Advertisement

Inflammation

pp 1–16 | Cite as

Improvement of Resveratrol Effects When Combined with Rice Oil in Rat Models of Inflammation

  • Rodrigo B. M. SilvaEmail author
  • Izaque S. Maciel
  • Alice Ribeiro
  • Gabriel Rübensam
  • Andressa Bernardi
  • Fernanda B. Morrone
  • Andre A. Souto
  • Maria M. Campos
Original Article
  • 72 Downloads

Abstract

This study investigated the effects of systemic treatment with a new formulation of resveratrol (RSV) vehicled in rice oil (RSVO) in experimental rat models of inflammation. Male Wistar rats were evaluated in the following in vivo models: carrageenan-induced acute edema, complete Freund’s adjuvant (CFA)-evoked sub-chronic edema, and CFA-induced polyarthritis. The animals were treated orally with RSVO (10–15 mg/kg) or RSV (100–200 mg/kg), depending on the experimental protocol. RSV was more effective than RSVO in carrageenan-elicited acute edema when dosed in either prophylactic or therapeutic schemes of administration. However, the repeated RSVO administration, at 10-fold lower doses, exhibited superior anti-inflammatory actions in either the sub-chronic edema or the chronic polyarthritis model elicited by CFA, when compared with RSV. The novel formulation RSVO displayed a lower plasma biotransformation when compared with the RSV-treated group—46% versus 88% of metabolites, respectively. RSVO also prevented polyarthritis-related cartilage destruction, an effect that might rely on the inhibition of the pro-inflammatory cytokine interleukin-6 (IL-6), associated with an increase of the anti-inflammatory cytokine interleukin-10 (IL-10). Noteworthy, the long-term administration of RSVO did not elicit any gastrointestinal harm. Our study revealed that RSVO was notably effective in the long-term inflammatory and degenerative responses triggered by CFA. This innovative formulation might well represent a promising alternative for treating chronic inflammatory diseases, such as arthritis.

KEY WORDS

acute and chronic inflammation polyarthritis complete Freund’s adjuvant resveratrol resveratrol vehicled in rice oil 

Notes

Acknowledgments

We would like to thank Mr. Juliano Soares and Mrs. Janaína Pasetti Nunes for their excellent technical assistance. Our work was supported by Financiadora de Estudos e Projetos (FINEP, Brazil) research grant “Implantação, Modernização e Qualificação de Estrutura de Pesquisa da PUCRS” (PUCRSINFRA) # 01.11.0014-00. Rodrigo B. M. Silva is postdoctoral fellowship receiving grants from National Institute of Science and Technology in Tuberculosis (INCT-TB). Maria M. Campos is a researcher career awardee of Conselho Nacional de Ciência e Tecnologia (CNPq; 304042/2018-8). Fernanda B. Morrone is a researcher career awardee of Conselho Nacional de Ciência e Tecnologia (CNPq; 310317/2018-5).

Compliance with Ethical Standards

The Institutional Animal Ethics Committee approved all the experimental protocols used in the present study.

Conflict of Interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Schett, Georg, and Markus F. Neurath. 2018. Resolution of chronic inflammatory disease: universal and tissue-specific concepts. Nature Communications 9: 1–8.  https://doi.org/10.1038/s41467-018-05800-6.CrossRefGoogle Scholar
  2. 2.
    Cicero, F.G. Arrigo, Federica Fogacci, and Alessandro Colletti. 2017. Potential role of bioactive peptides in prevention and treatment of chronic diseases: a narrative review. British Journal of Pharmacology.  https://doi.org/10.1111/bph.13608.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Nawaz, Waqas, Zhongqin Zhou, Sa Deng, Xiaodong Ma, Xiaochi Ma, Chuangang Li, and Xiaohong Shu. 2017. Therapeutic versatility of resveratrol derivatives. Nutrients.  https://doi.org/10.3390/nu9111188.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Catalgol, Betul, Saime Batirel, Yavuz Taga, and Nesrin Kartal Ozer. 2012. Resveratrol: French paradox revisited. Frontiers in Pharmacology.  https://doi.org/10.3389/fphar.2012.00141.
  5. 5.
    Oliviero, Francesca, Anna Scanu, Yessica Zamudio-Cuevas, Leonardo Punzi, and Paolo Spinella. 2018. Anti-inflammatory effects of polyphenols in arthritis. Journal of the Science of Food and Agriculture.  https://doi.org/10.1002/jsfa.8664.PubMedCrossRefGoogle Scholar
  6. 6.
    Rauf, Abdur, Muhammad Imran, Masood Sadiq Butt, Muhammad Nadeem, Dennis G. Peters, and Mohammad S. Mubarak. 2018. Resveratrol as an anti-cancer agent: a review. Critical Reviews in Food Science and Nutrition.  https://doi.org/10.1080/10408398.2016.1263597.PubMedCrossRefGoogle Scholar
  7. 7.
    Corrêa, M.G., P.R. Pires, F.V. Ribeiro, S.Z. Pimentel, R.C.V. Casarin, F.R. Cirano, H.T. Tenenbaum, and M.Z. Casati. 2017. Systemic treatment with resveratrol and/or curcumin reduces the progression of experimental periodontitis in rats. Journal of Periodontal Research.  https://doi.org/10.1111/jre.12382.PubMedCrossRefGoogle Scholar
  8. 8.
    Kim, Nayoung, Jin Myung Park, Sang Hyub Lee, Bo Hye Kim, Jun Hyuk Son, Ji Kon Ryu, Yong Tae Kim, and Woochang Lee. 2017. Effect of combinatory treatment with resveratrol and guggulsterone on mild acute pancreatitis in mice. Pancreas.  https://doi.org/10.1097/MPA.0000000000000763.PubMedCrossRefGoogle Scholar
  9. 9.
    Nunes, Sandra, Francesca Danesi, Daniele Del Rio, and Paula Silva. 2018. Resveratrol and inflammatory bowel disease: the evidence so far. Nutrition Research Reviews.  https://doi.org/10.1017/S095442241700021X.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Cottart, Charles Henry, Valérie Nivet-Antoine, Christelle Laguillier-Morizot, and Jean Louis Beaudeux. 2010. Resveratrol bioavailability and toxicity in humans. Molecular Nutrition & Food Research.  https://doi.org/10.1002/mnfr.200900437.CrossRefGoogle Scholar
  11. 11.
    Walle, Thomas, Faye Hsieh, Mark H. DeLegge, John E. Oatis, and U. Kristina Walle. 2004. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metabolism and Disposition.  https://doi.org/10.1124/dmd.104.000885.PubMedCrossRefGoogle Scholar
  12. 12.
    Amiot, Marie Josephe, Beatrice Romier, Thi Mai Anh Dao, Raphaelle Fanciullino, Joseph Ciccolini, Remy Burcelin, Laurent Pechere, Claude Emond, Jean François Savouret, and Eric Seree. 2013. Optimization of trans-Resveratrol bioavailability for human therapy. Biochimie.  https://doi.org/10.1016/j.biochi.2013.01.008.PubMedCrossRefGoogle Scholar
  13. 13.
    Santos, Ana Cláudia, Francisco Veiga, and António J. Ribeiro. 2011. New delivery systems to improve the bioavailability of resveratrol. Expert Opinion on Drug Delivery.  https://doi.org/10.1517/17425247.2011.581655.PubMedCrossRefGoogle Scholar
  14. 14.
    Sohail, Muhammad, Allah Rakha, Masood Sadiq Butt, Muhammad Jawad Iqbal, and Summer Rashid. 2017. Rice bran nutraceutics: a comprehensive review. Critical Reviews in Food Science and Nutrition.  https://doi.org/10.1080/10408398.2016.1164120.CrossRefGoogle Scholar
  15. 15.
    Ahmed, Bulbul, Siqin Liu, and Hongwei Si. 2016. Antiadipogenic effects and mechanisms of combinations of genistein, epigallocatechin-3-gallate, and/or resveratrol in preadipocytes. Journal of Medicinal Food.  https://doi.org/10.1089/jmf.2016.0115.PubMedCrossRefGoogle Scholar
  16. 16.
    Xu, Dandan, Ge Yu, Pinggen Xi, Xiangyu Kong, Qi Wang, Lingwang Gao, and Zide Jiang. 2018. Synergistic effects of resveratrol and pyrimethanil against Botrytis cinerea on grape. Molecules.  https://doi.org/10.3390/molecules23061455.PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Qureshi, A. Asaf, Dilshad A. Khan, Wajiha Mahjabeen, Christopher J. Papasian, and Nilofer Qureshi. 2013. Nutritional supplement-5 with a combination of proteasome inhibitors (resveratrol, quercetin, δ-tocotrienol) modulate age-associated biomarkers and cardiovascular lipid parameters in human subjects. Journal of clinical & experimental cardiology.  https://doi.org/10.4172/2155-9880.1000238.
  18. 18.
    Noben, Cindy, Myrthe van Vilsteren, Cécile Boot, Romy Steenbeek, Dirkjan van Schaardenburg, Johannes R. Anema, Silvia Evers, Frans Nijhuis, and Angelique de Rijk. 2017. Economic evaluation of an intervention program with the aim to improve at-work productivity for workers with rheumatoid arthritis. Journal of Occupational Health.  https://doi.org/10.1539/joh.16-0082-OA.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Alvan, Gunnar, Erik Berninger, Lars L. Gustafsson, Kjell K. Karlsson, Gilles Paintaud, and Monique Wakelkamp. 2017. Concentration–response relationship of hearing impairment caused by quinine and salicylate: pharmacological similarities but different molecular mechanisms. Basic & Clinical Pharmacology & Toxicology.  https://doi.org/10.1111/bcpt.12640.CrossRefGoogle Scholar
  20. 20.
    Souto, A.A., M.C. Carneiro, M. Seferin, M.J.H. Senna, A. Conz, and K. Gobbi. 2001. Determination of trans-resveratrol concentrations in Brazilian red wines by HPLC. Journal of Food Composition and Analysis.  https://doi.org/10.1006/jfca.2000.0970.CrossRefGoogle Scholar
  21. 21.
    Bernardi, A., A.A.C.C.V. Zilberstein, E. Jäger, M.M. Campos, F.B. Morrone, J.B. Calixto, A.R. Pohlmann, S.S. Guterres, and A.M.O. Battastini. 2009. Effects of indomethacin-loaded nanocapsules in experimental models of inflammation in rats. British Journal of Pharmacology.  https://doi.org/10.1111/j.1476-5381.2009.00244.x.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Zhang, Junqiang, Xianbin Song, Wei Cao, Jinseng Lu, Xiaoqing Wang, Gaoyuan Wang, Zhicheng Wang, and Xiaoyu Chen. 2016. Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with resveratrol. Scientific Reports.  https://doi.org/10.1038/srep32928.
  23. 23.
    Wei, Yulong, Jie Jia, Xin Jin, Wei Tong, and Hongtao Tian. 2018. Resveratrol ameliorates inflammatory damage and protects against osteoarthritis in a rat model of osteoarthritis. Molecular Medicine Reports.  https://doi.org/10.3892/mmr.2017.8036.
  24. 24.
    Yang, Guliang, Chia Che Chang, Yiwen Yang, Li Yuan, Leishiyuan Xu, Chi Tang Ho, and Shiming Li. 2018. Resveratrol alleviates rheumatoid arthritis via reducing ROS and inflammation, inhibiting MAPK signaling pathways, and suppressing angiogenesis. Journal of Agricultural and Food Chemistry.  https://doi.org/10.1021/acs.jafc.8b05047.PubMedCrossRefGoogle Scholar
  25. 25.
    Ramalingam, Prakash, and Young Tag Ko. 2016. Validated LC-MS/MS method for simultaneous quantification of resveratrol levels in mouse plasma and brain and its application to pharmacokinetic and brain distribution studies. Journal of Pharmaceutical and Biomedical Analysis.  https://doi.org/10.1016/j.jpba.2015.11.026.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Muzzio, Miguel, Zhihua Huang, Shu Chieh Hu, William D. Johnson, David L. McCormick, and Izet M. Kapetanovic. 2012. Determination of resveratrol and its sulfate and glucuronide metabolites in plasma by LC-MS/MS and their pharmacokinetics in dogs. Journal of Pharmaceutical and Biomedical Analysis.  https://doi.org/10.1016/j.jpba.2011.10.023.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Elmali, N., I. Esenkaya, A. Harma, K. Ertem, Y. Turkoz, and B. Mizrak. 2005. Effect of resveratrol in experimental osteoarthritis in rabbits. Inflammation Research.  https://doi.org/10.1007/s00011-004-1341-6.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Müller, C.R., S.R. Schaffazick, A.R. Pohlmann, L. De Lucca Freitas, N. Pesce Da Silveira, T. Dalla Costa, and S.S. Guterres. 2001. Spray-dried diclofenac-loaded poly(ε-caprolactone) nanocapsules and nanospheres. Preparation and physicochemical characterization. Pharmazie 56 (11): 864–867.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Pham-Marcou, Thi Aurore, Hélène Beloeil, Xueging Sun, Marc Gentili, Djouer Yaici, Gérard Benoit, Dan Benhamou, and Jean Xavier Mazoit. 2008. Antinociceptive effect of resveratrol in carrageenan-evoked hyperalgesia in rats: prolonged effect related to COX-2 expression impairment. Pain.  https://doi.org/10.1016/j.pain.2008.08.010.PubMedCrossRefGoogle Scholar
  30. 30.
    Gentilli, Marc, Jean Xavier Mazoit, Hervé Bouaziz, Dominique Fletcher, Robert F. Casper, Dan Benhamou, and Jean François Savouret. 2001. Resveratrol decreases hyperalgesia induced by carrageenan in the rat hind paw. Life Sciences.  https://doi.org/10.1016/S0024-3205(00)01018-3.PubMedCrossRefGoogle Scholar
  31. 31.
    Esposito, E., D. Impellizzeri, G. Bruschetta, M. Cordaro, R. Siracusa, E. Gugliandolo, R. Crupi, and S. Cuzzocrea. 2016. A new co-micronized composite containing palmitoylethanolamide and polydatin shows superior oral efficacy compared to their association in a rat paw model of carrageenan-induced inflammation. European Journal of Pharmacology.  https://doi.org/10.1016/j.ejphar.2016.03.033.PubMedCrossRefGoogle Scholar
  32. 32.
    Pokkanta, Piramon, Phumon Sookwong, Manatchanok Tanang, Saranya Setchaiyan, Pittayaporn Boontakham, and Sugunya Mahatheeranont. 2019. Simultaneous determination of tocols, γ-oryzanols, phytosterols, squalene, cholecalciferol and phylloquinone in rice bran and vegetable oil samples. Food Chemistry.  https://doi.org/10.1016/j.foodchem.2018.07.225.PubMedCrossRefGoogle Scholar
  33. 33.
    Kobayashi, Eri, Junya Ito, Shunji Kato, Kazue Sawada, Midori Matsuki, Hiroyuki Hashimoto, Teruo Miyazawa, and Kiyotaka Nakagawa. 2016. Presence of orally administered rice bran oil γ-oryzanol in its intact form in mouse plasma. Food & Function.  https://doi.org/10.1039/c6fo01552b.CrossRefGoogle Scholar
  34. 34.
    Rao, Y.P.C., D. Sugasini, and B.R. Lokesh. 2016. Dietary gamma oryzanol plays a significant role in the anti-inflammatory activity of rice bran oil by decreasing pro-inflammatory mediators secreted by peritoneal macrophages of rats. Biochemical and Biophysical Research Communications.  https://doi.org/10.1016/j.bbrc.2016.09.140.PubMedCrossRefGoogle Scholar
  35. 35.
    Van Le, H., D.V. Nguyen, Q. Vu Nguyen, B.S. Malau-Aduli, P.D. Nichols, and A.E.O. Malau-Aduli. 2019. Fatty acid profiles of muscle, liver, heart and kidney of Australian prime lambs fed different polyunsaturated fatty acids enriched pellets in a feedlot system. Scientific Reports 9: 1–11.  https://doi.org/10.1038/s41598-018-37956-y.CrossRefGoogle Scholar
  36. 36.
    Impellizzeri, Daniela, Elena Talero, Rosalba Siracusa, Antonio Alcaide, Marika Cordaro, Jose Maria Zubelia, Giuseppe Bruschetta, et al. 2015. Protective effect of polyphenols in an inflammatory process associated with experimental pulmonary fibrosis in mice. The British Journal of Nutrition.  https://doi.org/10.1017/s0007114515002597.PubMedCrossRefGoogle Scholar
  37. 37.
    Mamadou, G., C. Charrueau, J. Dairou, N. Limas Nzouzi, B. Eto, and G. Ponchel. 2017. Increased intestinal permeation and modulation of presystemic metabolism of resveratrol formulated into self-emulsifying drug delivery systems. International Journal of Pharmaceutics.  https://doi.org/10.1016/j.ijpharm.2017.02.036.PubMedCrossRefGoogle Scholar
  38. 38.
    Chang, Chih Wei, Cheng Yu Wong, Yu Tse Wu, and Mei Chich Hsu. 2017. Development of a solid dispersion system for improving the oral bioavailability of resveratrol in rats. European Journal of Drug Metabolism and Pharmacokinetics 42: 239–249.  https://doi.org/10.1007/s13318-016-0339-0.CrossRefPubMedGoogle Scholar
  39. 39.
    Elmali, N., O. Baysal, A. Harma, I. Esenkaya, and B. Mizrak. 2006. Effects of resveratrol in inflammatory arthritis. Inflammation.  https://doi.org/10.1007/s10753-006-9012-0.CrossRefGoogle Scholar
  40. 40.
    Xuzhu, G., Mousa Komai-Koma, Bernard P. Leung, Hwee Siew Howe, Charles McSharry, Iain B. McInnes, and Xu. Damo. 2012. Resveratrol modulates murine collagen-induced arthritis by inhibiting Th17 and B-cell function. Annals of the Rheumatic Diseases.  https://doi.org/10.1136/ard.2011.149831.PubMedCrossRefGoogle Scholar
  41. 41.
    Malaguarnera, Lucia. 2019. Influence of Resveratrol on the immune response. Nutrients.  https://doi.org/10.3390/nu11050946.PubMedCentralCrossRefPubMedGoogle Scholar
  42. 42.
    Zaky, Amira, Ahmad Bassiouny, Mahitab Farghaly, and Bassma M. El-Sabaa. 2017. A combination of resveratrol and curcumin is effective against aluminum chloride-induced neuroinflammation in rats. Journal of Alzheimer's Disease.  https://doi.org/10.3233/JAD-161115.PubMedCrossRefGoogle Scholar
  43. 43.
    Ferraresi, Alessandra, Suratchanee Phadngam, Federica Morani, Alessandra Galetto, Oscar Alabiso, Giovanna Chiorino, and Ciro Isidoro. 2017. Resveratrol inhibits IL-6-induced ovarian cancer cell migration through epigenetic up-regulation of autophagy. Molecular Carcinogenesis.  https://doi.org/10.1002/mc.22582.PubMedCrossRefGoogle Scholar
  44. 44.
    Schwager, Joseph, Nathalie Richard, Christoph Riegger, and Norman Salem. 2015. ω -3 PUFAs and resveratrol differently modulate acute and chronic inflammatory processes. BioMed Research International.  https://doi.org/10.1155/2015/535189.CrossRefGoogle Scholar
  45. 45.
    Sarkar, S., S. Mazumder, S.J. Saha, and U. Bandyopadhyay. 2016. Management of inflammation by natural polyphenols: a comprehensive mechanistic update. Current Medicinal Chemistry 23 (16): 1657–1695.PubMedCrossRefGoogle Scholar
  46. 46.
    Bozimowski, Gregory. 2015. A review of nonsteroidal anti-inflammatory drugs. AANA Journal 83 (6): 425–433.PubMedGoogle Scholar
  47. 47.
    Kutil, Zsofia, Veronika Temml, David Maghradze, Marie Pribylova, Marcela Dvorakova, Daniela Schuster, Tomas Vanek, and Premysl Landa. 2014. Impact of wines and wine constituents on cyclooxygenase-1, cyclooxygenase-2, and 5-lipoxygenase catalytic activity. Mediators of Inflammation.  https://doi.org/10.1155/2014/178931.CrossRefGoogle Scholar
  48. 48.
    Zhang, Heng, Hao Yan, Xiaoliang Zhou, Huaqing Wang, Yiling Yang, Junling Zhang, and Hui Wang. 2017. The protective effects of resveratrol against radiation-induced intestinal injury. BMC Complementary and Alternative Medicine 17: 1–8.  https://doi.org/10.1186/s12906-017-1915-9.CrossRefGoogle Scholar
  49. 49.
    Symington, Burger, Rudo F. Mapanga, Gavin R. Norton, and M. Faadiel Essop. 2017. Resveratrol co-treatment attenuates the effects of HIV protease inhibitors on rat body weight and enhances cardiac mitochondrial respiration. PLoS One.  https://doi.org/10.1371/journal.pone.0170344.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Escola de Ciências da Saúde e da Vida, Centro de Pesquisa em Toxicologia e FarmacologiaPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil
  2. 2.Fundação Oswaldo Cruz, Instituto Oswaldo CruzRio de JaneiroBrazil
  3. 3.Escola de Ciências da Saúde e da Vida, Laboratório de Farmacologia AplicadaPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil
  4. 4.Escola de Ciências da Saúde e da Vida, Programa de Pós-Graduação em Biologia Celular e MolecularPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil

Personalised recommendations