Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
권호 표지
DOI QR코드

DOI QR Code

Protective Effect of Monascus pilosus Mycelial Extract on Hepatic Damage in High-Fat Diet Induced-obese Rats

고지방식이로 유도한 비만 흰쥐에서 Monascus pilosus 균사체 추출물의 간 손상 예방효과

  • Lee, Sang-Il (Department of Food, Nutrition and Culinary Arts, Keimyung College) ;
  • Kim, Jae-Won (Faculty of Food Science and Industrial Technology, Catholic University of Daegu) ;
  • Lee, Ye-Kyung (Division of Bioscience and Bioinformatics, Myongji University) ;
  • Yang, Seung-Hwan (Division of Bioscience and Bioinformatics, Myongji University) ;
  • Lee, In-Ae (Division of Bioscience and Bioinformatics, Myongji University) ;
  • Suh, Joo-Won (Division of Bioscience and Bioinformatics, Myongji University) ;
  • Kim, Soon-Dong (Division of Bioscience and Bioinformatics, Myongji University)
  • 이상일 (계명문화대학교 식품영양조리학부) ;
  • 김재원 (대구가톨릭대학교 외식식품산업학부) ;
  • 이예경 (명지대학교 생명과학정보학부) ;
  • 양승환 (명지대학교 생명과학정보학부) ;
  • 이인애 (명지대학교 생명과학정보학부) ;
  • 서주원 (명지대학교 생명과학정보학부) ;
  • 김순동 (명지대학교 생명과학정보학부)
  • Received : 2011.09.03
  • Accepted : 2011.09.07
  • Published : 2011.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Hepatoprotective effects of Monascus pilosus mycelial ethanol extract (MPME) were examined in high-fat diet induced-obese rats. The rats were randomly divided into 2 groups; normal control (NC) and a high-fat and high cholesterol diet group (HFC). The HFC diet group was fed a 5L79 diet supplemented with 15% lard and 1% cholesterol for 3 weeks for induction of obesity. And then, the rats were divided into 4 groups (n=5); the NC, a HFC diet obesity control group (HF), 0.5% MPME supplemented HFC diet group (MPM), and 2% conjugated linoleic acid (CLA) supplemented HFC diet group for 7 weeks. Whereas the daily weight gain of NC and HFC groups were 3.48 g and 4.48 g, respectively, those of MPM and CLA were 3.09 g and 4.38 g, respectively. Furthermore, activity of serum alanine and aspartic aminotransferase in HF was markedly higher than those of NC group, but, the activity in MPM and CLA was significantly lower than HF. Hepatic reduced glutathione content in MPM and CLA was higher than HF. On the contrary, hepatic lipid peroxide content in MPM and CLA was significantly lower than HF. In conclusion, although the precise mechanisms of the hepatoprotective effects of the MPME in this study are unknown, our study provides experimental evidence that MPME may prevent obesity and hepatic damage by high-fat and high cholesterol diet via inhibition of lipid absorption and induction of reactive oxygen spices scavenging enzyme such as superoxide dismutase.

본 연구는 Monascus pilosus mycelial ethanol extract (MPME)의 간 손상 예방 효과를 관찰할 목적으로 고지방-고콜레스테롤 식이로 유도한 비만 흰쥐(Sprague-Dawly계)를 대상으로 실험하였다. 실험동물은 정상 대조군(NC)과 고지방-고콜레스테롤 식이군(고지방식이군)으로 분류하였으며, 고지방식이군은 15% lard-1% cholesterol 첨가 5L79 diet로 3주간 성장시켜 비만을 유도한 후 고지방식이 대조군(HF), 0.5% MPME extract 첨가 고지방식이군(MPM) 및 2% CLA (conjugated linoleic acid) 첨가 고지방식이군(CLA)의 4개군 (n=5)으로 나누어 7주 동안 성장시켜 다음과 같은 결과를 얻었다. 1일 평균 체중증가량은 NC군은 3.48 g, HF군은 4.48 g인데 비하여 MPM군과 CLA군은 각각 3.09 g 및 4.38 g으로 HF군에 비하여 각각 31.03% 및 2.24%의 감소를 나타내었다. 체중에 대한 간 중량(%)은 모든 실험군에서 NC군에 비해 유의하게 증가하였으나 MPM군은 HF군에 비하여 유의하게 감소하였으며 CLA군은 HF군과의 차이를 보이지 않았다. 간 조직손상의 지표로 이용되는 혈청 ALT와 AST의 활성은 HF군에서는 NC군 보다 2.70배 및 2.55배가 각각 증가하였으며, CLA군은 NC군의 수준으로 회복되지는 못하였으나 HF군에 비해 현저히 감소하였고 MPM군에서는 정상상태인 NC군 수준으로 감소되었다. MPM군과 CLA군의 간조직 reduced glutathione의 함량은 HF군에 비해 높게 나타났으며, 이와 반대로 MPM 및 CLA군의 과산화지질 함량은 현저하게 낮았다. HF군의 간 조직 xanthine oxidoreductase (XOR)의 type O활성과 O/T ratio는 NC군에 비해 증가하였으며, MPM과 CLA군의 경우에는 HF군에 비해 감소하였다. 또한 HF군의 간 조직 superoxide dismutase (SOD) 및 glutathione Stransferase (GST)의 활성은 NC군에 비해 감소하였으나 MPM과 CLA군에서는 HF군에 비해 증가하였다. 이상의 결과를 종합해 볼 때, 본 실험의 결과로서는 MPME의 정확한 간 보호기전을 알 수가 없으나 MPME는 지방의 흡수를 억제함과 동시에 SOD와 같은 ROS 제거계 효소의 유도를 통하여 비만과 간 조직 손상을 예방하거나 경감시키는 효과가 있는 것으로 생각된다.

Keywords

References

  1. Aliciguzel Y, Ozen I, Aslan M, and Karayalcin U (2003) Activi-ties of xanthine oxidoreducatse and antioxidant enzymes in different tissues of diabetic rats. J Lab Clin Med 142, 172-177. https://doi.org/10.1016/S0022-2143(03)00110-0
  2. Birch AJ, Cassera A, Fitton P, Holker JSE, Smith H, Tompson GA, and Whalley WB (1962) Studies in relation to biosynthesis. Part XXX. Rotiorin, monascin and rubropunctatin. J Chem Soc 3583- 3587. https://doi.org/10.1039/jr9620003583
  3. Campos SC, Moreira DA, Nunes TD, Colepicolo P, and Brigagão MR (2005) Oxidative stress in alcohol-induced rat parotid sialadenosis. Arch Oral Biol 50, 661-668. https://doi.org/10.1016/j.archoralbio.2004.11.013
  4. Carmiel-Haggai M, Cederbaum AI, and Nieto N (2005) A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. FASEB J 19, 136-138.
  5. Chen WP, Ho BY, Lee CL, Lee CH, and Pan TM (2008) Red mold rice prevents the development of obesity, dyslipidemia and hyperinsulinemia induced by high-fat diet. Int J Obes (Lond) 32, 1694-1704. https://doi.org/10.1038/ijo.2008.156
  6. Choi MJ and Yu TS (2004) Effects of red-yeast-rice supplementation on bone mineral density and bone mineral content in overiectomized rats. Korean J Nutr 37, 423-430.
  7. Cornelli U (2009) Antioxidant use in nutraceuticals. Clin Dermatol 27, 175-194. https://doi.org/10.1016/j.clindermatol.2008.01.010
  8. DeLany JP, Blohm F, Truett AA, Scimeca JA, and West DB (1999) Conjugated linoliec acid rapidly reduces body fat content in mice without affecting energy intake. Am J Physiol 45, R1172-R1179.
  9. Duracková Z (2010) Some current insights into oxidative stress. Physiol Res 59, 459-469.
  10. Ellman GL (1959) Tissue sulfhydryl group. Arch Biochem Biophys 82, 70-77. https://doi.org/10.1016/0003-9861(59)90090-6
  11. Endo A (1979) Monacolin-K, a new hypocholesterolemic agent produced by Monascusspecies. J Antibiot (Tokyo) 32, 852-854. https://doi.org/10.7164/antibiotics.32.852
  12. Endo A (1980) Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. J Antibiot (Tokyo) 33, 334-336. https://doi.org/10.7164/antibiotics.33.334
  13. Eybl V, $ Kotyzov\acute{a}$ D, and $ Bludovská\acute{a}$ M (2004) The effect of curcumin on cadmium-induced oxidative damage and trace elements level in the liver of rats and mice. Toxicol Lett 151, 79-85. https://doi.org/10.1016/j.toxlet.2004.02.019
  14. Frank L (1991) Developmental aspects of experimental pulmonary oxygen toxicity. Free Radic Biol Med 11, 463-494. https://doi.org/10.1016/0891-5849(91)90062-8
  15. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, and Shimomura I (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114, 1752-1761. https://doi.org/10.1172/JCI21625
  16. Grundy SM (1998) Multi-factorial causation of obesity. Implications for prevention. Am J Clin Nutr 67, 563S-572S.
  17. Gutteridge JM and Swain J (1993) Lipoprotein oxidation. The 'fruit and vegetable gradient' and heart disease. Br J Biomed Sci 50, 284- 288.
  18. Gwinner W, Scheuer H, Haller H, Brandes RP, and Groene HJ (2006) Pivotal role of xanthine oxidase in the initiation of tubulointerstitial renal injury in rats with hyperlipidemia. Kidney Int 69, 481-487. https://doi.org/10.1038/sj.ki.5000121
  19. Habig WH, Pabst MJ, and Jacoby WB (1974) Glutathione Stransferase. The first enzymatic step in mercapuric acid formation. J Biol Chem 249, 7130-7139.
  20. Halliwell B (2009) The wanderings of a free radical. Free Radic Biol Med 46, 531-542. https://doi.org/10.1016/j.freeradbiomed.2008.11.008
  21. Hashim MS, Lincy S, Remya V, Teena M, and Anila L (2005) Effect of polyphenolic compounds from Coriandrum sati-vum on H2O2- induced oxidative stress in human lympho-cytes. Food Chem 92, 653-660. https://doi.org/10.1016/j.foodchem.2004.08.027
  22. Haumann BF (1996) Conjugated linoleic acid offers research promise. INFORM 7, 152-159.
  23. Hill JO, Lin D, Yakubu F, and Peters JC (1992) Development of dietary obesity in rats. Influence of amount andcomposition of dietary fat. Int J Obes Relat Metab Disord 16, 321-333.
  24. Im MJ, Manson PN, Bulkley GB, and Hoopes JE (1985) Effects of superoxide dismutase and allopurinol in survival of acute island skin flaps. Ann Surg 201, 357-359. https://doi.org/10.1097/00000658-198503000-00018
  25. Ip C and Scimeca JA (1997) Conjugated linoleic acid and linoleic acid are distinctive modulators of mammary carcinogenesis. Nutr Cancer 27, 131-135. https://doi.org/10.1080/01635589709514514
  26. Jakoby JB (1978) The glutathione S-transferase. A group of multifunctional detoxification proteins. Adv Enzymol Relat Areas Mol Biol 46, 383-414.
  27. Kang KJ, Kim KH, and Park HS (2002) Dietary conjugated linoleic acid did not affect on body fatness, fat cell size and leptin level in male Sprague Dawley rats. Nutr Sci (Korea) 5, 117-122.
  28. Kang MR, Kim JY, Hyun YJ, Kim HJ, Yeo HY, Song YD, and Lee JH (2008) The effect of red-yeast-rice supplement on serum lipid profile and glucose control in subjects with impaired fasting glucose or impaired glucose tolerance. Korean J Nutr 41, 31-40.
  29. Karmen A (1955) A note on the spectrophotometric assay of glutamicoxaloacetic transaminase in human blood serum. J Clin Invest 34, 131-133.
  30. Keisuke T, Tomio I, Nobukazu T, Hiroshi O, Shirou A, Shouichi T, and Yasue N (1992) Extraction of hypotensive substance from wheat benzi-koji. Nippon Shokuhin Kogyo Gakkaishi 39, 913-918. https://doi.org/10.3136/nskkk1962.39.913
  31. Kim EY and Rhyu MR (2008) Antimicrobial activities of Monascus Koji extracts. Korean J Food Sci Technol 40, 76-81.
  32. Kim JW, Kim SD, and Youn KS (2010) Effects of chicken treated with Hwangki-BeniKoji sauces on body weight, serum and hepatic lipid profiles of rats fed high fat and high cholesterol diets. J Korean Soc Food Sci Nutr 39, 1270-1278. https://doi.org/10.3746/jkfn.2010.39.9.1270
  33. Kiyoshi I, Yoshio M, Keisuke T, Nobukazu T, Sjpiocjo T, Sjorpi A, and Makoto T (1995) Effect of beni-koji extracts on blood pressure in primary hypertensive volunteers. Jpn J Nutr 53, 263- 271. https://doi.org/10.5264/eiyogakuzashi.53.263
  34. Kopelman PG (2000) Obesity as a medical problem. Nature 404, 635- 643.
  35. Lew EA (1985) Mortality and weight. Insured lives and the American Cancer Society studies. Ann Intern Med 103, 1024-1029. https://doi.org/10.7326/0003-4819-103-6-1024
  36. Lew EA (1985) Mortality and weight. Insured lives and the American Cancer Society studies. Ann Intern Med 103, 1024-1029. https://doi.org/10.7326/0003-4819-103-6-1024
  37. Ma JY, Li Y, Ye Q, Li J, Hua Y, Ju D, Zhang D, Cooper R, and Chang M (2000) Constituents of red yeast rice, a traditional Chinese food and medicine. J Agric Food Chem 48, 5220-5225. https://doi.org/10.1021/jf000338c
  38. Mantena SK, Vaughn DP, Andringa KK, Eccleston HB, King AL, Abrams GA, Doeller JE, Kraus DW, Darley-Usmar VM, and Bailey SM (2009) High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo. Biochem J 417, 183-193. https://doi.org/10.1042/BJ20080868
  39. Martin JP Jr, Dailey JM, and Sugarman E (1987) Negative and positive assays of superoxide dismutase based on hematoxylin autoxidation. Arch Biochem Biophys 255, 329-336. https://doi.org/10.1016/0003-9861(87)90400-0
  40. Martin JP Jr, Dailey JM, and Sugarman E (1987) Negative and positive assays of superoxide dismutase based on hematoxylin autoxidation. Arch Biochem Biophys 255, 329-336. https://doi.org/10.1016/0003-9861(87)90400-0
  41. Miller CC, Park Y, Pariza MW, and Cook ME (1994) Feeding conjugated linoleic acid to animals partially overcomes catabolic responses due to endotoxin injection. Biochem Biophys Res Commun 198, 1107-1112. https://doi.org/10.1006/bbrc.1994.1157
  42. Munday JS, Thompson KG, and James KA (1999) Dietary conjugated linoleic acids promote fatty streak formation in the C57BL/6 mouse atherosclerosis model. Br J Nutr 81, 251-255.
  43. Nohl H and Jordan W (1980) The metabolic fate of mitochondrial hydrogen peroxide. Eur J Biochem 111, 203-210.
  44. Oben JE, Enyegue DM, Fomekong GI, Soukontoua YB, and Agbor GA (2007) The effect of Cissus quadrangularis (CQR-300) and a Cissus formulation (CORE) on obesity and obesity-induced oxidative stress. Lipids Health Dis 6, 4.
  45. Oh JD, Yoon CG, and Yu TS (2004) Effect of dietary monascus koji on the liver damage induced by bromobenzene in rats. J Korean Soc Food Sci Nutr 33, 965-972. https://doi.org/10.3746/jkfn.2004.33.6.965
  46. Ohkawa H, Ohishi N, and Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95, 351-358. https://doi.org/10.1016/0003-2697(79)90738-3
  47. Park GY, Lee SJ, and Lim JG (1997) Effects of green tea catechin on cytochrome P450, xanthine oxidase activities in liver and liver damage in streptozotocin induced diabetic rats. J Korean Soc Food Sci Nutr 26, 901-907.
  48. Parks DA, Williams TK, and Beckman JS (1988) Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine. A reevaluation. Am J Physiol 254, G768-G774.
  49. Park Y, Albright KJ, Storkson JM, Liu W, Cook ME, and Pariza MW (1999) Changes in body composition in mice during feeding and withdrawal of conjugated linoleic acid. Lipids 34, 243-248. https://doi.org/10.1007/s11745-999-0359-7
  50. Reitman S and Frankel S (1957) A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28, 56-63.
  51. Rhyu MR, Kim EY, and Chung KS (2003) Effect of Monascus koji on the quality characteristics of bologna-type sausage. Korea J Food Sci Technol 35, 229-234.
  52. Sisk MB, Hausman DB, Martin RJ, and Azain MJ (2001) Dietary conjugated linoleic acid reduces adiposity in lean but not obese Zucker rats. J Nutr 131, 1668-1674.
  53. Stripe F and Della Corte E (1969) The regulation of rat liver xanthine oxidase. Conversion in vitro of the enzyme activity from dehydrogenase (type D) to oxidase (type O). J Biol Chem 244, 3855-3863.
  54. Valko M, Rhodes CJ, Moncol J, Izakovic M, and Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160, 1-40. https://doi.org/10.1016/j.cbi.2005.12.009
  55. Wang RS, Nakajima T, and Honma T (1999) Different change patterns of the isozymes of cytochrome P450 and glutathione Stransferases in chemically induced liver damage in rat. Ind Health 37, 440-448. https://doi.org/10.2486/indhealth.37.440
  56. Yasukawa K, Takahashi M, Yamanouchi S, and Takido M (1996) Inhibitory effect of oral administration of Monascus pigment on tumor promotion in two-stage carcinogenesis in mouse skin. Oncology 53, 247-249. https://doi.org/10.1159/000227568
  57. Yoon CG, Lee MK, and Lee SI (1998) Effect of growth on the enzyme activities of oxygen free radical generating and scavenging system in CCl4- treated rats. Korean J Gerontol 8, 35-42.
  58. Youn UK, Kim YH, and Kim SD (2003) Pigment and monacolin K content of beni-koji fermented with soybean curd residue. Korean J Food Preserv 10, 360-364.
  59. Yu TS, Kim HH, and Yoon CG (2003) Hepatic oxygen free radical metabolizing enzyme activities and serum lipid profile in rats fed diet supplemented with Monascus pigment. J Korean Soc Food Sci Nutr 33, 244-249.

Cited by

  1. Quality Characteristics and Content of Polysaccharides in Green Tea Fermented by Monascus pilosus vol.17, pp.4, 2012, https://doi.org/10.3746/pnf.2012.17.4.293
  2. Dietary Effects of Post-fermented Green Tea by Monascus pilosus on the Body Weight, Serum Lipid Profiles and the Activities of Hepatic Antioxidative Enzymes in Mouse Fed a High Fat Diet vol.55, pp.2, 2012, https://doi.org/10.3839/jabc.2011.064
  3. Effects of Hot-Water Extract of Mulberry Leaf Tea Fermented by Monascus pilosus on Body Weight and Hepatic Antioxidant Enzyme Activities in Mouse Fed a Normal Diet vol.14, pp.11, 2013, https://doi.org/10.5762/KAIS.2013.14.11.5646
  4. Effects of Mulberry Leaf Tea Fermented by Monascus pilosus on Body Weight and Hepatic Antioxidant Enzyme Activities in Mouse Fed High-Fat Diet vol.26, pp.1, 2013, https://doi.org/10.9799/ksfan.2013.26.1.066
  5. Dietary Effects of Fermented Soybean Curd Residue (Biji) on Body Weight, Serum Lipid Profiles, and Antioxidation-Related Enzymes Activity of Mice Fed a High Fat Diet vol.42, pp.7, 2013, https://doi.org/10.3746/jkfn.2013.42.7.1043
  6. on body weight, serum lipid profiles and activities of hepatic antioxidative enzymes in mice fed high fat diets vol.46, pp.1, 2013, https://doi.org/10.4163/kjn.2013.46.1.5
  7. Effect of Soybean Curd Residue Fermented by Monascus pilosus on the High fat Diet-Induced Obese Mice vol.57, pp.1, 2014, https://doi.org/10.3839/jabc.2014.002
  8. Isolation and Identification of Triterpenoids and Sterols from the Flowers of Chionanthus retusus Lindl. & Paxton vol.58, pp.3, 2015, https://doi.org/10.3839/jabc.2015.037
  9. , inhibits adipogenesis through modulation of FoxO1 pathway in 3T3-L1 adipocytes vol.69, pp.3, 2017, https://doi.org/10.1111/jphp.12684
  10. Quality Characteristics and Antioxidant Activity of Mulberry Leaf Tea Fermented by Monascus pilosus vol.41, pp.5, 2012, https://doi.org/10.3746/jkfn.2012.41.5.706
  11. on the anti-obesity and lipids improvement vol.46, pp.6, 2013, https://doi.org/10.4163/jnh.2013.46.6.493
  12. Fucosterol from an Edible Brown Alga Ecklonia stolonifera Prevents Soluble Amyloid Beta-Induced Cognitive Dysfunction in Aging Rats vol.16, pp.10, 2018, https://doi.org/10.3390/md16100368
  13. Effects of waterborne copper on oxidative stress and immune responses in red seabream, Pagrus major vol.14, pp.3, 2018, https://doi.org/10.1007/s13273-018-0032-2
  14. Anti-adipogenic activity of the edible brown alga Ecklonia stolonifera and its constituent fucosterol in 3T3-L1 adipocytes vol.37, pp.6, 2011, https://doi.org/10.1007/s12272-013-0237-9
  15. Analysis of the main active ingredients and bioactivities of essential oil from Osmanthus fragrans Var. thunbergii using a complex network approach vol.11, pp.1, 2011, https://doi.org/10.1186/s12918-017-0523-0