Inflammation

, Volume 37, Issue 6, pp 2139–2155 | Cite as

Improvement of Bioavailability and Anti-Inflammatory Potential of Curcumin in Combination with Emu Oil

  • Manish Kumar Jeengar
  • Shweta Shrivastava
  • Kala Nair
  • Sreenivasa Reddy Singareddy
  • Uday Kumar Putcha
  • M. V. N. Kumar Talluri
  • V. G. M. Naidu
  • Ramakrishna Sistla
Article

Abstract

The purpose of the present study is to evaluate the effect of emu oil on bioavailability of curcumin when co-administered and to evaluate the property that enhances the anti-inflammatory potential of curcumin. Oral bioavailability of curcumin in combination with emu oil was determined by measuring the plasma concentration of curcumin by HPLC. The anti-inflammatory potential was evaluated in carrageenan-induced paw edema model (acute model) and in Freund’s complete adjuvant (FCA)-induced arthritis model (chronic model) in male SD rats. The anti-inflammatory potential of curcumin in combination with emu oil has been significantly increased in both acute and chronic inflammatory models as evident from inhibition of increase in paw volume, arthritic score, and expression of pro-inflammatory cytokines. The increased anti-inflammatory activity in combination therapy is due to enhanced bioavailability (5.2-fold compared to aqueous suspension) of curcumin by emu oil. Finally, it is concluded that the combination of emu oil with curcumin will be a promising approach for the treatment of arthritis.

KEY WORDS

emu oil curcumin bioavailability arthritis Freund’s adjuvant 

Notes

Acknowledgments

MKJ, SS, KN, MVNKT, and VGMN thank Department of Pharmaceuticals, Ministry of Chemical and Fertilizers, Government of India and Project Director, NIPER Hyderabad. RS thanks Director, IICT for encouragement. We thank Dr. Sarath Chandra Mouli Veeravalli, Rheumatologist for radiological scoring of X-Ray images. Part of this work was supported by CSC 0111 grant of CSIR-IICT.

References

  1. 1.
    Heller, A., T. Koch, J. Schmeck, and K. van Ackern. 1998. Lipid mediators in inflammatory disorders. Drugs 55: 487–496.PubMedCrossRefGoogle Scholar
  2. 2.
    Payne, R. 2000. Limitations of NSAIDs for pain management: Toxicity or lack of efficacy? The Journal of Pain 1: 14–18.PubMedCrossRefGoogle Scholar
  3. 3.
    Adams, M.J. 2006. Interactive effects of dietary resistant starch and fish oil on short-chain fatty acid production and agonist-induced contractility in ileum of young rats. Digestive Diseases and Sciences 51: 254–261.PubMedCrossRefGoogle Scholar
  4. 4.
    Topping, D.L., and P.M. Clifton. 2001. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiological Reviews 81: 1031–1064.PubMedGoogle Scholar
  5. 5.
    Aggarwal, B.B., and K.B. Harikumar. 2009. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. The International Journal of Biochemistry & Cell Biology 41: 40–59.CrossRefGoogle Scholar
  6. 6.
    Aggarwal, B.B., and B. Sung. 2009. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends in Pharmacological Sciences 30: 85–94.PubMedCrossRefGoogle Scholar
  7. 7.
    Aggarwal, B.B., Sundaram, C., Malani, N., Ichikawa, H. 2007. Curcumin:the Indian solid gold. Advances in Experimental Medicine and Biology 595: 1–75.Google Scholar
  8. 8.
    Anand, P., A.B.. Kunnumakkara, R.A. Newman, and B.B. Aggarwal. 2007. Bioavailability of curcumin: problems and promises. Molecular Pharmaceutics 4: 807–818.Google Scholar
  9. 9.
    Paradkar, A., A.A. Ambike, B.K. Jadhav, and K.R. Mahadik. 2004. Characterization of curcumin-PVP solid dispersion obtained by spray drying. International Journal of Pharmaceutics 271: 281–286.PubMedCrossRefGoogle Scholar
  10. 10.
    Saw, C.L.L., Y. Huang, and A.-N. Kong. 2010. Synergistic anti-inflammatory effects of low doses of curcumin in combination with polyunsaturated fatty acids: docosahexaenoic acid or eicosapentaenoic acid. Biochemical Pharmacology 79: 421–430.PubMedCrossRefGoogle Scholar
  11. 11.
    Jeengar, M., P. Kumar, D. Thummuri, S. Shrivastava, L. Guntuku, S. Ramakrishna, et al. 2014. Review on emu products for use as complementary and alternative medicine. Nutrition. doi:10.1016/j.nut.2014.04.004.Google Scholar
  12. 12.
    Chakrabarti, P.P., and R.B.N. Prasad. 2013. Isolation and Characterization of Oil from Fatty Tissues of Emu Birds Farmed in India. Journal of Lipid Science and Technology 45: 13–19.Google Scholar
  13. 13.
    Abimosleh Suzanne, M., D. Tran Cuong, and Gordon S. Howarth. 2013. Emu oil reduces small intestinal inflammation in the absence of clinical improvement in a rat model of Indomethacin-induced enteropathy. Evidence-Based Complementary and Alternative Medicine 2013: 10.Google Scholar
  14. 14.
    Joe, B., and B.R. Lokesh. 1997. Prophylactic and therapeutic effects of n-3 polyunsaturated fatty acids, capsaicin, and curcumin on adjuvant induced arthritis in rats. The Journal of Nutritional Biochemistry 8: 397–407.CrossRefGoogle Scholar
  15. 15.
    Simopoulos, A.P. 2002. Omega-3 fatty acids in inflammation and autoimmune diseases. Journal of the American College of Nutrition 21: 495–505.PubMedCrossRefGoogle Scholar
  16. 16.
    Kong, W., J.-H. Yen, E. Vassiliou, S. Adhikary, M.G. Toscano, and D. Ganea. 2010. Docosahexaenoic acid prevents dendritic cell maturation and in vitro and in vivo expression of the IL-12 cytokine family. Lipids in Health and Disease 9: 12.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Calder, P.C. 2006. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. The American Journal of Clinical Nutrition 83: S1505–S1519.Google Scholar
  18. 18.
    Maheshwari, M. 2010. Comparative bioavailability of curcumin, turmeric and Biocurcumaxâ„¢ in traditional vehicles using non-everted rat intestinal sac model. Journal of Functional Foods 2: 60–65.CrossRefGoogle Scholar
  19. 19.
    Ruan, L.P., S. Chen, B.Y. Yu, D.N. Zhu, G.A. Cordell, and S.X. Qiu. 2006. Prediction of human absorption of natural compounds by the non-everted rat intestinal sac model. European Journal of Medicinal Chemistry 41: 605–610.PubMedCrossRefGoogle Scholar
  20. 20.
    Ramshankar, Y.V., and S. Suresh. 2009. A sensitive reversed phase HPLC method for the determination of curcumin. Pharmacognosy Magazine 5: 71.Google Scholar
  21. 21.
    Morris CJ. 2003. Carrageenan-induced paw edema in the rat and mouse. Methods in Molecular Biology 225: 115–121.Google Scholar
  22. 22.
    Kuncha, M., V.G.M. Naidu, B.D. Sahu, S.G. Gadepalli, and R. Sistla. 2014. Curcumin potentiates the anti-arthritic effect of prednisolone in Freund's complete adjuvant-induced arthritic rats. Journal of Pharmacy and Pharmacology 66(1): 133–144.PubMedCrossRefGoogle Scholar
  23. 23.
    Naidu, V.G.M., K.R. Dinesh Babu, M.M. Thwin, R.L. Satish, P.V. Kumar, and P. Gopalakrishnakone. 2013. RANKL targeted peptides inhibit osteoclastogenesis and attenuate adjuvant induced arthritis by inhibiting NF-κB activation and down regulating inflammatory cytokines. Chemico-Biological Interactions 203: 467–479.PubMedCrossRefGoogle Scholar
  24. 24.
    Ohkawa, H., N. Ohishi, and K. Yagi. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry 95: 351–358.PubMedCrossRefGoogle Scholar
  25. 25.
    Uma Mahesh, B., S. Shrivastava, M. Kuncha, B.D. Sahu, C.V. Swamy, R.R. Pragada, et al. 2013. Ethanolic extract of Boswellia ovalifoliolata bark and leaf attenuates doxorubicin-induced cardiotoxicity in mice. Environmental Toxicology and Pharmacology 36: 840–849.PubMedCrossRefGoogle Scholar
  26. 26.
    Aebi, H. 1984. Catalase in vitro. Methods in Enzymology 105: 121–126.PubMedCrossRefGoogle Scholar
  27. 27.
    Bradley, P.P., D.A. Priebat, R.D. Christensen, and G. Rothstein. 1982. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. Journal of Investigative Dermatology 78: 206–209.PubMedCrossRefGoogle Scholar
  28. 28.
    Xia, Y., and J.L. Zweier. 1997. Measurement of myeloperoxidase in leukocyte-containing tissues. Analytical Biochemistry 245: 93–96.PubMedCrossRefGoogle Scholar
  29. 29.
    Bhutani, M.K., M. Bishnoi, and S.K. Kulkarni. 2009. Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes. Pharmacology Biochemistry and Behavior 92: 39–43.CrossRefGoogle Scholar
  30. 30.
    Kurzrock R, Li L. 2005. Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis, J Clin Oncol (Meeting Abstracts) 23.Google Scholar
  31. 31.
    Shaikh, J., D.D. Ankola, V. Beniwal, D. Singh, and M.N.V. Kumar. 2009. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. European Journal of Pharmaceutical Sciences 37: 223–230.PubMedCrossRefGoogle Scholar
  32. 32.
    Gupta, N., and N. Aggarwal. 2008. Bioavailability enhancement and targeting of stomach tumors using gastro-retentive floating drug delivery system of curcumin - "a technical note". AAPS PharmSciTech 9: 810–813.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Liu, A., H. Lou, L. Zhao, and P. Fan. 2006. Validated LC/MS/MS assay for curcumin and tetrahydrocurcumin in rat plasma and application to pharmacokinetic study of phospholipid complex of curcumin. Journal of Pharmaceutical and Biomedical Analysis 40: 720–727.PubMedCrossRefGoogle Scholar
  34. 34.
    Cui, J., B. Yu, Y. Zhao, W. Zhu, H. Li, H. Lou, et al. 2009. Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems. International Journal of Pharmaceutics 371: 148–155.PubMedCrossRefGoogle Scholar
  35. 35.
    Yadav, V.R., S. Suresh, K. Devi, and S. Yadav. 2009. Novel formulation of solid lipid microparticles of curcumin for anti-angiogenic and anti-inflammatory activity for optimization of therapy of inflammatory bowel disease. Journal of Pharmacy and Pharmacology 61: 311–321.PubMedCrossRefGoogle Scholar
  36. 36.
    Singh, R.B., M.A. Niaz, S. Ghosh, R. Beegom, V. Rastogi, J.P. Sharma, et al. 1996. Association of trans fatty acids (vegetable ghee) and clarified butter (Indian ghee) intake with higher risk of coronary artery disease in rural and urban populations with low fat consumption. International Journal of Cardiology 56: 289–298.PubMedCrossRefGoogle Scholar
  37. 37.
    Jacobson, M. 1987. Cholesterol oxides in Indian ghee: possible cause of unexplained high risk of atherosclerosis in Indian immigrant populations. The Lancet 330: 656–658.CrossRefGoogle Scholar
  38. 38.
    Wilson, T.A., R.J. Nicolosi, G. Handelman, S. Yoganathan, T. Kotyla, F. Orthoefer, et al. 2004. Comparative effects of emu and olive oil on aortic early atherosclerosis and associated risk factors in hypercholesterolemic hamsters. Nutrition Research 24: 395–406.CrossRefGoogle Scholar
  39. 39.
    Fukushima, M., T. Ohashi, M. Sekikawa, and M. Nakano. 1999. Comparative hypocholesterolemic effects of five animal oils in cholesterol-fed rats. Bioscience, Biotechnology, and Biochemistry 63: 202–205.PubMedCrossRefGoogle Scholar
  40. 40.
    Lindsay, R.J., M.S. Geier, R. Yazbeck, R.N. Butler, and G.S. Howarth. 2010. Orally administered emu oil decreases acute inflammation and alters selected small intestinal parameters in a rat model of mucositis. British Journal of Nutrition 104: 513.PubMedCrossRefGoogle Scholar
  41. 41.
    Joe, B., M.M. Griffiths, E.F. Remmers, and R.L. Wilder. 1999. Animal models of rheumatoid arthritis and related inflammation. Current Rheumatology Reports 1: 139–148.PubMedCrossRefGoogle Scholar
  42. 42.
    Bevaart, L., M.J. Vervoordeldonk, and P.P. Tak. 2010. Evaluation of therapeutic targets in animal models of arthritis: how does it relate to rheumatoid arthritis? Arthritis and Rheumatism 62: 2192–2205.PubMedCrossRefGoogle Scholar
  43. 43.
    Pragasam, S.J., V. Murunikkara, E.P. Sabina, and M. Rasool. 2013. Ameliorative effect of p-coumaric acid, a common dietary phenol, on adjuvant-induced arthritis in rats. Rheumatology International 33: 325–334.PubMedCrossRefGoogle Scholar
  44. 44.
    Somasundaram, S., J. Sadique, and A. Subramoniam. 1983. In vitro absorption of [14C] leucine during inflammation and the effect of antiinflammatory drugs in the jejunum of rats. Biochemical Medicine 29: 259–264.PubMedCrossRefGoogle Scholar
  45. 45.
    Achliya, G.S., S.G. Wadodkar, and A.K. Dorle. 2004. Evaluation of hepatoprotective effect of Amalkadi Ghrita against carbon tetrachloride-induced hepatic damage in rats. Journal of Ethnopharmacology 90: 229–232.PubMedCrossRefGoogle Scholar
  46. 46.
    Rehman, Q., and N.E. Lane. 2001. Bone loss. Therapeutic approaches for preventing bone loss in inflammatory arthritis. Arthritis Research 3: 221–227.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Nanke, Y., S. Kotake, H. Akama, and N. Kamatani. 2002. Alkaline phosphatase in rheumatoid arthritis patients: possible contribution of bone-type ALP to the raised activities of ALP in rheumatoid arthritis patients. Clinical Rheumatology 21: 198–202.PubMedCrossRefGoogle Scholar
  48. 48.
    Kataoka, H., S. Horiyama, M. Yamaki, H. Oku, K. Ishiguro, T. Katagi, et al. 2002. Anti-inflammatory and anti-allergic activities of hydroxylamine and related compounds. Biological and Pharmaceutical Bulletin 25: 1436–1441.PubMedCrossRefGoogle Scholar
  49. 49.
    Yamaguchi Y, Tanaka Y, Yamada K, Band ô Y. 1989. Kunitomo M. Abnormal lipid metabolism in adjuvant arthritic rats. Japanese Journal of Pharmacology 50:377–386.Google Scholar
  50. 50.
    Heliovaara, M., K. Aho, P. Knekt, A. Reunamen, and A. Aromaa. 1996. Serum cholesterol and risk of rheumatoid arthritis in a cohort of 52,800 men and women. Rheumatology 35: 255–257.CrossRefGoogle Scholar
  51. 51.
    Mishra, K.K., H.P. Pandey, and R.H. Singh. 2007. A clinical study on cortisol and certain metabolites in some chronic psychosomatic disorders. Indian Journal of Clinical Biochemistry 22: 41–43.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Kim, M., and Y. Kim. 2010. Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase in rats fed a high fat diet. Nutrition Research and Practice 4: 191–195.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Babu, P.S., and K. Srinivasan. 1997. Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma longa) in streptozotocin induced diabetic rats. Molecular and Cellular Biochemistry 166: 169–175.PubMedCrossRefGoogle Scholar
  54. 54.
    Bauerova, K., S. Poništ, D. Mihalová, F. Dráfi, and V. Kuncírová. 2011. Utilization of adjuvant arthritis model for evaluation of new approaches in rheumatoid arthritis therapy focused on regulation of immune processes and oxidative stress. Interdisciplinary Toxicology 4(1): 33–39.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Sotnikova, R., S. Ponist, J. Navarova, D. Mihalova, V. Tomekova, M. Strosova, et al. 2009. Effects of sesame oil in the model of adjuvant arthritis. Neuroendocrinology Letters 30: 22.PubMedGoogle Scholar
  56. 56.
    Kamanli, A., M. Nazıroğlu, N. Aydılek, and C. Hacıevlıyagil. 2004. Plasma lipid peroxidation and antioxidant levels in patients with rheumatoid arthritis. Cell Biochemistry and Function 22: 53–57.PubMedCrossRefGoogle Scholar
  57. 57.
    Hassan, M.Q., R.A. Hadi, Z.S. Al-Rawi, V.A. Padron, and S.J. Stohs. 2001. The glutathione defense system in the pathogenesis of rheumatoid arthritis. Journal of Applied Toxicology 21: 69–73.PubMedCrossRefGoogle Scholar
  58. 58.
    Balasubramanayam, M., A. Adaikala Koteswari, R. Sampath Kumar, S. Finny Monickaraj, J. Uma Maheswari, and V. Mohan. 2003. Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications. Journal of Biosciences 28: 715–721.CrossRefGoogle Scholar
  59. 59.
    Jackson, J.K., T. Higo, W.L. Hunter, and H.M. Burt. 2006. The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis. Inflammation Research 55: 168–175.PubMedCrossRefGoogle Scholar
  60. 60.
    Bennett, D.C., W.E. Code, D.V. Godin, and K.M. Cheng. 2008. Comparison of the antioxidant properties of emu oil with other avian oils. Animal Production Science 48: 1345–1350.CrossRefGoogle Scholar
  61. 61.
    Mullane, K.M., R. Kraemer, and B. Smith. 1985. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemie myocardium. Journal of Pharmacological Methods 14: 157–167.PubMedCrossRefGoogle Scholar
  62. 62.
    Ukil, A., S. Maity, S. Karmakar, N. Datta, J.R. Vedasiromoni, and P.K. Das. 2003. Curcumin, the major component of food flavour turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-induced colitis. British Journal of Pharmacology 139: 209–218.PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Szekanecz, Z., M.M. Halloran, M.V. Volin, J.M. Woods, R.M. Strieter, G.K. Haines, et al. 2000. Temporal expression of inflammatory cytokines and chemokines in rat adjuvant-induced arthritis. Arthritis & Rheumatism 43: 1266–1277.CrossRefGoogle Scholar
  64. 64.
    Koenders, M.I., E. Lubberts, B. Oppers-Walgreen, L. van den Bersselaar, M.M. Helsen, F.E. Di Padova, et al. 2005. Blocking of interleukin-17 during reactivation of experimental arthritis prevents joint inflammation and bone erosion by decreasing RANKL and interleukin-1. The American Journal of Pathology 167: 141–149.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Goldring, S.R. 2003. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology (Oxford, England) 42: ii11–ii16.CrossRefGoogle Scholar
  66. 66.
    Shanahan, J.C., L.W. Moreland, and R.H. Carter. 2003. Upcoming biologic agents for the treatment of rheumatic diseases. Current Opinion in Rheumatology 15: 226–263.PubMedCrossRefGoogle Scholar
  67. 67.
    Deng, G.-M., L. Zheng, F.K.-M. Chan, and M. Lenardo. 2005. Amelioration of inflammatory arthritis by targeting the pre-ligand assembly domain of tumor necrosis factor receptors. Nature Medicine 11: 1066–1072.PubMedCrossRefGoogle Scholar
  68. 68.
    Bharti, A.C., Y. Takada, and B.B. Aggarwal. 2004. Curcumin (diferuloylmethane) inhibits receptor activator of NF-κB ligand-induced NF-κB activation in osteoclast precursors and suppresses osteoclastogenesis. The Journal of Immunology 172: 5940–5947.PubMedCrossRefGoogle Scholar
  69. 69.
    Shishodia, S., G. Sethi, and B.B. Aggarwal. 2005. Curcumin: getting back to the roots. Annals of the New York Academy of Sciences 1056: 206–217.PubMedCrossRefGoogle Scholar
  70. 70.
    Yoganathan, S., R. Nicolosi, T. Wilson, G. Handelman, P. Scollin, R. Tao, et al. 2003. Antagonism of croton oil inflammation by topical emu oil in CD-1 mice. Lipids 38: 603–607.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Manish Kumar Jeengar
    • 1
  • Shweta Shrivastava
    • 1
  • Kala Nair
    • 1
  • Sreenivasa Reddy Singareddy
    • 3
  • Uday Kumar Putcha
    • 3
  • M. V. N. Kumar Talluri
    • 1
  • V. G. M. Naidu
    • 1
  • Ramakrishna Sistla
    • 2
  1. 1.National Institute of Pharmaceutical Education & ResearchHyderabadIndia
  2. 2.Medicinal Chemistry and Pharmacology DivisionIndian Institute of Chemical TechnologyHyderabadIndia
  3. 3.National Institute of NutritionHyderabadIndia

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