Journal of Korean Medicine Rehabilitation (한방재활의학과학회지)

The society of Korean Medicine Rehabilitation (한방재활의학과학회)
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Anti-obesity Effect of Crataegus pinnatifida through Gut Microbiota Modulation in High-fat-diet Induced Obese Mice

산사의 장내 미생물 조절을 통한 항비만 효과

  • Kim, Min-Jee (Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Dongguk University) ;
  • Choi, Yura (Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Dongguk University) ;
  • Shin, Na Rae (Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Dongguk University) ;
  • Lee, Myeong-Jong (Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Dongguk University) ;
  • Kim, Hojun (Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Dongguk University)
  • 김민지 (동국대학교 한의과대학 한방재활의학과교실) ;
  • 최유라 (동국대학교 한의과대학 한방재활의학과교실) ;
  • 신나래 (동국대학교 한의과대학 한방재활의학과교실) ;
  • 이명종 (동국대학교 한의과대학 한방재활의학과교실) ;
  • 김호준 (동국대학교 한의과대학 한방재활의학과교실)
  • Received : 2019.09.15
  • Accepted : 2019.10.06
  • Published : 2019.10.31
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Abstract

Objectives This study was performed to evaluate anti-obesity effects of Crataegus pinnatifida (CP) on high-fat-diet induced obese mice. Methods The experimental animals were divided into four groups: normal diet (NOR) group, high fat diet (HFD) group, HFD+Xenical (XEN) group, and HFD+CP (CP) group. NOR group was fed a normal diet and the other three groups were fed high fat diet during the experiment. After the first two weeks of diet, XEN group and CP group were administered with XEN or CP for seven weeks, respectively. After that, we measured body weight, liver weight, fat weight, food intake, and serum concentrations of lipids and liver enzymes. Also the liver, intestine, fat tissue was removed to estimate the obesity-related mRNA expressions and the stool sample was collected to analyze the gut microbiota. Results We found that body weight, fat weight, and triglyceride level were decreased significantly in CP group compared to HFD group. Also CP significantly suppressed gene expressions associated with lipogenesis and inflammation, and increased gene expressions of browning of white adipose tissue and mitochondrial biogenesis. Moreover, it shifted the microbial diversity closer to that of NOR group and increased Firmicutes/Bacteriodetes ratio. Conclusions These results suggest that CP decrease body weight, fat weight and serum triglyceride. Also it inhibit inflammation and adipogenesis, altering gut microbial diversity and abundance. In conclusion, CP could be used as a therapeutic drug for obesity via gut microbiota modulation.

Keywords

References

  1. World Health Organization. Obesity and overweight. WHO Fact sheet. 2015. [cited 2019 Sep 13]; Available from: URL: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
  2. S eo MH, K im YH, H an K , Jung JH, P ark YG, L ee SS, Kwon HS, Lee WY, Yoo SJ. Prevalence of obesity and incidence of obesity-related comorbidities in Koreans based on National Health Insurance Service Health Checkup Data 2006-2015. J Obes Metab Syndr. 2018;27(1):46-52. https://doi.org/10.7570/jomes.2018.27.1.46
  3. Everett E, Tamimi H, Greer B, Swisher E, Paley P, Mandel L, Goff B. The effect of body mass index on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer. Gynecol Oncol. 2003;90(1):150-7. https://doi.org/10.1016/S0090-8258(03)00232-4
  4. von Gruenigen VE, Courneya KS, Gibbons HE, Kavanagh MB, Waggoner SE, Lerner E. Feasibility and effectiveness of a lifestyle intervention program in obese endometrial cancer patients: a randomized trial. Gynecol Oncol. 2008;109(1):19-26. https://doi.org/10.1016/j.ygyno.2007.12.026
  5. Seo MH, Lee WY, Kim SS, Kang JH, Kang JH, Kim KK, Kim BY, Kim YH, Kim WJ, Kim EM, Kim HS , Shin YA, Shin HJ, Lee KR, Lee KY, Lee SY, Lee SK, Lee JH, Lee CB, Chung S, Cho YH, Choi KM, Han JS , Yoo S J. 2018 Korean Society for the Study of Obesity Guideline for the Management of Obesity in Korea. J Obes Metab Syndr. 2019;28(1):40-5. https://doi.org/10.7570/jomes.2019.28.1.40
  6. Kim MK, Kim CS. Recent advances in anti-obesity agents. Korean J Med. 2018;93(6):501-8. https://doi.org/10.3904/kjm.2018.93.6.501
  7. Srivastava G, Apovian CM. Current pharmacotherapy for obesity. Nat Rev Endocrinol. 2018;14(1):12-24. https://doi.org/10.1038/nrendo.2017.122
  8. Korea Pharmaceutical Information Center. Information of herbal medicines [cited 2019 Sep 14]. Available from: URL: https://www.health.kr/researchInfo/herbalMedicine1_detail.asp?idx=537.
  9. Dehghani S, Mehri S, Hosseinzadeh H. The effects of Crataegus pinnatifida (Chinese hawthorn) on metabolic syndrome: A review. Iran J Basic Med Sci. 2019;22(5):460-8.
  10. Lee J, Cho E, Kwon H, Jeon J, Jung CJ, Moon M, Jeon M, Lee YC, Kim DH, Jung JW. The fruit of Crataegus pinnatifida ameliorates memory deficits in ${\beta}$-amyloid protein-induced Alzheimer's disease mouse model. J Ethnopharmacol. 2019;243:112107. https://doi.org/10.1016/j.jep.2019.112107
  11. Ryu SH, Chae JW. Effects of Crataegus Pinnatifida (CP) on allergic contact dermatitis (ACD) induced by DNCB in mice. Korean Journal of Pediatrics. 2014;28(3):59-73. https://doi.org/10.7778/jpkm.2014.28.3.059
  12. Shin IS, Lee MY, Lim HS, Ha H, Seo CS, Kim JC, Shin HK. An extract of crataegus pinnatifida fruit attenuates airway inflammation by modulation of matrix metalloproteinase-9 in ovalbumin induced asthma. PLoS One. 2012;7(9):e45734. https://doi.org/10.1371/journal.pone.0045734
  13. Wang T, Zhang P, Zhao C, Zhang Y, Liu H, Hu L, Gao X, Zhang D. Prevention effect in selenite-induced cataract in vivo and antioxidative effects in vitro of Crataegus pinnatifida leaves. Biol Trace Elem Res. 2011;142(1):106-16. https://doi.org/10.1007/s12011-010-8752-8
  14. Lee JJ, Lee HJ, Oh SW. Antiobesity effects of Sansa (Crataegi fructus) on 3T3-L1 cells and on high-fathigh-cholesterol diet-induced obese rats. J Med Food. 2017;20(1):19-29. https://doi.org/10.1089/jmf.2016.3791
  15. Khan MJ, Gerasimidis K, Edwards CA, Shaikh MG. Role of gut microbiota in the aetiology of obesity: proposed mechanisms and review of the literature. J Obes. 2016; 2016:7353642.
  16. Ansari A, Bose S, Yadav MK, Wang JH, Song YK, Ko SG, Kim H. CST, an herbal formula, exerts anti-obesity effects through brain-gut-adipose tissue axis modulation in high-fat diet fed mice. Molecules. 2016;21(11):E1522. https://doi.org/10.3390/molecules21111522
  17. Zhang S, Zhang C, Li M, Chen X, Ding K. Structural elucidation of a glucan from Crataegus pinnatifida and its bioactivity on intestinal bacteria strains. Int J Biol Macromol. 2019;128:435-43. https://doi.org/10.1016/j.ijbiomac.2019.01.158
  18. Clark JD, Gebhart GF, Gonder JC, Keeling ME, Kohn DF. The 1996 guide for the care and use of laboratory animals. ILAR Journal. 1997;38(1):41-48. https://doi.org/10.1093/ilar.38.1.41
  19. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI, Huttley GA, Kelley ST, Knights D, Koenig JE, Ley RE, Lozupone CA, McDonald D, Muegge BD, Pirrung M, Reeder J, Sevinsky JR, Turnbaugh PJ, Walters WA, Widmann J, Yatsunenko T, Zaneveld J, and Knight B. QIIME allows analysis of high-throughput community sequencing data. Nature Methods. 2010;7(5):335-336. https://doi.org/10.1038/nmeth.f.303
  20. Korean Society for the Study of Obesity. Causes of Obesity. [cited 2019 Sep 13]; Available from: URL: http://general.kosso.or.kr/html/?pmode=obesityCause.
  21. Aierken A, Buchholz T, Chen C, Zhang X, Melzig MF. Hypoglycemic effect of hawthorn in type II diabetes mellitus rat model. J Sci Food Agric. 2017;97(13):4557-61. https://doi.org/10.1002/jsfa.8323
  22. Kuo DH, Yeh CH, Shieh PC, Cheng KC, Chen FA, Cheng JT. Effect of Shan zha, a Chinese herbal product, on obesity and dyslipidemia in hamsters receiving high-fat diet. J Ethnopharmacol. 2009;124(3):544-50. https://doi.org/10.1016/j.jep.2009.05.005
  23. Won SH, Kwon KR, Rhim TJ, Kim DH. The effect of crataegi fructus pharmacopuncture on adipocyte metabolism. Journal of Korean Pharmacopuncture Institute. 2008;11(2):63-73. https://doi.org/10.3831/KPI.2008.11.2.063
  24. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science. 2005;308(5728):1635-8. https://doi.org/10.1126/science.1110591
  25. Castaner O, Goday A, Park YM, Lee SH, Magkos F, Shiow STE, Schroder H. The gut microbiome profile in obesity: a systematic review. Int J Endocrinol. 2018;2018:4095789. https://doi.org/10.1155/2018/4095789
  26. Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M, Arumugam M, Batto JM, Kennedy S, Leonard P, Li J, Burgdorf K, Grarup N, Jorgensen T, Brandslund I, Nielsen HB, Juncker AS, Bertalan M, Levenez F, Pons N, Rasmussen S, Sunagawa S, Tap J, Tims S, Zoetendal EG, Brunak S, Clement K, Dore J, Kleerebezem M, Kristiansen K, Renault P, Sicheritz-Ponten T, de Vos WM, Zucker JD, Raes J, Hansen T; MetaHIT consortium, Bork P, Wang J, Ehrlich SD, Pedersen O. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500(7464):541-6. https://doi.org/10.1038/nature12506
  27. Paek JK, Lee SY. Can gut microbiota modulation be used as a practical treatment for obesity? J Obes Metab Syndr. 2018;27(2):75-7. https://doi.org/10.7570/jomes.2018.27.2.75
  28. Yumuk V, Tsigos C, Fried M, Schindler K, Busetto L, Micic D, Toplak H. European guidelines for obesity management in adults. Obes Facts. 2015;8(6):402-24. https://doi.org/10.1159/000442721
  29. Korean Society of Lipid an Artherosclerosis. 2018 Korean Guidelines for the Management of Dyslipidemia 4th ed. 2018. [cited 2019 Sep 13]; Available from: URL: http://www.lipid.or.kr/bbs/?code=care.
  30. Korean Society of Lipid an Artherosclerosis. Dyslipidemia. [cited 2019 Sep 13]; Available from: URL: http://www.lipid.or.kr/faq/index2.php#none.
  31. Gholam PM, Flancbaum L, Machan JT, Charney DA, Kotler DP. Nonalcoholic fatty liver disease in severely obese subjects. Am J Gastroenterol. 2007;102(2):399-408. https://doi.org/10.1111/j.1572-0241.2006.01041.x
  32. Moseti D, Regassa A, Kim WK. Molecular regulation of adipogenesis and potential anti-adipogenic bioactive molecules. Int J Mol Sci. 2016;17(1):E124. https://doi.org/10.3390/ijms17010124
  33. Vargas-Castillo A, Fuentes-Romero R, Rodriguez-Lopez LA, Torres N, Tovar AR. Understanding the biology of thermogenic fat: is browning a new approach to the treatment of obesity? Arch Med Res. 2017;48(5):401-13. https://doi.org/10.1016/j.arcmed.2017.10.002
  34. Altshuler-Keylin S, Kajimura S. Mitochondrial homeostasis in adipose tissue remodeling. Sci Signal. 2017;10(468):eaai9248. https://doi.org/10.1126/scisignal.aai9248
  35. Chakraborti CK. New-found link between microbiota and obesity. World J Gastrointest Pathophysiol. 2015;6(4):110-9. https://doi.org/10.4291/wjgp.v6.i4.110
  36. Patterson E, Ryan PM, Cryan JF, Dinan TG, Ross RP, Fitzgerald GF, Stanton C. Gut microbiota, obesity and diabetes. Postgrad Med J. 2016;92(1087):286-300. https://doi.org/10.1136/postgradmedj-2015-133285

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