Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Theracurmin (Highly Bioavailable Curcumin) Prevents High Fat Diet-Induced Hepatic Steatosis Development in Mice

  • Received : 2018.12.26
  • Accepted : 2019.03.08
  • Published : 2019.10.15
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Abstract

Curcumin, a hydrophobic polyphenol isolated from the Curcuma longa L. plant, has many pharmacological properties, including antioxidant, anti-inflammatory, and chemo-preventive activities. Curcumin has been shown to have potential in preventing nonalcoholic fatty liver disease (NAFLD). However, the low bioavailability of curcumin has proven to be a major limiting factor in its clinical adoption. Theracurmin, a highly bioavailable curcumin that utilizes micronized technology showed improved biological absorbability in vivo. The aim of this study was to investigate the role of theracurmin in modulating hepatic lipid metabolism in vivo. A fatty liver mouse model was produced by feeding mice a high fat diet (HFD; 60% fat) for 12 weeks. We found that treatment for 12 weeks with theracurmin significantly lowered plasma triacylglycerol (TG) levels and reduced HFD-induced liver fat accumulation. Theracurmin treatment lowered hepatic TG and total cholesterol (T-CHO) levels in HFD-fed mice compared to controls. In addition, theracurmin administration significantly reduced lipid peroxidation and cellular damage caused by reactive oxygen species in HFD-fed mice. Overall, these results suggest that theracurmin has the ability to control lipid metabolism and can potentially serve as an effective therapeutic remedy for the prevention of fatty liver.

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References

  1. Browning, J.D. and Horton, J.D. (2004) Molecular mediators of hepatic steatosis and liver injury. J. Clin. Invest., 114, 147-152. https://doi.org/10.1172/JCI200422422
  2. Friedman, S.L., Neuschwander-Tetri, B.A., Rinella, M. and Sanyal, A.J. (2018) Mechanisms of NAFLD development and therapeutic strategies. Nat. Med., 24, 908-922. https://doi.org/10.1038/s41591-018-0104-9
  3. Birkenfeld, A.L. and Shulman, G.I. (2014) Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes. Hepatology, 59, 713-723. https://doi.org/10.1002/hep.26672
  4. Marra, F., Gastaldelli, A., Svegliati Baroni, G., Tell, G. and Tiribelli, C. (2008) Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis. Trends Mol. Med., 14, 72-81. https://doi.org/10.1016/j.molmed.2007.12.003
  5. Kotronen, A. and Yki-Jarvinen, H. (2008) Fatty liver: a novel component of the metabolic syndrome. Arterioscler. Thromb. Vasc. Biol., 28, 27-38. https://doi.org/10.1161/ATVBAHA.107.147538
  6. Rinella, M.E. (2015) Nonalcoholic fatty liver disease: a systematic review. JAMA, 313, 2263-2273. https://doi.org/10.1001/jama.2015.5370
  7. Sunagawa, Y., Hirano, S., Katanasaka, Y., Miyazaki, Y., Funamoto, M., Okamura, N., Hojo, Y., Suzuki, H., Doi, O., Yokoji, T., Morimoto, E., Takahashi, T., Ozawa, H., Imaizumi, A., Ueno, M., Kakeya, H., Shimatsu, A., Wada, H., Hasegawa, K. and Morimoto, T. (2015) Colloidal submicron-particle curcumin exhibits high absorption efficiency-a double-blind, 3-way crossover study. J. Nutr. Sci. Vitaminol., 61, 37-44. https://doi.org/10.3177/jnsv.61.37
  8. Ohno, M., Nishida, A., Sugitani, Y., Nishino, K., Inatomi, O., Sugimoto, M., Kawahara, M. and Andoh, A. (2017) Nanoparticle curcumin ameliorates experimental colitis via modulation of gut microbiota and induction of regulatory T cells. PLoS ONE, 12, e0185999. https://doi.org/10.1371/journal.pone.0185999
  9. Farzaei, M.H., Zobeiri, M., Parvizi, F., El-Senduny, F.F., Marmouzi, I., Coy-Barrera, E., Naseri, R., Nabavi, S.M., Rahimi, R. and Abdollahi, M. (2018) Curcumin in liver diseases: a systematic review of the cellular mechanisms of oxidative stress and clinical perspective. Nutrients, 10, E855. https://doi.org/10.3390/nu10070855
  10. Maria, M., Eleni, P., George, V., Eftychia, T. and Constantinos, G. (2018) Effects of curcumin consumption on human chronic diseases: A narrative review of the most recent clinical data. Phytother. Res., 32, 957-975. https://doi.org/10.1002/ptr.6037
  11. Imaizumi, A. (2015) Highly bioavailable curcumin (Theracurmin): its development and clinical application. Pharma-Nutrition, 3, 123-130. https://doi.org/10.1016/j.phanu.2015.08.002
  12. Ding, L., Li, J., Song, B., Xiao, X., Zhang, B., Qi, M., Huang, W., Yang, L. and Wang, Z. (2016) Curcumin rescues high fat diet-induced obesity and insulin sensitivity in mice through regulating SREBP pathway. Toxicol. Appl. Pharmacol., 304, 99-109. https://doi.org/10.1016/j.taap.2016.05.011
  13. Shao, W., Yu, Z., Chiang, Y., Yang, Y., Chai, T., Foltz, W., Lu, H., Fantus, I.G. and Jin, T. (2012) Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. PLoS ONE, 7, e28784. https://doi.org/10.1371/journal.pone.0028784
  14. Sasaki, H., Sunagawa, Y., Takahashi, K., Imaizumi, A., Fukuda, H., Hashimoto, T., Wada, H., Katanasaka, Y., Kakeya, H., Fujita, M., Hasegawa, K. and Morimoto, T. (2011) Innovative preparation of curcumin for improved oral bioavailability. Biol. Pharm. Bull., 34, 660-665. https://doi.org/10.1248/bpb.34.660
  15. Cuomo, J., Appendino, G., Dern, A.S., Schneider, E., McKinnon, T.P., Brown, M.J., Togni, S. and Dixon, B.M. (2011) Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation. J. Nat. Prod., 74, 664-669. https://doi.org/10.1021/np1007262
  16. Gota, V.S., Maru, G.B., Soni, T.G., Gandhi, T.R., Kochar, N. and Agarwal, M.G. (2010) Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J. Agric. Food Chem., 58, 2095-2099. https://doi.org/10.1021/jf9024807
  17. Sunagawa, Y., Wada, H., Suzuki, H., Sasaki, H., Imaizumi, A., Fukuda, H., Hashimoto, T., Katanasaka, Y., Shimatsu, A., Kimura, T., Kakeya, H., Fujita, M., Hasegawa, K. and Morimoto, T. (2012) A novel drug delivery system of oral curcumin markedly improves efficacy of treatment for heart failure after myocardial infarction in rats. Biol. Pharm. Bull., 35, 139-144. https://doi.org/10.1248/bpb.35.139
  18. Cichoz-Lach, H. and Michalak, A. (2014) Oxidative stress as a crucial factor in liver diseases. World J. Gastroenterol., 20, 8082-8091. https://doi.org/10.3748/wjg.v20.i25.8082
  19. Oner-Iyidogan, Y., Kocak, H., Seyidhanoglu, M., Gurdol, F., Gulcubuk, A., Yildirim, F., Cevik, A. and Uysal, M. (2013) Curcumin prevents liver fat accumulation and serum fetuin-A increase in rats fed a high-fat diet. J. Physiol. Biochem., 69, 677-686. https://doi.org/10.1007/s13105-013-0244-9
  20. Liu, Y., Cheng, F., Luo, Y., Zhan, Z., Hu, P., Ren, H., Tang, H. and Peng, M. (2017) PEGylated curcumin derivative attenuates hepatic steatosis via CREB/PPAR-gamma/CD36 pathway. BioMed Res. Int., 2017, 8234507.
  21. Greenberg, A.S., Coleman, R.A., Kraemer, F.B., McManaman, J.L., Obin, M.S., Puri, V., Yan, Q.W., Miyoshi, H. and Mashek, D.G. (2011) The role of lipid droplets in metabolic disease in rodents and humans. J. Clin. Invest., 121, 2102-2110. https://doi.org/10.1172/JCI46069
  22. Ioannou, G.N. (2016) The role of cholesterol in the pathogenesis of NASH. Trends Endocrinol. Metab., 27, 84-95. https://doi.org/10.1016/j.tem.2015.11.008
  23. Walenbergh, S.M. and Shiri-Sverdlov, R. (2015) Cholesterol is a significant risk factor for non-alcoholic steatohepatitis. Expert Rev. Gastroenterol. Hepatol., 9, 1343-1346. https://doi.org/10.1586/17474124.2015.1092382
  24. Shimano, H. and Sato, R. (2017) SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology. Nat. Rev. Endocrinol., 13, 710-730. https://doi.org/10.1038/nrendo.2017.91
  25. Yang, J.W., Kim, H.S., Im, J.H., Kim, J.W., Jun, D.W., Lim, S.C., Lee, K., Choi, J.M., Kim, S.K. and Kang, K.W. (2016) GPR119: a promising target for nonalcoholic fatty liver disease. FASEB J., 30, 324-335. https://doi.org/10.1096/fj.15-273771
  26. Moore, K.J., Rayner, K.J., Suarez, Y. and Fernandez-Hernando, C. (2011) The role of microRNAs in cholesterol efflux and hepatic lipid metabolism. Annu. Rev. Nutr., 31, 49-63. https://doi.org/10.1146/annurev-nutr-081810-160756
  27. Tariq, Z., Green, C.J. and Hodson, L. (2014) Are oxidative stress mechanisms the common denominator in the progression from hepatic steatosis towards non-alcoholic steatohepatitis (NASH)? Liver Int., 34, e180-e190. https://doi.org/10.1111/liv.12523
  28. Rolo, A.P., Teodoro, J.S. and Palmeira, C.M. (2012) Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radic. Biol. Med., 52, 59-69. https://doi.org/10.1016/j.freeradbiomed.2011.10.003
  29. Spahis, S., Delvin, E., Borys, J.M. and Levy, E. (2017) oxidative stress as a critical factor in nonalcoholic fatty liver disease pathogenesis. Antioxid. Redox Signal., 26, 519-541. https://doi.org/10.1089/ars.2016.6776
  30. Negre-Salvayre, A., Auge, N., Ayala, V., Basaga, H., Boada, J., Brenke, R., Chapple, S., Cohen, G., Feher, J., Grune, T., Lengyel, G., Mann, G.E., Pamplona, R., Poli, G., Portero-Otin, M., Riahi, Y., Salvayre, R., Sasson, S., Serrano, J., Shamni, O., Siems, W., Siow, R.C.M., Wiswedel, I., Zarkovic, K. and Zarkovic, N. (2010) Pathological aspects of lipid peroxidation. Free Radic. Res., 44, 1125-1171. https://doi.org/10.3109/10715762.2010.498478
  31. Wei, Q.Y., Chen, W.F., Zhou, B., Yang, L. and Liu, Z.L. (2006) Inhibition of lipid peroxidation and protein oxidation in rat liver mitochondria by curcumin and its analogues. Biochim. Biophys. Acta, 1760, 70-77. https://doi.org/10.1016/j.bbagen.2005.09.008
  32. Scapagnini, G., Vasto, S., Abraham, N.G., Caruso, C., Zella, D. and Fabio, G. (2011) Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders. Mol. Neurobiol., 44, 192-201. https://doi.org/10.1007/s12035-011-8181-5
  33. Yang, C., Zhang, X., Fan, H. and Liu, Y. (2009) Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia. Brain Res., 1282, 133-141. https://doi.org/10.1016/j.brainres.2009.05.009
  34. He, H.-J., Wang, G.-Y., Gao, Y., Ling, W.-H., Yu, Z.-W. and Jin, T.-R. (2012) Curcumin attenuates Nrf2 signaling defect, oxidative stress in muscle and glucose intolerance in high fat diet-fed mice. World J. Diabetes, 3, 94. https://doi.org/10.4239/wjd.v3.i5.94