Effect of Dietary Supplementation of Procyanidin on Growth Performance and Immune Response in Pigs

  • Park, J.C. ;
  • Lee, S.H. ;
  • Hong, J.K. ;
  • Cho, J.H. ;
  • Kim, I.H. ;
  • Park, S.K.
  • Received : 2013.05.24
  • Accepted : 2013.10.11
  • Published : 2014.01.01


This study was performed to determine the effect of dietary supplementation of procyanidin on growth performance, blood characteristics, and immune function in growing pigs. In experiment 1 (Exp. 1), thirty-two crossbred pigs with an initial BW of $19.2{\pm}0.3$ kg were allocated into 4 treatments for an 8-wk experiment: i) CON (basal diet), ii) MOS 0.1 (basal diet+0.1% mannanoligosaccharide), iii) Pro-1 (basal diet+0.01% procyanidin), and iv) Pro-2 (basal diet+0.02% procyanidin). Pigs fed Pro-1 and Pro-2 diets had greater (p<0.05) gain:feed ratio compared with those fed CON or MOS 0.1 diets. Serum creatinine concentration was less (p<0.05) in Pro-2 treatment than those in CON, MOS 0.1 and Pro-1 treatments. In Exp. 2, twelve pigs (BW $13.4{\pm}1.3$ kg) received basal diet with i) 0 (CON), ii) 0.02% (Pro-0.02%), and iii) 0.04% procyanidin (Pro-0.04%) for 4 wk. Concentration of platelets was lower (p<0.05) in the Pro-0.04% group compared to CON at 24 h after lipopolysaccharide (LPS) challenge. In addition, secretion of cytokines from cultured peripheral blood mononuclear cells (PBMC) in the presence or absence of procyanidin was examined. The levels of interleukin (IL)-$1{\beta}$, IL-6 and tumor necrosis factor (TNF)-${\alpha}$ were lower (p<0.05) in Pro (LPS-stimulated PBMCs+procyanidin) than those in CON (LPS-stimulated PBMCs+PBS) at 4 h after LPS challenge. These data suggest that dietary addition of procyanidin improves feed efficiency and anti-inflammatory cytokines of pigs.


Growth Performance;Immune Response;Lipopolysaccharide;Pigs;Procyanidin


  1. Freedman, J. E., C. III. Parker, L. Li, J. A. Perlman, B. Frei, V. Ivanov, L. R. Deak, M. D. Iafrati, and J. D. Folts. 2001. Select flavonoids and whole juice from purple grapes inhibit platlet function and enhance nitric oxide release. Circulation 103:2792-2798.
  2. Chen, S. T., S. J. Peng, and J. R. Chen. 2003. Effects of dietary protein on renal function and lipid metabolism in five-sixths nephrectomized rats. Br. J. Nutr. 89:491-497.
  3. Cho, J. H., Y. J. Chen, B. J. Min, H. J. Kim, O. S. Kwon, K. S. Shon, I. H. Kim, S. J. Kim, and A. Asamer. 2006. Effects of essential oils supplementation on growth performance, IgG concentration and fecal noxious gas concentration of weaned pigs. Asian-Aust. J. Anim. Sci. 19:80-85.
  4. Cos, P., T. de Bruyne, N. Hermans, S. Apers, D. V. Berghe, and A. J. Vlietinck. 2004. Proanthocyanidins in health care: Current and new trend. Curr. Med. Chem. 11:1345-1359.
  5. Daughenbaugh, K. F., J. Holderness, J. C. Graff, J. F. Hedges, B. Freedman, J. W. Graff, and M. A. Jutila. 2011. Contribution of transcript stability to a conserved procyanidin-induced cytokine response in ${\gamma} {\delta}T$ cells. Genes Immun. 12:378-389.
  6. Demrow, H. S., P. R. Slane, and J. D. Folts. 1995. Administration of wine and grape juice inhibits in vivo platelet activity and thrombosis in stenosed canine coronary arteries. Circulation 91:1182-1188.
  7. Duncan, D. B. 1955. Multiple range and multiple F tests. Biometrics 11:1-42.
  8. Erlejman, A. G., G. Jaggers, C. G. Fraga, and P. I. Oteiza. 2008. $TNF\alpha$-induced NF-$_{k}B$ activation and cell oxidant production are modulated by hezameric procyanidins in Caco-2 cells. Arch. Biochem. Biophys. 476:186-195.
  9. Faria, A., C. Calhau, V. de Freitas, and N. Mateus. 2006. Procyanidins as antioxidants and tumor cell growth modulators. J. Agric. Food Chem. 54:2392-2397.
  10. Karen, J. K., K. C. Andriana, S. Indu, A. F. Maureen, M. Helen, J. P. Marilyn, H. T. Alan, J. M. Neil, and J. S. Andrew. 2003. Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function. Am. J. Clin. Nutr. 77:1466-1473.
  11. Karin, M. and F. R. Greten. 2005. NFkB: Linking inflammation and immunity to cancer development and progression. Nat. Rev. Immunol. 5:749-759.
  12. Khan, M. A. 1999. Chemical composition and medicinal properties of Nigella sativa Linn. Inflammopharmacology 7:15-35.
  13. Kim, B. G., M. D. Lindemann, and G. L. Cromwell. 2010. The effects of dietary chromium (III) picolinate on growth performance, vital signs, and blood measurements of pigs during immune stress. Biol. Trace Elem. Res. 135:200-210.
  14. Bentivegna, S. S. and K. M. Whitney. 2002. Subchronic 3-month oral toxicity study of grape seed and grape skin extracts. Food Chem. Toxicol. 40:1731-1743.
  15. Bae, K. H., T. G. Ko, J. H. Kim, W. T. Cho, Y. K. Han, and I. K. Han. 1999. Use of metabolically active substances to substitute for antibiotics in finishing pigs. Korean J. Anim. Sci. 41:23-30.
  16. Balu, M., P. Sageetja, D. Haripriya, and C. Panneerselvam. 2005. Rejuvenation of antioxidant system in central nervous system of aged rats by grape seed extract. Neurosci. Lett. 383:295-300.
  17. Brenes, A., A. Viveros, I. Goni, C. Centeno, F. Saura-Calixto, and I. Arija. 2010. Effect of grape seed extract on growth performance, protein and polyphenol digestibilities, and antioxidant activity in chickens. Span. J. Agric. Res. 8:326-333.
  18. Chang, W. C. and F. L. Hsu. 1989. Inhibition of platelet aggregation and arachidonate metabolism in platelets by procyanidins. Prostaglandins Leukot. Essent. Fatty Acids 38:181-1888.
  19. Holderness, J., L. Jackiw, E. Kimmel, H. Kerns, M. Radke, J. F. Hedges, C. Petrie, P. McCurley, P. M. Glee, A. Palecanda, and M. A. Jutila. 2007. Select plant tannins induce IL-2R up-regulation and augment cell division in ${\gamma}{\delta}T$ cells. J. Immunol. 179:6468-6478.
  20. Hong, J. W., I. H. Kim, O. S. Kwon, B. J. Min, W. B. Lee, and K. S. Shon. 2004. Influences of plant extract supplementation on performance and blood characteristics in weaned pigs. Asian-Aust. J. Anim. Sci. 17:374-378.
  21. Huang, Y., J. S. Yoo, H. J. Kim, Y. Wang, Y. J. Chen, J. H. Cho, and I. H. Kim. 2010. Effects of dietary supplementation with blended essential oils on growth performance, nutrient digestibility, blood profiles and fecal characteristics in weanling pigs. Asian-Aust. J. Anim. Sci. 23:607-613.
  22. Hwang, D. S., S. Y. Shin, Y. G. Lee, J. Y. Hyun, Y. J. Yong, J. C. Park, Y. H. Lee, and Y. H. Lim. 2011. A compound isolated from Schisandra chinensis induces apoptosis. Bioorg. Med. Chem. Lett. 21:6054-6057.
  23. Hwang, I. W., H. R. Lee, S. K. Kim, H. Z. Zheng, J. U. Choi, S. H. Lee, S. H. Lee, and S. K. Chung. 2008. Proanthocyanidin content and antioxidant characteristics of grape seeds. Korean J. Food Preserv. 15:859-863.
  24. Jeong, S. M., S. Y. Kim, J. U. Ha, and S. C. Lee. 2005. Effect of far-infrared irradiation on the antioxidant activity of extracts from grape seed. J. Korean Soc. Food Sci. Nutr. 34:1619-1624.
  25. Johnson, R. W. 1997. Inhibition of growth by pro-inflammatory cytokines: An integrated view. J. Anim. Sci. 75:1244-1255.
  26. Kalantari, H., I. Rashidi, S. Bazgir, and A. Dibaei. 2007. Protective effects of hydroalcoholic extract of red grape seed (VITIS VENIFERA) in nephrotoxicity induced by amikacin in mice. Jund. J. Nat. Parm. Products 2:87-93.
  27. Marklund, S. and G. Marklund. 1974. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem. 47:469-474.
  28. Martinez-Micaelo, N., N. Gonzalez-Abuin, X. Terra, C. Richart, A. Ardevol, M. Pinent, and M. Blay. 2012. Omega-3 docosahexaenoic acid and procyanidins inhibit cyclo-oxygenase activity and attenuate NF-kB activation through a p105/p50 regulatory mechanism in macrophage inflammation. Biochem. J. 441:653-663.
  29. Mathieson, P. W. 2003. Immune dysregulation in minimal change nephropathy. Nephrol. Dial. Transplant. 6:26-29.
  30. Matteri, R. L., J. J. Klir, B. N. Fink, and R. W. Johnson. 1998. Neuroendocrine-immune interactions in the neonate. Domest. Anim. Endocrinol. 15:397-407.
  31. McCord, J. M. 2000. The evolution of free radicals and oxidative stress. Am. J. Med. 108:652-659.
  32. Meng, Q. W., L. Yan, X. Ao, H. D. Jang, J. H. Cho, and I. H. Kim. 2010. Effects of chito-oligosaccharide supplementation on egg production, nutrient digestibility, egg quality and blood profiles in laying hens. Asian-Aust. J. Anim. Sci. 23:1476-1481.
  33. Mohanasundari, M., M. Sabesan, and S. Sethupathy. 2005. Renoprotective effect of grape seeds extract in ethylene glycol induced nephrotoxic mice. Indian J. Exp. Biol. 43:356-359.
  34. National Institute of Animal Science (NIAS). 2007. Korean feeding standard for Swine, Korea.
  35. Garcia, J., N. Nicodemus, R. Carabano and J. C. de Blass. 2002. Effect of inclusion of defated grape seed meal in the diet on digestion and performance of growing rabbits. J. Anim. Sci. 80:162-170.
  36. Han, J. Y., J. H. Sung, D. J. Kim, H. S. Jeong, and J. S. Lee. 2008. Inhibitory effect of methanol extract and its fractions from grape seeds on mushroom tyrosinase. J. Korean Soc. Food Sci. Nutr. 37:1679-1683.
  37. Sakaguchi, Y., H. Shirahase, K. Kunishiro, A. Ichikawa, M. Kanda, and Y. Uehara. 2006. Effect of combination of nitric oxide synthase and cyclooxygenase inhibitors on carrageenan-induced pleurisy in rats. Life Sci. 79:442-447.
  38. Lee, E. 2007. Anti-inflammatory effect of Scutellariae Radix. Korean J. Pant. Res. 20:548-552.
  39. Li, W. G., X. Y. Zhang, Y. J. Wu, and X. Tian. 2001. Anti-inflammatory effect and mechanism of proanthocyanidins from grape seeds. Acta. Pharmacol. Sin. 22:1117-1120.
  40. Lluis, L., M. Munoz, M. R. Nogues, V. S. Martos, M. Romeu, M. Giralt, J. Valls, and R. Sola. 2011. Toxicology evaluation of a procyanidin-rich extract from grape skins and seeds. Food Chem. Toxicol. 49:1450-1454.
  41. Lohakare, J. D., M. H. Ryu, T. W. Hahn, J. K. Lee, and B. J. Chae. 2005. Effects of supplemental ascorbic acid on the performance and immunity of commercial broilers. J. Appl. Poult. Res. 14:10-19.
  42. Mackenzie, G. G., F. Carrasquedo, J. M. Delfino, C. L. Keen, C. G. Fraga, and P. I. Oteiza. 2004. Epicatechin, catechin, and dimeric procyanidins inhibit PMA-induced NF-$_{\kappa}B$ activation at multiple steps in Jurkat T cells. FASEB J. 18:167-169.
  43. Mao, T. K., J. J. Powell, J. van de Water, C. L. Keen, H. H. Schmitz, and M. E. Gershwin. 1999. The influence of cococa procyanidins on the transcription of interleukin-2 in peripheral blood mononuclear cells. Int. J. Immunother. 15:23-29.
  44. Mao, X. F., X. S. Piao, C. H. Lai, D. F. Li, J. J. Xing, and B. L. Shi. 2005. Effect of $\beta$-glucan obtained from the chinese herb Astragalus membranaceus and lipopolysaccharide challenge on performance, immunological, adrenal, and somatotropic responses of weanling pigs. J. Anim. Sci. 83:2775-2782.
  45. Prieur, C., J. Rigaud, V. Cheyner, and M. Moutounet. 1994. Oligomeric and polymeric procyanidin from grape seed. Phytochemistry 36:781-784.
  46. Pu, Q., E. Wiel, D. Corseaux, R. Bordet, M. A. Azrin, M. D. Ezekowitz, N. Lund, B. Jude, and B. Vallet. 2001. Beneficial effect of glycoprotein IIb/IIIa inhibitor (AZ-1) on endothelium in Escherichia coli endotoxin-induced shock. Crit. Care Med. 29:1181-1188.
  47. Rein, D., T. G. Paglieroni, D. A. Pearson, T. Wun, H. H. Schmitz, R. Gosselin, and C. L. Keen. 2000. Cocoa and wine polyphenols modulate platelet activation and function. J. Nutr. 130:2120S-2126S.
  48. Ruf, J. C., J. L. Berger, and S. Renaud. 1995. Platelet rebound effect of alcohol withdrawal and wine drinking in rats. Relation to tannins and lipid peroxidation. Arterioscler. Thromb. Vasc. Biol. 15:140-144.
  49. Rumbaut, R. E., R. V. Bellera, J. K. Randhawa, C. N. Shrimpton, S. K. Dasgupta, J. F. Dong, and A. R. Burns. 2006. Endotoxin enhaces microvascular thrombosis in mouse cremaster venules via a TKR4-dependent, neutrophil-independent mechanism. Am. J. Physiol. Heart Circ. Physiol. 290:H1671-1679.
  50. Ricardo da Silva, J. M., J. P. Rosec, M. Bourzeix, and N. Heredia. 1990. Separation and quantitative determination of grape and wine procyanidins by high performance reversed phase liquid chromatography. J. Sci. Food Agric. 53:85-92.
  51. Sanbongi, C., N. Sizuki, and T. Sakane. 1997. Polyphenols in chocolate, which have antioxidant activity, modulate immune function in humans in vitro. Cell. Immunol. 177:129-136.
  52. SAS Institute. 2008. SAS user's guide, Statistical Analysis System Inst. Inc Cary NC.
  53. Safa, J., H. Argani, B. Bastani, N. Nezami, B. Rahimi Ardebili, A. Ghorbanihaghjo, H. Kalagheichi, A. Amirfirouzi, M. Mesgari, and J. Soleimany Rad. 2010. Protective effect of grape seed extract on gentamicin-induced acute kidney injury. Iran. J. Kidney Dis. 4:285-291.
  54. Wooden, G. R., C. S. Crane, and C. G. Beisel. 1984. An investigation of the effect of hesperidin complex and lemon bioflavonoid complex on growth and development of thoroughbred horses. J. Anim. Sci. 59:1529-1535.
  55. Wright, K. J., R. Balaji, C. M. Hill, S. S. Dritz, E. L. Knoppel, and J. E. Minton. 2000. Integrated adrenal, somatotropic, and immune responses of growing pigs to treatment with lipopolysaccharide. J. Anim. Sci. 78:1892-1899.
  56. Yahara, N., I. Tofani, K. Maki, K. Kojima, Y. Kijima, and M. Kimura. 2005. Mechanical assessment of effects of grape seed proanthocyanidins extract on tibial bone diaphysis in rats. J. Musculoskelet Neuronal Interact 5:162-169.
  57. Yamakoshi, J., M. Saito, S. Kataoka, and M. Kikuchi. 2002. Safety evaluation of proanthocyanidin-rich extract from grape seeds. Food Chem. Toxicol. 40:599-607.
  58. Yanarates, O., A. Guven, A. Sizlan, B. Uysal, O. Akgul, A. Atim, A. Ozcan, A. Korkmaz, and E. Kurt. 2008. Ameliorative effects of proanthocyanidin on renal ischemia/reperfusion injury. Ren. Fail. 30:931-938.
  59. Nordberg, J. and E. S. Arner. 2001. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic. Biol. Med. 31:1287-1312.
  60. Oguntibeju, O. O., A. N. Fashola, and C. L. Cole-Showers. 2012. Effects of procyanidin on antioxidant enzyme status in kidney and heart homogenates of Wistar rats. J. Food Agric. Environ. 10:34-37.
  61. Pasinetti, G. M., H. Ksiezak-Reding, I. Santa-Maria, J. Wang, and L. Ho. 2010. Development of grape seed polyphenolic extract with anti-oligomeric activity as a novel treatment in progressive supranuclear palsy and other tauopathies. J. Neurochem. 114:1557-1568.
  62. Pignatelli, P., F. M. Pulcinelli, A. Celestini, L. Lenti, A. Ghiselli, P. P. Gazzaniga, and F. Violi. 2000. The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxidase. Am. J. Clin. Nutr. 72:1150-1155.
  63. Zhang, W. Y., H. Q. Liu, K. Q. Xie, L. L. Yin, Y. Li, C. L. Kwik-Uribe, and X. Z. Zhu. 2006. Procyanidin dimer B2 [epicatechin-($4\beta$-8)-epicatechin] suppresses the expression of cyclooxygenase-2 in endotoxin-treated monocytic cells. Biochem. Biophys. Res. Commun. 345:508-515.
  64. Zhao, L., Y. Ohtaki, K. Yamaguchi, M. Matsushita, T. Fujita, T. Yokochi, H. Takada, and Y. Endo. 2002. LPS-induced platelet response and rapid shock in mice: contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system. Blood 100:3233-3239.
  65. Yang, X., Y. Guo, X. He, J. Yuan, Y. Yang, and Z. Wang. 2008. Growth performance and immune responses in chickens after challenge with lipopolysaccharide and modulation by dietary different oils. Animal 2:216-223.
  66. Zhang, G., J. Han, E. J. Welch, R. D. Ye, T. A. Voyno-Yasenetskaya, A. B. Malik, X. Du, and Z. Li. 2009. Lipopolysaccharide stimulates platelet secretion and potentiates platelet aggregation via TLR4/MyD88 and the cGMP-dependent protein kinase pathway. J. Immunol. 182:7997-8004.
  67. Sangeetha, P., M. Balu, D. Haripriya, and C. Panneerselvam. 2005. Age associated change in erythrocyte membrane surface charge: Modulatory role of grape seed proanthocyanidin. Exp. Gerontol. 40:820-828.
  68. Selmi, C., T. K. Mao, C. L. Keen, H. H. Schmitz, and M. Eric Gershwin. 2006. The anti-inflammatory properties of cocoa flavanols. J. Cardiovasc. Pharmacol. 47:S163-S171.
  69. Shi, J., J. Yu, J. E. Pohorly, and Y. Kakuda. 2003. Polyphenolics in grape seeds-biochemistry and functionality. J. Med. Food 6:291-299.
  70. Slayback, L. D. and R. W. Ronald. 2006. Bioflavonoids and cardiovascular health: tea, red wine, cocoa and $pycnogenol^{(R)}$. J. Am. Nutrac. Assoc. 9:16-21.
  71. Spurlock, M. E. 1997. Regulation of metabolism and growth during immune challenge: an overview of cytokine function. J. Anim. Sci. 75:1773-1783.
  72. Taylor, F. B., B. S. Coller, A. C. Chang, G. Peer, R. Jordan, W. Engellener, and C. T. Esmon. 1997. 7E3 F(ab')2, a monoclonal antibody to the platelet GPIIb/IIIa receptor, protects against microangiopathic hemolytic anemia and microvascular thrombotic renal failure in baboons treated with C4b binding protein and a sublethal infusion of Escherichia coli. Blood 89: 4078-4084.
  73. Terra, X., G. Montagut, M. Bustos, N. Llopiz, A. Ardevol, C. Blade, J. Fernandez-Larrea, G. Pujadas, J. Salvado, L. Arola, and M. Blay. 2009. Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet. J. Nutr. Biochem. 20:210-218.
  74. Tizard, I. R. 2000. Veterinary immunology: An introduction. W.B. Sauders Company. Philadelphia, PA.
  75. Tracey, K. J., A. Cerami. 1994. Tumor Necrosis Factor: A pleiotropic cytokine and therapeutic target. Annu. Rev. Med. 45:491-503.
  76. Windisch, W. M., K. Schedle, C. Plitzner, and A. Kroismayr. 2008. Use of phytogenic products as feed additives for swine and poultry. J. Anim. Sci. 86:E140-148.

Cited by

  1. Induction of cellular and molecular immunomodulatory pathways by vitamin A and flavonoids vol.15, pp.10, 2015,
  2. Characterization of the Fecal Microbial Communities of Duroc Pigs Using 16S rRNA Gene Pyrosequencing vol.28, pp.4, 2015,
  3. Microbial composition in different gut locations of weaning piglets receiving antibiotics vol.30, pp.1, 2016,
  4. sp. in swine: insights from gut microbiota vol.122, pp.3, 2017,
  5. Protective effect of proanthocyanidin on mice Sertoli cell apoptosis induced by zearalenone via the Nrf2/ARE signalling pathway vol.24, pp.34, 2017,


Grant : cooperative research program for Agriculture Science & Technology Development

Supported by : Rural Development Administration