced lipolysis in 3T3-L1 adipocytes.  J Agric Food Chem. 2005;  53 262-6.
  CrossrefPubMedGoogle Scholar
• 21 Arner P. Differences in lipolysis between human subcutaneous and omental adipose tissues.  Ann Med. 1995;  27 435-8.
  CrossrefPubMedGoogle Scholar
• 22 Boucher J, Castan-Laurell I, Le Lay S, Grujic D, Sibrac D, Valet P. et al . Human α2A-adrenergic receptor gene expressed in transgenic mouse adipose tissue under the control of its regulatory elements.  J Mol Endocrinol. 2002;  29 251-64.
  CrossrefPubMedGoogle Scholar

Dr. Hiroaki Yajima

Central Laboratories for Frontier Technology

1-13-5 Fukuura Kanazawa-ku

Yokohama-shi

Kanagawa 236-0004

Japan

Phone: +81-45-330-9004

Fax: +81-45-788-4047

Email: hyajima@kirin.co.jp

• Supplementary Material