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http://dx.doi.org/10.4062/biomolther.2016.052

Restoration of Declined Immune Responses and Hyperlipidemia by Rubus occidenalis in Diet-Induced Obese Mice  

Lee, Youngjoo (College of Pharmacy, Sahmyook University)
Kim, Jiyeon (College of Pharmacy, Sahmyook University)
An, Jinho (College of Pharmacy, Sahmyook University)
Lee, Sungwon (College of Pharmacy, Sahmyook University)
Lee, Heetae (College of Pharmacy, Sahmyook University)
Kong, Hyunseok (College of Pharmacy, Sahmyook University)
Song, Youngcheon (College of Pharmacy, Sahmyook University)
Choi, Hye Ran (Berry and Biofood Research Institute)
Kwon, Ji-Wung (Berry and Biofood Research Institute)
Shin, Daekeun (Berry and Biofood Research Institute)
Lee, Chong-Kil (College of Pharmacy, Chungbuk National University)
Kim, Kyungjae (College of Pharmacy, Sahmyook University)
Publication Information
Biomolecules & Therapeutics / v.25, no.2, 2017 , pp. 140-148 More about this Journal
Abstract
Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor $(TNF)-{\alpha}$ level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline.
Keywords
Rubus occidentalis; Hyperlipidemia; Immune restoration; In vivo CTL assay;
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Times Cited By KSCI : 6  (Citation Analysis)
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1 Lee, J. E., Park, E., Lee, J. E., Auh, J. H., Choi, H. K., Lee, J., Cho, S. and Kim, J. H. (2011) Effects of a Rubus coreanus Miquel supplement on plasma antioxidant capacity in healthy Korean men. Nutr. Res. Pract. 5, 429-434.   DOI
2 Lee, M. J., Lee, S. J., Choi, H. R., Lee, J. H., Kwon, J. W., Chae, K. S., Jeong, J. T. and Lee, T. B. (2014b) Improvement of cholesterol and blood pressure in fruit, leaf and stem extracts from black raspberry in vitro. Korean J. Med. Crop. Sci. 22, 177-187.   DOI
3 Lei, L., Li, H., Yan, F. and Xiao, Y. (2013) Hyperlipidemia impaired innate immune response to periodontal pathogen porphyromonas gingivalis in apolipoprotein E knockout mice. PLoS One. 8, e71849.   DOI
4 Ludewig, B., Jaggi, M., Dumrese, T., Brduscha-Riem, K., Odermatt, B., Hengartner, H. and Zinkernagel, R. M. (2001) Hypercholesterolemia exacerbates virus-induced immunopathologic liver disease via suppression of antiviral cytotoxic T cell responses. J. Immunol. 166, 3369-3376.   DOI
5 Lumeng, C. N. and Saltiel, A. R. (2011) Inflammatory links between obesity and metabolic disease. J. Clin. Invest. 121, 2111-2117.   DOI
6 Nam, M. K., Choi, H. R., Cho, J. S., Cho, S. M., Ha, K. C., Kim, T. H., Ryu, H. Y. and Lee, Y. I. (2014) Inhibitory effects of Rubi Fructus extracts on hepatic steatosis development in high-fat diet-induced obese mice. Mol. Med. Rep. 10, 1821-1827.   DOI
7 Pope, C. R. (1991) Pathology of lymphoid organs with emphasis on immunosuppression. Vet. Immunol. Immunopathol. 30, 31-44.   DOI
8 Bhandary, B., Lee, G. H., Marahatta, A., Lee, H. Y., Kim, S. Y., So, B. O., Kwon, J. W., Song, J. Y., Lee, H. K., Kim, H. R., Chae, S. W. and Chae H. J. (2012) Water extracts of immature Rubus coreanus regulate lipid metabolism in liver cells. Biol. Pharm. Bull. 35, 1907-1913.   DOI
9 Okla, M., Kang, I., Kim da, M., Gourineni, V., Shay, N., Gu, L. and Chung, S. (2015) Ellagic acid modulates lipid accumulation in primary human adipocytes and human hepatoma Huh7 cells via discrete mechanisms. J. Nutr. Biochem. 26, 82-90.   DOI
10 Popa, C., Netea, M. G., van Riel, P. L., van der Meer, J. W. and Stalenhoef, A. F. (2007) The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism and cardiovascular risk. J. Lipid Res. 48, 751-762.   DOI
11 Saleem, A., Husheem, M., Härkönen, P. and Pihlaja, K. (2002) Inhibition of cancer cell growth by crude extract and the phenolics of Terminalia chebutaretz. fruit. J. Ethnopharmacol. 81, 327-336.   DOI
12 Sato Mito, N., Suzui, M., Yoshino, H., Kaburagi, T. and Sato, K. (2009) Long term effects of high fat and sucrose diets on obesity and lymphocyte proliferation in mice. J. Nutr. Health Aging 13, 602-606.   DOI
13 Seeram, N. P., Adams, L. S., Henning, S. M., Niu, Y., Zhang, Y., Nair, M. G. and Heber, D. (2005) In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegrante juice. J. Nutr. Biochem. 16, 360-367.   DOI
14 van Diepen, J. A., Berbée, J. F., Havekes, L. M. and Rensen, P. C. (2013) Interactions between inflammation and lipid metabolism: Relevance for efficacy of anti-inflammatory drugs in the treatment of atherosclerosis. Atherosclerosis 228, 306-315.   DOI
15 Emanuela, F., Grazia, M., Marco de, R., Maria Paola, L., Giorgio, F. and Marco, B. (2012) Inflammation as a Link between Obesity and Metabolic Syndrome. J. Nutr. Metab. 2012, 476380.
16 Bradley, J. R. (2008) TNF-mediated inflammatory disease. J. Pathol. 214, 149-160.   DOI
17 Cha, H. S., Park, M. S. and Park, K. M. (2001) Physiological activities of Rubus coreanus Miquel. Korean J. Food Sci. Technol. 33, 409-415.
18 Choi, H. R., Lee, S. J., Lee, J. H., Kwon, J. W., Lee, H. K., Jeong, J. T. and Lee, T. B. (2013) Cholesterol-lowering effects of unripe black raspberry water extract. J. Korean Soc. Food Sci. Nutr. 42, 1899-1907.   DOI
19 Feingold, K. R. and Grunfeld, C. (1992) Role of cytokines in inducing hyperlipidemia. Diabetes 41 Suppl 2, 97-101.   DOI
20 Geerlings, S. E. and Hoepelman, A. I. (1999) Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol. Med. Microbiol. 26, 259-265.   DOI
21 Gottschlich, M. M., Mayes, T., Khoury, J. C. and Warden, G. D. (1993) Significance of obesity on nutritional, immunologic, hormonal, and clinical outcome parameters in burns. J. Am. Diet. Assoc. 93, 1261-1268.   DOI
22 Yoon, I., Wee, J. H., Moon, J. H., Ahn, T. H. and Park, K. H. (2003) Isolation and identification of quercetin with antioxidative activity from the fruits of Rubus coreanum Miquel. Korean J. Food Sci. Technol. 35, 499-502.
23 Im, S. A., Lee, Y. R., Lee, Y. H., Lee, M. K., Park, Y. I., Lee, S., Kim, K. and Lee, C. K. (2010) In vivo evidence of the immunomodulatory activity of orally administered Aloe vera gel. Arch. Pharm. Res. 33, 451-456.   DOI
24 Jeong, M. Y., Kim, H. L., Park, J., Jung, Y., Youn, D. H., Lee, J. H., Jin, J. S., So, H. S., Park, R., Kim, S. H., Kim, S. J., Hong, S. H. and Um, J. Y. (2015) Rubi Fructus (Rubus coreanus) activates the expression of thermogenic genes in vivo and in vitro. Int. J. Obes. (Lond). 39, 456-464.   DOI
25 Winer, D. A., Winer, S., Shen, L., Wadia, P. P., Yantha, J., Paltser, G., Tsui, H., Wu, P., Davidson, M. G., Alonso, M. N., Leong, H. X., Glassford, A., Caimol, M., Kenkel, J. A., Tedder, T. F., McLaughlin, T., Miklos, D. B., Dosch, H. M. and Engleman, E. G. (2011) B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat. Med. 17, 610-617.   DOI
26 Wisse, B. E. (2004) The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J. Am. Soc. Nephrol. 15, 2792-2800.   DOI
27 Yang, H., Youm, Y. H., Vandanmagsar, B., Rood, J., Kumar, K. G., Butler, A. A. and Dixit, V. D. (2009) Obesity accelerates thymic aging. Blood 114, 3803-3812.   DOI
28 Yoshimura, Y., Nishii, S., Zaima, N., Moriyama, T. and Kawamura, Y. (2013) Ellagic acid improves hepatic steatosis and serum lipid composition through reduction of serum resistin levels and transcriptional activation of hepatic ppara in obese, diabetic KK-A(y) mice. Biochem. Biophys. Res. Commun. 434, 486-491.   DOI
29 Lee, J. E., Cho, S. M., Park, E., Lee, S. M., Kim, Y., Auh, J. H., Choi, H. K., Lim, S., Lee, S. C. and Kim, J. H. (2014a) Anti-inflammatory effects of Rubus coreanus Miquel through inhibition of NF-${\kappa}B$ and MAP Kinase. Nutr. Res. Pract. 8, 501-508.   DOI
30 Kim, Y. J., Han, S. H., Jeon, J. Y., Hwang, M. H., Im, Y. J., Chae, S. W. and Kim, M. G. (2012) Method development of ellagic acid as marker compound for standardization of gochangbokbunja (Rubus coreanus Miquel) as functional ingredient. J. Korean Soc. Food Sci. Nutr. 41, 1554-1558.   DOI