Red Yeast Rice Protects Hepatocytes conditions of Rats Receiving High Fat Diet

Doti Wahyuningsih, Helmin Elyani, Dini Sri Damayanti, Arif Yahya, Muhammad Zainal Fadli

Abstract


Triglyceride (TG) is a simple and the main lipid of the daily diet. Nowadays, TG is emerging as an independent risk factor for cardiovascular disease, and increasing clinical data that indicate a high level of this simple lipid in serum may alert and play a role in liver impairment. Red yeast rice (RYR) reduces serum TG in human and animals. The rice is widely used as a natural inhibitor of HMG-CoA reductase to correct serum cholesterol level. Bioactive components of the rice are well known to have antioxidant properties. This study examined whether RYR protects hepatocytes by evaluating the serum AST-ALT, HDL-Cholesterol (HDL-C), TG levels, and the number of liver foam cells in hypertriglyceridemic rats. Twenty male Wistar rats were grouped into 5. Four groups received a high-fat diet (HFD), 40 g/animal/day for 60 days to induce hypertriglyceridemic condition. Along with the HFD treatment, three groups received 108, 54, and 27 mg/kgBW/day of RYR, respectively. Two other groups received standard and only HFD diet, respectively. Intracardiac blood was collected for measuring AST and ALT using AST or ALT activity assay Kit, respectively, serum TG and HDL-C by Enzymatic Caloric Test.  Hematoxylin-Eosin–stained 4µmm thick slices of liver tissues were prepared to count foam cell number by a light microscope with 400x magnificence. Data were analyzed using the Kruskal Wallis continued by the Mann Whitney U test. The p values of < 0.05 were considered to be significant. The present study found that 108, 54, and 27 mg/kgBW/day of RYR significantly decreased serum TG, HDL-C, AST, and ALT compared with those of hypertriglyceridemic rats receiving no RYR. The decreasing levels of the parameters were in relation to the doses of RYR. The doses of 108 and 54 mg/kgBW/day resulted in complete recovery of the liver tissues suffered from steatosis (p < 0.05). The RYR dose of 108 mg/KgBW/day completely corrects the serum HDL-C level. In conclusion, red yeast rice may have a potency to protect hepatocytes injuries due to hypertriglyceridemia.

Keywords


Red yeast rice, foam cell, hypertriglyceridemia, AST-ALT

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References


Zhang XL, Wu LF, Wang YS et al. (2017) The protective effects of probiotic-fermented soymilk on high-fat diet-induced hyperlipidemia and liver injury. Journal of Functional Foods 30: 220 – 227. doi: 10.1016/j.jff.2017.01.002.

Svegliati-Baroni G, Saccomanno S, Rychlicki C et al. (2011) Glucagon-like peptide-1receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high-fat diet in nonalcoholic stea-tohepatitis. Liver International 31 (9): 1285 – 1297. doi: 10.1111/j.1478-3231.2011.02462.x.

Agrawal S, Duseja AK (2012) Non-alcoholic fatty liver disease: East versus west. Journal of Clinical and Experimental Hepatology 2 (2): 122 – 134. doi: 10.1016/S0973-6883(12)60101-7.

Aslam M, Aggarwal S, Sharma KK et al. (2016) Post-prandial hypertriglyceridemia predicts development of insulin resistance glucose intolerance and type 2 diabetes. PLoS ONE 11 (1): e0145730. doi: 10.1371/ jour-nal.pone.0145730.

Nordestgaard BG, Varbo A (2014) Triglycerides and cardiovascular disease. Lancet 384 (9943): 626 – 635. doi: 10.1016/S0140-6736(14)61177-6.

Gaggini M, Morelli M, Buzzigoli E et al. (2013) Non-Alcoholic Fatty Liver Disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients 5 (5): 1544 – 1560. doi: 10.3390/nu5051544.

Endo A (1979) Monacolin K, a new hypocholesterolemic agent produced by a Monascus species. Journal of Antibiotics 32 (8): 852 – 854. doi: 10.7164/antibiotics.32.852.

Yang CW, Mousa SA (2012) The effect of red yeast rice (Monascus purpureus) in dyslipidemia and other disorders. Complimentary Therapy in Medicine 20 (6): 466 – 474. doi: 10.1016/j.ctim.2012.07.004.

Lee CL, Kung YH, Wu CL et al. (2010) Monascin and ankaflavin act as novel hypolipidemic and high-density lipoprotein cholesterol-raising agents in red mold dioscorea. Journal of Agricultural and Food Chemistry 58 (16): 9013 – 9019. doi: 10.1021/jf101982v.

Li Y, Jiang L, Jia Z et al. (2014) A meta-analysis of red yeast rice: An effective and relatively safe alternative approach for dyslipidemia. PLoS ONE 9 (6): 1 – 10. doi: 10.1371/journal.pone.0098611

Zhao SP, Li R, Dai W et al. (2017) Xuezhikang contributes to greater triglyceride reduction than simvastatin in hypertriglyceridemia rats by up-regulating apolipoprotein A5 via the PPARα signaling pathway. PLoS ONE 12 (9): 1 - 12. doi: 10.1371/journal.pone.0184949.

Yan L, Yu CZ, Mei HY, Yang ZO (2012) Natural occurrence of citrinin in widely consumed traditional Chinese food red yeast rice, medicinal plants and their related products. Food Chemistry 132 (2): 1040 – 1045. doi: 10.1016/j.foodchem.2011.11.051.

Bovdisova I, Zbynovska K, Kalafova A, Capcarova M (2016) Toxicological properties of mycotoxin citrinin. Journal of Microbiology, Biotechnology and Food Sciences 5 (Special 1): 10 - 13. doi: 10.15414/jmbfs.2016.5.special1.10-13.

Pascual-Ahuir A, Vanacloig-Pedros E, Proft M (2014) Toxicity mechanisms of the food contaminant citrinin: Application of a quantitative yeast model. Nutrients 6 (5): 2077 – 2087. doi: 10.3390/nu6052077. 1.

Klimek M, Wang S, Ogunkanmi A (2009) Safety and efficacy of red yeast rice (Monacus purpureus) as an alternative therapy for hyperlipidemia. Pharmacy and Therapeutics 34 (6): 313 – 316.

Murwani S, Ali M, Muliartha A (2006) Atherogenic diet of white-rat (Rattus novergicus strain wistar) as atherosclerotic animal model. Jurnal Kedokteran Brawijaya 22 (1): 6 – 9. doi: 10.21776/ub.jkb.2006.022.01.2.

Anggraeni CD, Soebandono J, Kustiwinarni (2009) Pengaruh pemberian angkak terhadap kadar kolesterol total darah tikus putih (Rattus norvegicus). Cermin Dunia Kedokteran 36 (2): 94 – 95. doi: 10.22338/mka.v36.i1.p29-38.2012.

Auberval N, Dal S, Bietiger W et al. (2014) Metabolic and oxidative stress markers in Wistar rats after 2 months on a high-fat diet. Diabetology & Metabolic Syndrome 6: 130. doi: 10.1186/1758-5996-6-130.

Marquesa C, Meireles M, Norbertoa Set al. (2016) High-fat diet-induced obesity Rat model: a comparison between Wistar and Sprague-Dawley Rat. Adipocyte 5 (1): 11 – 21. doi: 10.1080/21623945.2015.1061723

Ramalho L, da Jornada MN, Antunes LC, Hidalgo MP (2017) Metabolic disturbances due to a high-fat diet in a non-insulin resistant animal model. Nutrition & Diabetes 7: 1 - 5 doi: 10.1038/nutd.2016.47.

Kleiner DE, Brunt EM (2012) Nonalcoholic fatty liver disease: Pathologic patterns and biopsy evaluation in clinical research. Seminars in Liver Disease 32 (1): 3 – 13. doi: 10.1055/s-0032-1306421.

Tannapfel A, Denk H, Dienes HP et al. (2011) Histo-pathological diagnosis of non-alcoholic and alcoholic fatty liver disease. Virchows Archv 458 (5): 511 – 523. doi: 10.1007/s00428-011-1066-1.

Takahashi Y, Fukusato T (2014) Histopathology of non-alcoholic fatty liver disease/nonalcoholic steatohepatitis. World Journal of Gastroenterology 20 (42): 15539 – 15548. doi: 10.1007/s00428-011-1066-1.

van Heek M, Farley C, Compton DS et al. (2000) Comparison of the activity and disposition of the novel cholesterol absorption inhibitor, SCH58235, and its glucuronide, SCH60663. British Journal of Pharmacology 129 (8): 1748 – 1754. doi: 10.1038/sj.bjp.0703235.

Rai AK, Debetto P, Sala FD (2013) Molecular regulation of cholesterol metabolism: HDL-based intervention through drugs and diets. Indian Journal of Experimental Biology 51 (11):885-894.

Pan X and Hussain MM (2012) Gut triglyceride production. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1821 (5): 727 – 735. doi: 10.1016/j.bbalip.2011.09.013.

Rohman A,Triyana K, Sismindari, Erwanto Y (2012) Differentiation of lard and other animal fats based on triacylglycerols composition and principal component analysis. International Food Research Journal 19 (2): 475 – 479.

Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B (2009) Role of bile acids and bile acid receptors in metabolic regulation. Physiological Reviews 89 (1): 147 – 191, 2009. doi: 10.1152/physrev.00010.2008.

Islam S, Fukiya S, Hagio M et al. (2011). Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology 141 (5): 1773 – 1781. doi: 10.1053/j.gastro.2011.07.046.

Yamada S, Kawaguchi H, Yamada T et al. (2017) Cholic acid enhances visceral adiposity, atherosclerosis and non-alcoholic fatty liver disease in microminipigs. Journal of Atherosclerosis and Thrombosis 24 (11): 1150 – 1166. doi: 10.5551/jat.39909.

de Aguiar Vallim TQ, Tarling EJ, Edwards PA (2013) Pleiotropic roles of bile acids in metabolism. Cell Metabolism 17 (5): 657 – 669. doi: 10.1016/j.cmet.2013.03.013.

Ando H, Tsuruoka S, Yamamoto H et al. (2005) Regulation of cholesterol 7alpha-hydroxylase mRNA expression in C57BL/6 mice fed an atherogenic diet. Atherosclerosis 178 (2): 265 – 269. doi: 10.1016/j.atherosclerosis.2004.09.016.

Vergnes L, Phan J, Strauss M et al. (2003) Cholesterol and cholate components of an atherogenic diet induce distinct stages of hepatic inflammatory gene expression. The Journal of Biological Chemistry 278: 42774 – 42784. doi: 10.1074/jbc.M306022200.

Papandreou D, Karabouta Z, Rousso I (2012) Are dietary cholesterol intake and serum cholesterol levels related to nonalcoholic fatty liver disease in obese children? Choles-terol 2012: 1 – 5. doi:10.1155/2012/572820

Kim WR, Flamm SL, Di Bisceglie AM, Bodenheimer, Jr HC (2008) Serum activity of Alanine Aminotransferase (ALT) as an indicator of health and disease. Hepatology 47 (4): 1363 – 1370. doi: 10.1002/hep.22109.

Tomizawa M, Kawanabe Y, Shinozaki F et al. (2014) Elevated levels of alanine transaminase and triglycerides within normal limits are associated with fatty liver. Experimental and Therapeutic Medicine 8 (3): 759 – 762. doi: 10.3892/etm.2014.1798.

Yao HR, Liu J, Plumeri D et al. (2011) Lipotoxicity in HepG2 cells triggered by free fatty acids. American Journal of Translational Research 3 (3): 284 – 291.

Musso G, Gambino R, Cassader M (2009) Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD). Progress in Lipid Research 48 (1): 1 – 26. doi: 10.1016/j.plipres.2008.08.001

Elyani H, Izzudin A, Rahmawati S (2014) Angkak 108 mg/KgBW is more potent to eeduced serum LDL and total cholesterol level than Simvastatin 0.01% in high fat diet rats. In Proceeding of Surabaya 1st International Symposium of Traditional complimentory and Alternative Medicine. 12th -13th April 2014.

Burg JS, Espenshade PJ (2011). Regulation of HMG-CoA reductase in mammals and yeast. Progress in Lipid Research 50 (4): 403 – 410. doi: 10.1016/j.plipres.2011.07.002.

Yii LL, Teng HW, Min HL, Nan WS (2008) Biologically active components and nutraceuticals in the monascus-fermented rice: A review. Applied Microbiology and Bio-technology 77 (5): 965 – 973. doi: 10. 1007/s00253-007-1256-6.

Reiner Z (2017) Hypertriglyceridaemia and risk of coro-nary artery disease. Nature Reviews Cardiology 14: 401 – 411. doi: 10.1038/nrcardio.2017.31.

Fazio S, Linton MF (2004) The Role of fibrates in managing hyperlipidemia: mechanisms of action and clinical efficacy. Current Atherosclerosis Reports 6 (2): 148 – 157. doi: 10.1007/s11883-004-0104-8.

Siquira Carvalho AA, Poti Lima ÜW, Valiente RA (2004) Statin and fibrate associated myopathy: Study of eight patients. Arquivos de Neuro-Psiquiatria 62 (2-A): 257 – 261. doi: 10.1590/S0004-282X2004000200013.

Liu J, Han L, Zhu L,Yu Y (2016) Free fatty acids, not triglycerides, are associated with non-alcoholic liver injury progression in high fat diet induced obese rats. Lipids in Health and Disease 15: 27. doi: 10.1186/s12944-016-0194-7.

Gupta M, Sasmal D, Bandyopadhyay S et al. (1983) Hematological changes produced in mice by ochratoxin A and citirinin. Toxicology 26 (1): 55 – 62. doi: 10.1016/0300-483X(83)90056-2.

Flajs D, Peraica M (2009) Toxicological properties of citrinin. Toxicological Properties of Citrinin 60 (4): 457 – 464. doi: 10.2478/10004-1254-60-2009-1992.

Shu PY, Lin CH (2002) Simple and sensitive determination of citrinin in Monascus by GC-selected ion monitor-ing mass spectrometry. Analytical Sciences 18 (3): 283 – 287. doi: 10.2116/analsci.18.283.

Patakova P (2013) Monascus secondary metabolites: production and biological activity. Journal of Industrial Microbiology & Biotechnology 40 (2): 169 – 181. doi: 10.1007/s10295-012-1216-8.

Lee BH, Hsu WH, Pan TM (2012) Red mold rice against hepatic inflammatory damage in Zn-deficient rats. Journal of Traditional and Complementary Medicine 2 (1): 52 – 60. doi: 10.1016/S2225-4110(16)30071-2.

Hsu YW, Hsu LC, Chang CL et al (2010) New anti-inflammatory and anti-proliferative constituents from fermented red mold rice Monascus purpureus NTU 568. Molecules 15 (11): 7815 – 7824. doi: 10.3390/molecules15117815.

Fitzgerald K, Redmond E, Harbor C (2012) Statin-induced Myopathy. Global Advances in Health and Medicine 1 (2): 32 – 36. doi: 10.7453/gahmj.2012.1.2.008.

Mueller PS (2006) Symptomatic myopathy due to red yeast rice. Annals of Internal Medicine 145 (6): 474 – 475. doi: 10.7326/0003-4819-145-6-200609190-00021.

Fung WT, Subramaniam G, Lee J et al. (2012) Assessment of extracts from red yeast r|ice for herb-drug interaction by in-vitro and in-vivo assays. Scientific Reports 2: 1 – 6. doi 10.1038/srep00298.

Aleo MD, Wyatt RD, Schnellmann RG (1991) The role of altered mitochondrial function in citrinin-induced toxicity to rat renal proximal tubule suspensions. Toxicology and Applied Pharmacology 109 (3): 455 – 463. doi: 10.1016/0041-008X(91)90008-3.




DOI: http://dx.doi.org/10.11594/jtls.09.02.06

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