Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Piceatannol-3'-O-${\beta}$-D-glucopyranoside as an active component of rhubarb activates endothelial nitric oxide synthase through inhibition of arginase activity

  • Woo, Ainieng (Department of Biology College of Natural Sciences Kangwon National University) ;
  • Min, Byung-Sun (College of Pharmacy Catholic University) ;
  • Ryoo, Sung-Woo (Department of Biology College of Natural Sciences Kangwon National University)
  • Accepted : 2010.06.10
  • Published : 2010.07.31
⟨ Previous Next ⟩

Abstract

Arginase competitively inhibits nitric oxide synthase (NOS) via use of the common substrate L-arginine. Arginase II has recently reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. Here, we demonstrate that piceatannol- 3'-O-${\beta}$-D-glucopyranoside (PG), a potent component of stilbenes, inhibits the activity of arginase I and II prepared from mouse liver and kidney lysates, respectively, in a dose-dependent manner. In human umbilical vein endothelial cells, incubation of PG markedly blocked arginase activity and increased NOx production, as measured by Griess assay. The PG effect was associated with increase of eNOS dimer ratio, although the protein levels of arginase II or eNOS were not changed. Furthermore, isolated mice aortic rings treated with PG showed inhibited arginase activity that resulted in increased nitric oxide (NO) production upto 78%, as measured using 4-amino-5-methylamino- 2',7'-difluorescein (DAF-FM) and a decreased superoxide anions up to 63%, as measured using dihydroethidine (DHE) in the intact endothelium. PG showed $IC_{50}$ value of 11.22 ${\mu}M$ and 11.06 ${\mu}M$ against arginase I and II, respectively. PG as an arginase inhibitor, therefore, represents a novel molecule for the therapy of cardiovascular diseases derived from endothelial dysfunction and may be used for the design of pharmaceutical compounds.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF), Korea Research Foundation

References

  1. Berkowitz DE, White R, Li D, Minhas KM, Cernetich A, Kim S, Burke S, Shoukas AA, Nyhan D, Champion HC, Hare JM. Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. Circulation 2003;108:2000-6 https://doi.org/10.1161/01.CIR.0000092948.04444.C7
  2. Bivalacqua TJ, Hellstrom WJ, Kadowitz PJ, Champion HC. Increased expression of arginase II in human diabetic corpus cavernosum: in diabetic-associated erectile dysfunction. Biochem Biophys Res Commun 2001;283:923-7 https://doi.org/10.1006/bbrc.2001.4874
  3. Bivalacqua TJ, Liu T, Musicki B, Champion HC, Burnett AL. Endothelial nitric oxide synthase keeps erection regulatory function balance in the penis. Eur Urol 2007;51:1732-40 https://doi.org/10.1016/j.eururo.2006.10.061
  4. Chicoine LG, Paffett ML, Young TL, Nelin LD. Arginase inhibition increases nitric oxide production in bovine pulmonary arterial endothelial cells. Am J Physiol Lung Cell Mol Physiol 2004;287:L60-8 https://doi.org/10.1152/ajplung.00194.2003
  5. Choi SZ, Lee SO, Jang KU, Chung SH, Park SH, Kang HC, Yang EY, Cho HJ, Lee KR. Antidiabetic stilbene and anthraquinone derivatives from Rheum undulatum. Arch Pharm Res 2005;28:1027-30 https://doi.org/10.1007/BF02977396
  6. Choi KH, Kim JE, Song NR, Son JE, Hwang MK, Byun S, Kim JH, Lee KW, Lee HJ. Phosphoinositide-3-kinase is a novel target of piceatannol for inhibiting PDGF-BB-induced proliferation and migration in human aortic smooth muscle cells. Cardiovasc Res 2009;85:836-44
  7. Christianson DW. Arginase: structure, mechanism, and physiological role in male and female sexual arousal. Acc Chem Res 2005;38:191-201 https://doi.org/10.1021/ar040183k
  8. Faffe DS, Flynt L, Mellema M, Whitehead TR, Bourgeois K, Panettieri RA Jr, Silverman ES, Shore SA. Oncostatin M causes VEGF release from human airway smooth muscle: synergy with IL-1beta. Am J Physiol Lung Cell Mol Physiol 2005;288:L1040-8 https://doi.org/10.1152/ajplung.00333.2004
  9. Holowatz LA, Thompson CS, Kenney WL. L-Arginine supplementation or arginase inhibition augments reflex cutaneous vasodilatation in aged human skin. J Physiol 2006;574:573-81 https://doi.org/10.1113/jphysiol.2006.108993
  10. Hsu LL, Champion HC, Campbell-Lee SA, Bivalacqua TJ, Manci EA, Diwan BA, Schimel DM, Cochard AE, Wang X, Schechter AN, Noguchi CT, Gladwin MT. Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability. Blood 2007;109: 3088-98
  11. Jang YJ, Kim JE, Kang NJ, Lee KW, Lee HJ. Piceatannol attenuates 4-hydroxynonenal-induced apoptosis of PC12 cells by blocking activation of c-Jun N-terminal kinase. Ann N Y Acad Sci 2009;1171:176-82 https://doi.org/10.1111/j.1749-6632.2009.04727.x
  12. Kim KO, Park SY, Han CW, Chung HK, Yoo DH, Han JS. Effect of sildenafil citrate on interleukin-1beta-induced nitric oxide synthesis and iNOS expression in SW982 cells. Exp Mol Med 2008;40:286-93 https://doi.org/10.3858/emm.2008.40.3.286
  13. Klasen S, Hammermann R, Fuhrmann M, Lindemann D, Beck KF, Pfeilschifter J, Racke K. Glucocorticoids inhibit lipopolysaccharide-induced up-regulation of arginase in rat alveolar macrophages. Br J Pharmacol 2001;132:1349-57 https://doi.org/10.1038/sj.bjp.0703951
  14. Li H, Meininger CJ, Hawker JR Jr, Haynes TE, Kepka-Lenhart D, Mistry SK, Morris SM, Jr., Wu G. Regulatory role of arginase I and II in nitric oxide, polyamine, and proline syntheses in endothelial cells. Am J Physiol Endocrinol Metab 2001;280:E75-82 https://doi.org/10.1152/ajpendo.2001.280.1.E75
  15. Li H, Meininger CJ, Kelly KA, Hawker JR Jr, Morris SM Jr, Wu G. Activities of arginase I and II are limiting for endothelial cell proliferation. Am J Physiol Regul Integr Comp Physiol 2002;282:R64-9 https://doi.org/10.1152/ajpregu.2002.282.1.R64
  16. Louis CA, Reichner JS, Henry WL Jr, Mastrofrancesco B, Gotoh T, Mori M, Albina JE. Distinct arginase isoforms expressed in primary and transformed macrophages: regulation by oxygen tension. Am J Physiol 1998;274:R775-82
  17. Matsuda H, Morikawa T, Toguchida I, Park JY, Harima S, Yoshikawa M. Antioxidant constituents from rhubarb: structural requirements of stilbenes for the activity and structures of two new anthraquinone glucosides. Bioorg Med Chem 2001;9:41-50 https://doi.org/10.1016/S0968-0896(00)00215-7
  18. Matsuda H, Tewtrakul S, Morikawa T, Yoshikawa M. Anti-allergic activity of stilbenes from Korean rhubarb (Rheum undulatum L.): structure requirements for inhibition of antigen-induced degranulation and their effects on the release of TNF-alpha and IL-4 in RBL-2H3 cells. Bioorg Med Chem 2004;12:4871-6 https://doi.org/10.1016/j.bmc.2004.07.007
  19. Modolell M, Corraliza IM, Link F, Soler G, Eichmann K. Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow-derived macrophages by TH1 and TH2 cytokines. Eur J Immunol 1995;25:1101-4 https://doi.org/10.1002/eji.1830250436
  20. Moon MK, Kang DG, Lee JK, Kim JS, Lee HS. Vasodilatory and anti-inflammatory effects of the aqueous extract of rhubarb via a NO-cGMP pathway. Life Sci 2006;78:1550-7 https://doi.org/10.1016/j.lfs.2005.07.028
  21. Morris SM Jr, Kepka-Lenhart D, Chen LC. Differential regulation of arginases and inducible nitric oxide synthase in murine macrophage cells. Am J Physiol 1998;275:E740-7
  22. Morris CR, Poljakovic M, Lavrisha L, Machado L, Kuypers FA, Morris SM, Jr. Decreased arginine bioavailability and increased serum arginase activity in asthma. Am J Respir Crit Care Med 2004;170:148-53 https://doi.org/10.1164/rccm.200309-1304OC
  23. Nelin LD, Wang X, Zhao Q, Chicoine LG, Young TL, Hatch DM, English BK, Liu Y. MKP-1 switches arginine metabolism from nitric oxide synthase to arginase following endotoxin challenge. Am J Physiol Cell Physiol 2007;293:C632-40 https://doi.org/10.1152/ajpcell.00137.2006
  24. Ngoc TM, Minh PT, Hung TM, Thuong PT, Lee I, Min BS, Bae K. Lipoxygenase inhibitory constituents from rhubarb. Arch Pharm Res 2008;31:598-605 https://doi.org/10.1007/s12272-001-1199-0
  25. Peyton KJ, Ensenat D, Azam MA, Keswani AN, Kannan S, Liu XM, Wang H, Tulis DA, Durante W. Arginase promotes neointima formation in rat injured carotid arteries. Arterioscler Thromb Vasc Biol 2009;29:488-94 https://doi.org/10.1161/ATVBAHA.108.183392
  26. Que LG, Kantrow SP, Jenkinson CP, Piantadosi CA, Huang YC. Induction of arginase isoforms in the lung during hyperoxia. Am J Physiol 1998;275:L96-102
  27. Ryoo S, Lemmon CA, Soucy KG, Gupta G, White AR, Nyhan D, Shoukas A, Romer LH, Berkowitz DE. Oxidized low-density lipoprotein-dependent endothelial arginase II activation contributes to impaired nitric oxide signaling. Circ Res 2006;99:951-60 https://doi.org/10.1161/01.RES.0000247034.24662.b4
  28. Ryoo S, Gupta G, Benjo A, Lim HK, Camara A, Sikka G, Sohi J, Santhanam L, Soucy K, Tuday E, Baraban E, Ilies M, Gerstenblith G, Nyhan D, Shoukas A, Christianson DW, Alp NJ, Champion HC, Huso D, Berkowitz DE. Endothelial arginase II: a novel target for the treatment of atherosclerosis. Circ Res 2008;102:923-32 https://doi.org/10.1161/CIRCRESAHA.107.169573
  29. Simon A, Plies L, Habermeier A, Martine U, Reining M, Closs EI. Role of neutral amino acid transport and protein breakdown for substrate supply of nitric oxide synthase in human endothelial cells. Circ Res 2003;93:813-20 https://doi.org/10.1161/01.RES.0000097761.19223.0D
  30. Steppan J, Ryoo S, Schuleri KH, Gregg C, Hasan RK, White AR, Bugaj LJ, Khan M, Santhanam L, Nyhan D, Shoukas AA, Hare JM, Berkowitz DE. Arginase modulates myocardial contractility by a nitric oxide synthase 1-dependent mechanism. Proc Natl Acad Sci USA 2006;103:4759-64 https://doi.org/10.1073/pnas.0506589103
  31. Takimoto E, Champion HC, Li M, Ren S, Rodriguez ER, Tavazzi B, Lazzarino G, Paolocci N, Gabrielson KL, Wang Y, Kass DA. Oxidant stress from nitric oxide synthase-3 uncoupling stimulates cardiac pathologic remodeling from chronic pressure load. J Clin Invest 2005;115:1221-31 https://doi.org/10.1172/JCI21968
  32. Vo TP, Madlener S, Bago-Horvath Z, Herbacek I, Stark N, Gridling M, Probst P, Giessrigl B, Bauer S, Vonach C, Saiko P, Grusch M, Szekeres T, Fritzer-Szekeres M, Jager W, Krupitza G, Soleiman A. Pro- and anti-carcinogenic mechanisms of piceatannol are activated dose-dependently in MCF-7 breast cancer cells. Carcinogenesis. 2009 [Epub Ahead of Print]
  33. White AR, Ryoo S, Li D, Champion HC, Steppan J, Wang D, Nyhan D, Shoukas AA, Hare JM, Berkowitz DE. Knockdown of arginase I restores NO signaling in the vasculature of old rats. Hypertension 2006;47:245-51
  34. Xu X, Gao X, Potter BJ, Cao JM, Zhang C. Anti-LOX-1 rescues endothelial function in coronary arterioles in atherosclerotic ApoE knockout mice. Arterioscler Thromb Vasc Biol 2007;27:871-7 https://doi.org/10.1161/01.ATV.0000259358.31234.37
  35. Yoo MY, Oh KS, Lee JW, Seo HW, Yon GH, Kwon DY, Kim YS, Ryu SY, Lee BH. Vasorelaxant effect of stilbenes from rhizome extract of rhubarb (Rheum undulatum) on the contractility of rat aorta. Phytother Res 2007;21:186-9 https://doi.org/10.1002/ptr.2042
  36. Zhang C, Hein TW, Wang W, Chang CI, Kuo L. Constitutive expression of arginase in microvascular endothelial cells counteracts nitric oxide-mediated vasodilatory function. Faseb J 2001;15:1264-6 https://doi.org/10.1096/fj.00-0681fje

Cited by

  1. Arginase Inhibition by Ethylacetate Extract of Caesalpinia sappan Lignum Contributes to Activation of Endothelial Nitric Oxide Synthase vol.15, pp.3, 2010, https://doi.org/10.4196/kjpp.2011.15.3.123
  2. Tannins of Constant Structure in Medicinal and Food Plants—Hydrolyzable Tannins and Polyphenols Related to Tannins vol.16, pp.3, 2010, https://doi.org/10.3390/molecules16032191
  3. Antioxidant effects of resveratrol and other stilbene derivatives on oxidative stress and ?NO bioavailability: Potential benefits to cardiovascular diseases vol.94, pp.2, 2012, https://doi.org/10.1016/j.biochi.2011.11.001
  4. Syringaresinol causes vasorelaxation by elevating nitric oxide production through the phosphorylation and dimerization of endothelial nitric oxide synthase vol.44, pp.3, 2010, https://doi.org/10.3858/emm.2012.44.3.014
  5. Salvianolic Acid B Exerts Vasoprotective Effects through the Modulation of Heme Oxygenase-1 and Arginase Activities vol.341, pp.3, 2010, https://doi.org/10.1124/jpet.111.190736
  6. Arginase II Inhibitory Activity of Phenolic Compounds from Saururus chinensis vol.33, pp.9, 2012, https://doi.org/10.5012/bkcs.2012.33.9.3079
  7. Increased arginase II activity contributes to endothelial dysfunction through endothelial nitric oxide synthase uncoupling in aged mice vol.44, pp.10, 2010, https://doi.org/10.3858/emm.2012.44.10.068
  8. Arginase II inhibitory activity of flavonoid compounds from Scutellaria indica vol.36, pp.8, 2013, https://doi.org/10.1007/s12272-013-0125-3
  9. Development of Novel Arginase Inhibitors for Therapy of Endothelial Dysfunction vol.4, pp.None, 2013, https://doi.org/10.3389/fimmu.2013.00278
  10. Arginase inhibition by piceatannol-3′-O-β-D-glucopyranoside improves endothelial dysfunction via activation of endothelial nitric oxide synthase in ApoE-null mice fed a high-cholesterol diet vol.31, pp.4, 2013, https://doi.org/10.3892/ijmm.2013.1261
  11. Korean red ginseng inhibits arginase and contributes to endothelium-dependent vasorelaxation through endothelial nitric oxide synthase coupling vol.37, pp.1, 2010, https://doi.org/10.5142/jgr.2013.37.64
  12. Endothelial nitric oxide synthase activation through obacunone-dependent arginase inhibition restored impaired endothelial function in ApoE-null mice vol.60, pp.3, 2010, https://doi.org/10.1016/j.vph.2014.01.006
  13. Korean Red Ginseng Water Extract Restores Impaired Endothelial Function by Inhibiting Arginase Activity in Aged Mice vol.18, pp.2, 2010, https://doi.org/10.4196/kjpp.2014.18.2.95
  14. Resveratrol prevents hypoxia-induced arginase II expression and proliferation of human pulmonary artery smooth muscle cells via Akt-dependent signaling vol.307, pp.4, 2010, https://doi.org/10.1152/ajplung.00285.2013
  15. A Review of the Pharmacological Effects of Piceatannol on Cardiovascular Diseases vol.28, pp.11, 2014, https://doi.org/10.1002/ptr.5185
  16. Arginase as a Critical Prooxidant Mediator in the Binomial Endothelial Dysfunction-Atherosclerosis vol.2015, pp.None, 2010, https://doi.org/10.1155/2015/924860
  17. Pharmacokinetics and Pharmacodynamics of Promising Arginase Inhibitors vol.42, pp.3, 2010, https://doi.org/10.1007/s13318-016-0381-y
  18. Synthesis, Anti-inflammatory, and Arginase Inhibitory Activity of Piceatannol and Its Analogs : Synthesis and Activity of Piceatannol Derivatives vol.38, pp.3, 2017, https://doi.org/10.1002/bkcs.11089
  19. Cyperaceae Species Are Potential Sources of Natural Mammalian Arginase Inhibitors with Positive Effects on Vascular Function vol.80, pp.9, 2010, https://doi.org/10.1021/acs.jnatprod.7b00197
  20. Comparative Pharmacokinetics and Metabolic Profile of Rhein Following Oral Administration of Niuhuang Shang Qing Tablets, Rhubarb and Rhein in Rats vol.15, pp.1, 2010, https://doi.org/10.3923/ijp.2019.19.30
  21. PERSPECTIVES OF WOOD-GREENERY BIOTECHNOLOGY ENRICHMENT WITH L-ARGININE AND INHIBITORS OF ITS CATABOLISM vol.2019, pp.1, 2010, https://doi.org/10.14258/jcprm.2019014243
  22. Piceatannol-3-O-β-D-glucopyranoside (PG) exhibits in vitro anti-metastatic and anti-angiogenic activities in HT1080 malignant fibrosarcoma cells vol.57, pp.None, 2010, https://doi.org/10.1016/j.phymed.2018.12.017
  23. p32-Dependent p38 MAPK Activation by Arginase II Downregulation Contributes to Endothelial Nitric Oxide Synthase Activation in HUVECs vol.9, pp.2, 2010, https://doi.org/10.3390/cells9020392
  24. Synthesis, evaluation and molecular modelling of piceatannol analogues as arginase inhibitors vol.11, pp.5, 2020, https://doi.org/10.1039/d0md00011f
  25. Arginase as a Potential Biomarker of Disease Progression: A Molecular Imaging Perspective vol.21, pp.15, 2020, https://doi.org/10.3390/ijms21155291