Cholesterol-lowering effects and potential mechanisms of chitooligosaccharide capsules in hyperlipidemic rats

  • Yao Jiang
  • Chuhan Fu
  • Guihua Liu
  • Jiao Guo
  • Zhengquan Su
Keywords: Chitosan oligosaccharide, Antihyperlipidemic, Gene Difference Expression, High-fat diet, CYP7A1, HMGCR

Abstract

Background: Chitooligosaccharide (COS) has shown potential antihyperlipidemic activity in a few studies as
a functional food.

Method: We investigated the cholesterol-lowering effect and potential mechanisms of chitooligosaccharide
capsules (COSTC) in male SD rats fed a high-fat diet.

Results: COSTC could ameliorate serum lipid levels. Simultaneously, the cholesterol-lowering effect is probably
attributed to its role in two pathways: upregulating the gene expression and activity of cholesterol 7α-hydroxylase (CYP7A1), liver X receptor alpha (LXRA), and peroxisome proliferation activated receptor-α (PPARα), which facilitates the conversion of cholesterol into bile acid; downregulating the gene expression and activity of enzymes including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and sterol-responsive element binding protein-2 (SREBP2) and upregulating the low-density lipoprotein receptor (LDLR) to reduce the denovo synthesis of cholesterol.

Conclusion: Studies have suggested that COSTC has potential usefulness as a natural supplement or functional food for preventing and treating hyperlipidemia.

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References


  1. Schonfeld WPG, Rudel LL, Nelson C, Epstein M, Olson RE. Effects of dietary cholesterol and fatty acids on plasma lipoproteins. J Clin Invest 1982; 69: 1072–80.

  2. Ross R, Harker L. Hyperlipidemia and atherosclerosis. Science 1976; 193: 1094–100.

  3. Di Croce GBL, Trentalance A. Independent behavior of rat liver LDL receptor and HMGCoA Reductase under estrogen treatment. Biochem Bioph Res Co 1996; 224: 345–50.

  4. Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, et al. Ono, MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice. Nat Commun 2013; 4: 2883.

  5. Zhu Z, Lin Z, Jiang H, Jiang Y, Zhao M, Liu X. Hypolipidemic effect of Youcha in hyperlipidemia rats induced by high-fat diet. Food Funct 2017; 8: 1680–7.

  6. Dossi CG, Cadagan C, San Martin M, Espinosa A, Gonzalez-Manan A, Silva D, et al. Effects of rosa mosqueta oil supplementation in lipogenic markers associated with prevention of liver steatosis. Food Funct 2017; 8: 832–41.

  7. He K, Li X, Xiao Y, Yong Y, Zhang Z, Li S, et al. Hypolipidemic effects of Myrica rubra extracts and main compounds in C57BL/6j mice. Food Funct 2016; 7: 3505–15.

  8. Miceli N, Modello MR, Monforte MT, Sdrafkakis V, Dugo P, Crupi ML, et al. Hypolipidemic effects of citrus bergamia Risso et Poiteau Juice in rats fed a hypercholesterolemic diet. J Agric Food Chem 2007; 55: 10671–7.

  9. Campins L, Camps M, Riera A, Pleguezuelos E, Yebenes JC, Serra-Prat M. Oral drugs related with muscle wasting and sarcopenia. A review. Pharmacology 2017; 99: 1–8.

  10. Wiggers JK, van Golen RF, Verheij J, Dekker AM, van Gulik TM, Heger M. Atorvastatin does not protect against ischemia-reperfusion damage in cholestatic rat livers. BMC Surg 2017; 17: 35.

  11. Fu C, Jiang Y, Guo Y, Su Z. Natural products with anti-obesity effects and different mechanisms of action. J Agric Food Chem 2016; 64: 9571–85.

  12. Lai YS, Lee WC, Lin YE, Ho CT, Lu KH, Lin SH, et al. Ginger essential oil ameliorates hepatic injury and lipid accumulation in high fat diet-induced nonalcoholic fatty liver disease. J Agric Food Chem 2016; 64: 2062–71.

  13. Jiang C, Wang Q, Wei Y, Yao N, Wu Z, Ma Y. Cholesterol-lowering effects and potential mechanisms of different polar extracts from Cyclocarya paliurus leave in hyperlipidemic mice. J Ethnopharmacol 2015; 176: 17–26.

  14. Hamer SN, Cord-Landwehr S, Biarnes X, Planas A, Waegeman H, Moerschbacher BM, et al. Enzymatic production of defined chitosan oligomers with a specific pattern of acetylation using a combination of chitin oligosaccharide deacetylases. Sci Rep. 2015; 5: 8716.

  15. Huang J, Xie H, Hu S, Xie T, Gong J, Jiang C, et al. Preparation, characterization, and biochemical activities of N-(2-Carboxyethyl) chitosan from squid pens. J Agric Food Chem 2015; 63: 2464–71.

  16. Zou P, Yang X, Wang J, Li Y, Yu H, Zhang Y, et al. Advances in characterisation and biological activities of chitosan and chitosan oligosaccharides. Food Chem 2016; 190: 1174–81.

  17. Muanprasat C, Chatsudthipong V. Chitosan oligosaccharide: biological activities and potential therapeutic applications. Pharmacol Ther 2017; 170: 80–97.

  18. Ngo D.-H, Ngo T.-S, Kang D.-N, Je K.-H, Pham J.-Y, Byun HN.-D, et al. Biological effects of chitosan and its derivatives. Food Hydrocolloid 2015; 51: 200–16.

  19. Chatchai VC. Muanprasat chitosan oligosaccharide: biological activities and potential therapeutic applications. Pharmacol Therapeut 2017; 170: 80–97.

  20. Pan H, Yang Q, Huang G, Ding C, Cao P, Huang L, et al. Hypolipidemic effects of chitosan and its derivatives in hyperlipidemic rats induced by a high-fat diet. Food Nutr Res 2016; 60: 31137.

  21. Cao P, Huang G, Yang Q, Guo J, Su Z. The effect of chitooligosaccharides on oleic acid-induced lipid accumulation in HepG2 cells. Saudi pharm J: SPJ 2016; 24: 292–8.

  22. Cho EJ, Rahman A, Kim SW, Baek YM, Hwang HJ, Oh JY, et al. Chitosan oligosaccharides inhibit adipogenesis in 3T3-L1 adipocytes. J Microbiol Biotechnol 2008; 18: 80–7.

  23. Choi CR, Kim EK, Kim YS, Je JY, An SH, Lee JD, et al. Chitooligosaccharides decreases plasma lipid levels in healthy men. Int J Food Sci Nutr 2012; 63: 103–6.

  24. Wang D, Han J, Yu Y, Li X, Wang Y, Tian H, et al. Chitosan oligosaccharide decreases very-low-density lipoprotein triglyceride and increases high-density lipoprotein cholesterol in high-fat-diet-fed rats. Exp Biol Med (Maywood) 2011; 236: 1064–9.

  25. Tarazona S, Garcia-Alcalde F, Dopazo J, Ferrer A, Conesa A. Differential expression in RNA-seq: a matter of depth. Genome Res. 2011; 21: 2213–23.

  26. Zhengquan JG, Lanlan Huang SU. A method for preparation of COS capsule. Patent No.CN201510988017.7, 2015.12.24.

  27. Huang L, Chen J, Cao P, Pan H, Ding C, Xiao T, et al. Anti-obese effect of glucosamine and chitosan oligosaccharide in high-fat diet-induced obese rats. Mar Drugs. 2015; 13; 2732–56.

  28. Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism 2016; 65: 1038–48.

  29. Mota M, Banini BA, Cazanave SC, Sanyal AJ. Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease. Metabolism 2016; 65: 1049–61.

  30. Brown GT, Kleiner DE. Histopathology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Metabolism 2016; 65; 1080–6.

  31. Kiyoshiebihara A, Schneeman O. Interaction of bile acids, phospholipids, cholesterol and triglyceride with dietary fibers in the small intestine of rats. Carbohyd Fibers 1989; 119: 1100–6.

  32. Liu X, Xia W, Jiang Q, Xu Y, Yu P. Synthesis, characterization, and antimicrobial activity of kojic acid grafted chitosan oligosaccharide. J Agric Food Chem 2014; 62: 297–303.

  33. Qinna NA, Karwi QG, Al-Jbour N, Al-Remawi MA, Alhussainy TM, Al-So'ud KA, et al. Influence of molecular weight and degree of deacetylation of low molecular weight chitosan on the bioactivity of oral insulin preparations. Mar Drugs 2015; 13: 1710–25.

  34. Dong W, Han B, Shao K, Yang Z, Peng Y, Yang Y, et al. Effects of molecular weights on the absorption, distribution and urinary excretion of intraperitoneally administrated carboxymethyl chitosan in rats. J Mater Sci 2012; 23: 2945–52.

  35. Siow H.-L, Choi S.-B, Gan C.-Y. Structure–activity studies of protease activating, lipase inhibiting, bile acid binding and cholesterol-lowering effects of pre-screened cumin seed bioactive peptides. J Funct Foods 2016; 27: 600–11.

  36. He K, Hu Y, Ma H, Zou Z, Xiao Y, Yang Y, et al. Rhizoma coptidis alkaloids alleviate hyperlipidemia in B6 mice by modulating gut microbiota and bile acid pathways. Biochim Biophys Acta 2016; 1862: 1696–709.

  37. Kong B, Wang L, Chiang JY, Zhang Y, Klaassen CD, Guo GL. Mechanism of tissue-specific farnesoid X receptor in suppressing the expression of genes in bile-acid synthesis in mice. Hepatology 2012; 56: 1034–43.

  38. Zong C, Yu Y, Song G, Luo T, Li L, Wang X, Qin S. Chitosan oligosaccharides promote reverse cholesterol transport and expression of scavenger receptor BI and CYP7A1 in mice. Exp Biol Med (Maywood) 2012; 237: 194–200.

  39. Ducheix S, Lobaccaro JM, Martin PG, Guillou H. Liver X Receptor: an oxysterol sensor and a major player in the control of lipogenesis. Chem Phys Lipids 2011; 164: 500–14.

  40. Pawlak M, Lefebvre P, Staels B. Molecular mechanism of PPARalpha action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J Hepatol 2015; 62: 720–33.

Published
2018-06-14
How to Cite
1.
Jiang Y, Fu C, Liu G, Guo J, Su Z. Cholesterol-lowering effects and potential mechanisms of chitooligosaccharide capsules in hyperlipidemic rats. Food & Nutrition Research [Internet]. 14Jun.2018 [cited 20Sep.2018];62. Available from: https://foodandnutritionresearch.net/index.php/fnr/article/view/1446
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Original Articles