DOI QR코드

DOI QR Code

식이유도 비만 동물모델에서 마르멜로추출물의 항비만 효능 비교 연구

A Comparative Study on Anti-Obesity Efficacy of Cydonia oblonga Miller Fruit Extract in Diet-Induced Obesity Animal Models

  • 황정순 (주식회사 비엔지 연구개발연구소) ;
  • 황명오 (주식회사 비엔지 연구개발연구소) ;
  • 권기성 (차의과학대학교 식품생명공학과) ;
  • 김은지 (한림대학교 바이오헬스케어소재기업협업센터)
  • Jung Soon Hwang (Research Institute, BnG Inc.) ;
  • Myeong Oh Hwang (Research Institute, BnG Inc.) ;
  • Kisung Kwon (Department of Food Science and Biotechnology, Cha University) ;
  • Eun Ji Kim (Industry Coupled Cooperation Center for Bio Healthcare Materials, Hallym University)
  • 투고 : 2024.03.27
  • 심사 : 2024.05.23
  • 발행 : 2024.06.30

초록

Objectives: The objective of this study was to explore the anti-obesity effect of Cydonia oblonga Miller fruit extract (COME) and to compare its anti-obesity efficacy with Garcinia cambogia extract (GCE) in diet-induced obese mice. Methods: Five-week-old male C57BL/6 were allocated into four groups: control diet (CD), high-fat diet (HFD), HFD + 400 mg/kg body weight (BW)/day COME (H+C), or HFD + 400 mg/kg BW/day GCE (H+G) groups. COME or GCE was administered once a day by oral gavage for eight weeks. Body weight, body fat percentage, fat weight, and biochemical parameters in serum were measured. The expressions of transcription factors and their target genes in epididymal adipose tissues were analyzed by reverse transcription polymerase chain reaction. Results: COME reduced body weight, weight gain, body fat percentage, total white adipose tissue weight, adipocyte size, and serum levels of insulin and leptin in high-fat diet-induced obese C57BL/6 mice. COME suppressed the mRNA expressions of CCAAT/enhancer binding proteinα, peroxisome proliferator-activated receptorγ, sterol-regulatory element-binding protein-1c, fatty acid synthase, and adipocyte protein 2 and increased carnitine palmitoyl transferase 1 mRNA expression in epidydimal adipose tissues. The anti-obesity efficacy of COME was found to be similar to that of GCE at the same dose. However, COME more effectively decreased adipose tissue weights, epididymal adipocyte size, serum insulin and leptin compared to GCE. Conclusions: These results demonstrated that COME is not toxic and exhibits anti-obesity efficacy at a level similar to that of GCE, suggesting that COME may be applicable as an anti-obesity agent.

키워드

참고문헌

  1. Visscher TL, Seidell JC. The public health impact of obesity. Annu Rev Public Health. 2001 ; 22 : 355-75. https://doi.org/10.1146/annurev.publhealth.22.1.355
  2. Bray GA, Kim KK, Wilding JPH. World Obesity Federation. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev. 2017 ; 18(7) : 715-23. https://doi.org/10.1111/obr.12551
  3. Mahase E. Global cost of overweight and obesity will hit $4.32tn a year by 2035, report warns. BMJ. 2023 ; 380 : 523.
  4. Muller TD, Bluher M, Tschop MH, DiMarchi RD. Antiobesity drug discovery: advances and challenges. Nat Rev Drug Discov. 2022 ; 21(3) : 201-23. https://doi.org/10.1038/s41573-021-00337-8
  5. Chakhtoura M, Haber R, Ghezzawi M, Rhayem C, Tcheroyan R, Mantzoros CS. Pharmacotherapy of obesity: an update on the available medications and drugs under investigation. EClinicalMedicine. 2023 ; 58 : 101882.
  6. Shaik Mohamed Sayed UF, Moshawih S, Goh HP, Kifli N, Gupta G, Singh SK, et al. Natural products as novel anti-obesity agents: insights into mechanisms of action and potential for therapeutic management. Front Pharmacol. 2023 ; 14 : 1182937.
  7. Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. JAMA. 1998 ; 280(18) : 1596-600. https://doi.org/10.1001/jama.280.18.1596
  8. Hasegawa N. Garcinia extract inhibits lipid droplet accumulation without affecting adipose conversion in 3T3- L1 cells. Phytother Res. 2001 ; 15(2) : 172-3. https://doi.org/10.1002/ptr.689
  9. Kim KY, Lee HN, Kim YJ, Park T. Garcinia cambogia extract ameliorates visceral adiposity in C57BL/6J mice fed on a high-fat diet. Biosci Biotechnol Biochem. 2008 ; 72(7) : 1772-80. https://doi.org/10.1271/bbb.80072
  10. Haber SL, Awwad O, Phillips A, Park AE, Pham TM. Garcinia cambogia for weight loss. Am J Health Syst Pharm. 2018 ; 75(2) : 17-22. https://doi.org/10.2146/ajhp160915
  11. Mena-Garcia A, Bellaizac-Riascos AJ, Rada-Mendoza M, Chito-Trujillo DM, Ruiz-Matute AI, Sanz ML. Quality evaluation of dietary supplements for weight loss based on Garcinia cambogia. Nutrients. 2022 ; 14(15) : 3077.
  12. Abdollahi H. A review on history, domestication and germplasm collections of quince (Cydonia oblonga Mill.) in the world. Genet Resour Crop Evol. 2019 ; 66(5) : 1041-58. https://doi.org/10.1007/s10722-019-00769-7
  13. Ashraf MU, Muhammad G, Hussain MA, Bukhari SN. Cydonia oblonga M., a medicinal plant rich in phytonutrients for pharmaceuticals. Front Pharmacol. 2016 ; 7 : 163.
  14. Silva BM, Andrade PB, Ferreres F, Domingues AL, Seabra RM, Ferreira MA. Phenolic profile of quince fruit (Cydonia oblonga Miller) (pulp and peel). J Agric Food Chem. 2002 ; 50(16) : 4615-8. https://doi.org/10.1021/jf0203139
  15. Wojdylo A, Oszmianski J, Bielicki P. Polyphenolic composition, antioxidant activity, and polyphenol oxidase (PPO) activity of quince (Cydonia oblonga Miller) varieties. J Agric Food Chem. 2013 ; 61(11) : 2762-72. https://doi.org/10.1021/jf304969b
  16. Hamauzu Y, Yasui H, Inno T, Kume C, Omanyuda M. Phenolic profile, antioxidant property, and anti-influenza viral activity of Chinese quince (Pseudocydonia sinensis Schneid.), quince (Cydonia oblonga Mill.), and apple (Malus domestica Mill.) fruits. J Agric Food Chem. 2005 ; 53(4) : 928-34. https://doi.org/10.1021/jf0494635
  17. Essafi-Benkhadir K, Refai A, Riahi I, Fattouch S, Karoui H, Essafi M. Quince (Cydonia oblonga Miller) peel polyphenols modulate LPS-induced inflammation in human THP-1-derived macrophages through NF-κB, p38MAPK and Akt inhibition. Biochem Biophys Res Commun. 2012 ; 418(1) : 180-5. https://doi.org/10.1016/j.bbrc.2012.01.003
  18. Mirmohammadlu M, Hosseini SH, Kamalinejad M, Esmaeili Gavgani M, Noubarani M, Eskandari MR. Hypolipidemic, hepatoprotective and renoprotective effects of Cydonia oblonga Mill. fruit in streptozotocininduced diabetic rats. Iran J Pharm Res. 2015 ; 14(4) : 1207-14.
  19. Zhou W, Abdusalam E, Abliz P, Reyim N, Tian S, Aji Q, et al. Effect of Cydonia oblonga Mill. fruit and leaf extracts on blood pressure and blood rheology in renal hypertensive rats. J Ethnopharmacol. 2014 ; 152(3) : 464-9. https://doi.org/10.1016/j.jep.2014.01.018
  20. Umar A, Iskandar G, Aikemu A, Yiming W, Zhou W, Berke B, et al. Effects of Cydonia oblonga Miller leaf and fruit flavonoids on blood lipids and anti-oxydant potential in hyperlipidemia rats. J Ethnopharmacol. 2015 ; 169 : 239-43. https://doi.org/10.1016/j.jep.2015.04.038
  21. Lee HS, Jung JI, Hwang JS, Hwang MO, Kim EJ. Cydonia oblonga Miller fruit extract exerts an anti-obesity effect in 3T3-L1 adipocytes by activating the AMPK signaling pathway. Nutr Res Pract. 2023 ; 17(6) : 1043-55. https://doi.org/10.4162/nrp.2023.17.6.1043
  22. Lee HS, Jeon YE, Jung JI, Kim SM, Hong SH, Lee J, et al. Anti-obesity effect of Cydonia oblonga Miller extract in high-fat diet-induced obese C57BL/6 mice. J Funct Foods. 2022 ; 89 : 104945.
  23. 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. https://doi.org/10.1007/BF00280883
  24. Chen H, Sullivan G, Quon MJ. Assessing the predictive accuracy of QUICKI as a surrogate index for insulin sensitivity using a calibration model. Diabetes. 2005 ; 54(7) : 1914-25. https://doi.org/10.2337/diabetes.54.7.1914
  25. Lim SM, Lee HS, Jung JI, Kim SM, Kim NY, Seo TS, et al. Cyanidin-3-O-galactoside-enriched Aronia melanocarpa extract attenuates weight gain and adipogenic pathways in high-fat diet-induced obese C57BL/6 mice. Nutrients. 2019 ; 11(5) : 1190.
  26. Li J, Wu H, Liu Y, Yang L. High fat diet induced obesity model using four strains of mice: Kunming, C57BL/6, BALB/c and ICR. Exp Anim. 2020 ; 69(3) : 326-35. https://doi.org/10.1538/expanim.19-0148
  27. Lee HS, Lim SM, Jung JI, Kim SM, Lee JK, Kim YH, et al. Gynostemma pentaphyllum extract ameliorates high-fat diet-induced obesity in C57BL/6N mice by upregulating SIRT1. Nutrients. 2019 ; 11(10) : 2475.
  28. Aslan M, Orhan N, Orhan DD, Ergun F. Hypoglycemic activity and antioxidant potential of some medicinal plants traditionally used in Turkey for diabetes. J Ethnopharmacol. 2010 ; 128(2) : 384-9. https://doi.org/10.1016/j.jep.2010.01.040
  29. Diez JJ, Iglesias P. The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol. 2003 ; 148(3) : 293-300. https://doi.org/10.1530/eje.0.1480293
  30. Bauche IB, El Mkadem SA, Pottier AM, Senou M, Many MC, Rezsohazy R, et al. Overexpression of adiponectin targeted to adipose tissue in transgenic mice: impaired adipocyte differentiation. Endocrinology. 2007 ; 148(4) : 1539-49. https://doi.org/10.1210/en.2006-0838
  31. Brennan AM, Mantzoros CS. Drug insight: the role of leptin in human physiology and pathophysiology-emerging clinical applications. Nat Clin Pract Endocrinol Metab. 2006 ; 2(6) : 318-27. https://doi.org/10.1038/ncpendmet0196
  32. Obradovic M, Sudar-Milovanovic E, Soskic S, Essack M, Arya S, Stewart AJ, et al. Leptin and obesity: role and clinical implication. Front Endocrinol (Lausanne). 2021 ; 12 : 585887.
  33. Kim JB, Sarraf P, Wright M, Yao KM, Mueller E, Solanes G, et al. Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J Clin Invest. 1998 ; 101(1) : 1-9. https://doi.org/10.1172/JCI1411
  34. R osen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ, et al. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. Genes Dev. 2002 ; 16(1) : 22-6. https://doi.org/10.1101/gad.948702
  35. Tontonoz P, Spiegelman BM. Fat and beyond: the diverse biology of PPARgamma. Annu Rev Biochem. 2008 ; 77 : 289-312. https://doi.org/10.1146/annurev.biochem.77.061307.091829
  36. Latasa MJ, Griffin MJ, Moon YS, Kang C, Sul HS. Occupancy and function of the -150 sterol regulatory element and -65 E-box in nutritional regulation of the fatty acid synthase gene in living animals. Mol Cell Biol. 2003 ; 23(16) : 5896-907. https://doi.org/10.1128/MCB.23.16.5896-5907.2003
  37. Furuhashi M, Tuncman G, Gorgun CZ, Makowski L, Atsumi G, Vaillancourt E, et al. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature. 2007 ; 447(7147) : 959-65. https://doi.org/10.1038/nature05844
  38. Lundsgaard AM, Fritzen AM, Kiens B. Molecular regulation of fatty acid oxidation in skeletal muscle during aerobic exercise. Trends Endocrinol Metab. 2018 ; 29(1) : 18-30. https://doi.org/10.1016/j.tem.2017.10.011
  39. Kraemer FB, Shen WJ. Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis. J Lipid Res. 2002 ; 43(10) : 1585-94. https://doi.org/10.1194/jlr.R200009-JLR200