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American Journal of Medical and Biological Research. 2015, 3(6), 139-145
DOI: 10.12691/ajmbr-3-6-1
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Impact of Nigella Sativa, Omega-3 Fatty Acids and Chromium Picolinate on NF-κB /leptin-insulin Axis in Obese Subjects with Non-alcoholic Fatty Liver Disease

Noha M. Shafik1, Reham A. Mariah1, 2, Hussam Baghdadi2, Sherine Ragab Shafik3, Loai Mohammed El-Ahwal4, Salah Mohamed El Sayed2, 5, and Nassar Ayoub Abdellatif Omar6

1Departments of Medical Biochemistry, Faculty of Medicine, Tanta University, Egypt

2Department of Clinical Biochemistry and Molecular Medicine, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia

3Ph.D in Medical Biochemistry, Faculty of Medicine, Tanta University, Egypt

4Department of Internal Medicine, Faculty of Medicine, Tanta University, Egypt

5Department of Medical Biochemistry, Sohag Faculty of Medicine, Sohag University, Egypt

6Department of Anatomy, Faculty of Medicine, Sohag University, Egypt

Pub. Date: November 17, 2015

Cite this paper:
Noha M. Shafik, Reham A. Mariah, Hussam Baghdadi, Sherine Ragab Shafik, Loai Mohammed El-Ahwal, Salah Mohamed El Sayed and Nassar Ayoub Abdellatif Omar. Impact of Nigella Sativa, Omega-3 Fatty Acids and Chromium Picolinate on NF-κB /leptin-insulin Axis in Obese Subjects with Non-alcoholic Fatty Liver Disease. American Journal of Medical and Biological Research. 2015; 3(6):139-145. doi: 10.12691/ajmbr-3-6-1


Background: The global problem of obesity epidemic involves an increased risk of non-alcoholic fatty liver disease (NAFLD) whereby oxidative stress induces fibrogenesis. Objectives: to assess the coordinated impact of obesity management strategy on nuclear factor kappa beta/p65 mRNA expression and biochemical parameters of oxidative stress, glycemic status and adipokines. Subjects and methods: This study was carried out on 60 subjects classified into, 15 normal healthy controls (group І) and 45 obese subjects who were divided equally into three groups: obese subjects with NAFLD (group ІІ), obese subjects who received natural product supplements (nigella sativa, green tea andchromium picolinate) (groupІІІ),obese subjects who received omega-3 fatty acids (group ІV) andthose who received caloric restricted diet (CRD) and exercise for 6 months. All groups were subjected to measurement of body mass index, waist to hip ratio (WHR), spectrophotometric measurement of serum levels of glucose, malondialdehyde (MDA) and total antioxidant capacity (AOC%), NF-κB /P65 subunit expression levels by real time-PCR in peripheral bloodmononuclear cells, estimation of levels of insulin, insulin like growth factor-1, leptin, adiponectin, fibronectin and oxidized LDL by enzyme linked immunosorbent assays. Results: There was a significant decrease inNF-κB/p65 mRNA expression in peripheral blood mononuclear cells, reduction in the levels of oxLDL, decreased insulin resistance and decreased leptin resistance which might be linked to hypoadiponectinemia. Levels of (AOC %) were significantly elevated after treatment. This was evident alongside reduction of BMI, WHR and fibrogenic potential in NAFLD. Conclusion: natural product supplements, CRD and exercise ameliorated the fibrogenic and atherogenic consequences of immune-inflammatory and oxidative stress-induced pathological mechanisms associated with obesity.

non-alcoholic fatty liver disease NF-κB/p65 nigella sativa chromiumpicolinate omega-3 fatty acids

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[1]  Sakaguchi S, Takahashi S, Sasaki T, Kumagai T, Nagata K. Progression of alcoholic and non-alcoholic steatohepatitis: common metabolic aspects of innate immune system and oxidative stress. Drug Metab Pharmacokinet. 2011; 26(1):30-46.
[2]  Gaudio E, Nobili V, Franchitto A, Onori P, Carpino G. Non-alcoholic fatty liver disease and atherosclerosis. Intern Emerg Med. 2012; 3:S297-305.
[3]  Sookoian S, Gianotti TF, Rosselli MS, Burgueño AL, Castaño GO, Pirola CJ. Liver transcriptional profile of atherosclerosis-related genes in human non-alcoholic fatty liver disease. Atherosclerosis. 2011; 218(2):378-85.
[4]  Sáinz N, González-Navarro CJ, Martínez JA, Moreno-Aliaga MJ. Leptin signaling as a therapeutic target of obesity.Expert Opin Ther Targets. 2015;1:1-17.
[5]  Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010; 72:219-46.
[6]  Samuel VT, Shulman GI. Mechanisms for insulin resistance: common threads and missing links. Cell. 2012; 148(5):852-71.
[7]  Paolisso G, Ammendola S, Del Buono A, Gambardella A, Riondino M, Tagliamonte MR,et al. Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function. J Clin Endocrinol Metab. 1997; 82(7):2204-9.
[8]  Lashinger LM, Ford NA, Hursting SD. Interacting inflammatory and growth factor signals underlie the obesity-cancer link. J Nutr. 2014; 144(2):109-13.
[9]  Tilg H, Moschen AR. Evolution of inflammation in non-alcoholic fatty liver disease: the multiple parallel hits hypothesis.Hepatology. 2010; 52(5):1836-46.
[10]  Marra F, Bertolani C. Adipokines in liver diseases. Hepatology. 2009; 50(3):957-69.
[11]  Van Loo G, Beyaert R. Negative regulation of NF-κB and its involvement in rheumatoid arthritis.Arthritis Res Ther. 2011;13(3):221.
[12]  Keys A, Fidanza F, Karvonen MJ, Kimura N, Taylor HL. Indices of relative weight and obesity. J Chronic Dis. 1972; 25(6):329-43.
[13]  Garrow JS, Webster J. Quetelet's index (W/H2) as a measure of fatness. Int J Obes. 1985; 9(2):147-53.
[14]  Trinder P. Determination of blood glucose using 4-amino phenazone as oxygen acceptor. J Clin Pathol. 1969; 22(2):246.
[15]  Fenzl A, Itariu BK, Kosi L, Fritzer-Szekeres M, Kautzky-Willer A, Stulnig TM, Kiefer FW. Circulating betatrophin correlates with atherogenic lipid profiles but not with glucose and insulin levels in insulin-resistant individuals.Diabetologia. 2014;57(6):1204-8.
[16]  Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC.Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.Diabetologia. 1985; 28(7):412-9.
[17]  Al Maskari MY, Alnaqdy AA. Correlation between Serum Leptin Levels, Body Mass Index and Obesity in Omanis. Sultan Qaboos Univ Med J.2006 ;6(2):27-31.
[18]  Robaczyk MG. Evaluation of leptin levels in plasma and their reliance on other hormonal factors affecting tissue fat levels in people with various levels of endogenous cotisol. Ann Acad Med Stetin. 2002; 48: 283-300.
[19]  Won WY, Lee CU, Chae JH, Kim JJ, Lee C, Kim DJ. Changes of plasma adiponectin levels after smoking cessation. Psychiatry Investig. 2014; 11(2):173-8.
[20]  Stubbs TM, Lazarchick J, horger EO. Plasmafibronectin levels in preclampsia. Am J obstetric Gynecol. 1984; 150:885-7.
[21]  Samani KG, Farrokhi E. Effects of cumin extract on oxLDL, paraoxanase-1 activity, FBS, total cholesterol, triglycerides, HDL-C, LDL-C, Apo A1, and Apo B in in the patients with hypercholesterolemia. Int J Health Sci (Qassim). 2014; 8(1):39-43.
[22]  Manuel PP, Miguel A. Spectrophotometric quantitation of antioxidant capacity through the formation of phosphomolybdenum complex: specific application to the determination of vitamin E. Analyt Biochem 1999; 259: 337-341.
[23]  Ohkawa, H., Ohishi, N., Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem.1979; 95: 351-358.
[24]  Slade HB, Greenwood JH, Hudson JL, Beekman RH 3rd, Riedy MC, Schwartz SA. Lymphocyte phenotyping of infants with congenital heart disease: comparison of cell preparation techniques. Digan Clin Immunol.1988; 5(5): 249-55
[25]  Sun W, Guo MM, Han P, Lin JZ, Liang FY, Tan GM, et al. Id-1 and p65 subunit of NF-kB promote migration of nasopharyngeal carcinoma cells and are correlated with poor prognosis. Carcinogenesis. 2012; 33(4):810-7.
[26]  Eslamparast T, Eghtesad S, Poustchi H, Hekmatdoost A. Recent advances in dietary supplementation, in treating non-alcoholic fatty liver disease.World J Hepatol. 2015; 7(2):204-12.
[27]  Gambino R, Musso G, Cassader M. Redox balance in the pathogenesis of non-alcoholic fatty liver disease: mechanisms and therapeutic opportunities. Antioxid Redox Signal. 2011; 15(5): 1325-65.
[28]  Levitan I, Volkov S, Subbaiah PV. Oxidized LDL: diversity, patterns of recognition, and pathophysiology.Antioxid Redox Signal. 2010; 13(1): 39-75.
[29]  Kynde I, Heitmann BL, Bygbjerg IC, Andersen LB, Helge JW. Hypoadiponectinemia in overweight children contributes to a negative metabolic risk profile 6 years later. Metabolism. 2009; 58(12): 1817-24.
[30]  Ley K, Miller YI, Hedrick CC. Monocyte and macrophage dynamics during atherogenesis. Arterioscler Thromb Vasc Biol. 2011; 31: 1506-1516.
[31]  Skoien R, Richardson MM, Jonsson JR, Powell EE, Brunt EM, Neuschwander-Tetri BA, et al. Heterogeneity of fibrosis patterns in non-alcoholic fatty liver disease supports the presence of multiple fibrogenic pathways. Liver Int. 2013; 33(4):624-32.
[32]  van der Meer AJ, Sonneveld M, Schouten JN, Janssen HL. [Reversibility of hepatic fibrosis]. Ned Tijdschr Geneeskd. 2014;158: A6790.
[33]  Hursting SD, Dunlap SM, Ford NA, Hursting MJ, Lashinger LM. Calorie restriction and cancer prevention: a mechanistic perspective.Cancer Metab. 2013; 1(1):10.
[34]  Hivert MF, Langlois MF, Carpentier AC.The entero-insular axis and adipose tissue-related factors in the prediction of weight gain in humans. Int J Obes (Lond). 2007 ; 31(5): 731-42.
[35]  Moyse E, Bédard K, Segura S, Mahaut S, Tardivel C, Ferland G,et al. Effects of aging and caloric restriction on brainstem satiety center signals in rats. Mech Ageing Dev. 2012; 133(2-3):83-91.
[36]  Han Y, Joe Y, Seo E, Lee SR, Park MK, Lee HJ, Kim DK.The hyperleptinemia and ObRb expression in hyperphagic obese rats. Biochem Biophys Res Commun. 2010; 394(1):70-4.
[37]  Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed. 2013; 3(5):337-52.
[38]  Ibrahim RM, Hamdan NS, Ismail M, Saini SM, Abd Rashid SN, Abd Latiff L, Mahmud R. Protective Effects of Nigella sativa on Metabolic Syndrome in Menopausal Women. Adv Pharm Bull. 2014; 4(1):29-33.
[39]  Sethi G, Ahn KS, Aggarwal BB. Targeting nuclear factor-kappa B activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosis. Mol Cancer Res. 2008; 6(6):1059-70.
[40]  Al-Suhaimi EA. Hepatoprotective and immunological functions of Nigella sativa seed oil against hypervitaminosis A in adult male rats. Int J Vitam Nutr Res. 2012; 82(4):288-97.
[41]  Sharma NK, Ahirwar D, Jhade D, Gupta S. Medicinal and Phamacological Potential of Nigella sativa: A Review. Ethnobotanical Review 13: 946-55, 2009.
[42]  Suksomboon N, Poolsup N, Yuwanakorn A. Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes. J Clin Pharm Ther. 2014; 39 (3): 292-306.
[43]  Chen WY, Chen CJ, Liu CH, Mao FC. Chromium attenuates high-fat diet-induced non-alcoholic fatty liver disease in KK/HlJ mice. Biochem Biophys Res Commun. 2010; 397(3): 459-64.
[44]  Heber D, Zhang Y, Yang J, Ma JE, Henning SM, Li Z. Green tea, black tea, and oolong tea polyphenols reduce visceral fat and inflammation in mice fed high-fat, high-sucrose obesogenic diets. J Nutr. 2014; 144(9):1385-93.
[45]  Xu Y, Zhang M, Wu T, Dai SXu J, Zhou Z. The anti-obesity effect of green tea polysaccharides, polyphenols and caffeine in rats fed with a high-fat diet. Food Funct. 2015; 6(1): 297-304.
[46]  López-Vicario C, Alcaraz-Quiles J, García-Alonso V, Rius B, Hwang SH, Titos E, et al. Inhibition of soluble epoxide hydrolase modulates inflammation and autophagy in obese adipose tissue and liver: role for omega-3 epoxides. Proc Natl Acad Sci U S A. 2015; 112(2): 536-41.
[47]  Simopoulos AP. Dietary omega-3 fatty acid deficiency and high fructose intake in the development of metabolic syndrome, brain metabolic abnormalities, and non-alcoholic fatty liver disease. Nutrients. 2013; 5(8):2901-23.
[48]  González-Périz A, Horrillo R, Ferré N, Gronert K, Dong B, Morán-Salvador E, et al. Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J. 2009; 23(6): 1946-57.
[49]  Tai CC, Ding ST. N-3 polyunsaturated fatty acids regulate lipid metabolism through several inflammation mediators: mechanisms and implications for obesity prevention. J Nutr Biochem. 2010; 21(5): 357-63.
[50]  Philp LK, Heilbronn LK, Janovska A, Wittert GA. Dietary enrichment with fish oil prevents high fat-induced metabolic dysfunction in skeletal muscle in mice. PLoS One. 2015; 10(2): e0117494.
[51]  Ding WJ, Wang Y, Fan JG. Regulation of adipokines by polyunsaturated fatty acids in a rat model of non-alcoholic steatohepatitis. Arch Iran Med. 2014; 17(8): 563-8.
[52]  Rafraf M, Mohammadi E, Asghari-Jafarabadi M, Farzadi L.Omega-3 fatty acids improve glucose metabolism without effects on obesity values and serum visfatin levels in women with polycystic ovary syndrome. J Am Coll Nutr. 2012; 31(5): 361-8.