Hypoglycemic Effect of Paeonia lactiflora in High Fat Diet-Induced Type 2 Diabetic Mouse Model

고지방식이 유발 제2형 당뇨모델 마우스에서 작약의 혈당강하 효능

  • Yoon, In-Soo (College of Pharmacy and Natural Medicine Research Institute, Mokpo National University) ;
  • Jung, Yujung (Natural Medicine Center, KIST Gangneung Institute) ;
  • Kim, Hyun Jung (College of Pharmacy and Natural Medicine Research Institute, Mokpo National University) ;
  • Lim, Hyun Jin (College of Pharmacy and Natural Medicine Research Institute, Mokpo National University) ;
  • Cho, Seung-Sik (College of Pharmacy and Natural Medicine Research Institute, Mokpo National University) ;
  • Shim, Jung-Hyun (College of Pharmacy and Natural Medicine Research Institute, Mokpo National University) ;
  • Kang, Bok Yun (College of Pharmacy and Research Institute of Drug Development, Chonnam National University) ;
  • Cheon, Seung Hoon (College of Pharmacy and Research Institute of Drug Development, Chonnam National University) ;
  • Kim, Su-Nam (Natural Medicine Center, KIST Gangneung Institute) ;
  • Yoon, Goo (College of Pharmacy and Natural Medicine Research Institute, Mokpo National University)
  • 윤인수 (목포대학교 약학대학) ;
  • 정유정 (한국과학기술연구원 천연의약센터) ;
  • 김현정 (목포대학교 약학대학) ;
  • 임현진 (목포대학교 약학대학) ;
  • 조승식 (목포대학교 약학대학) ;
  • 심정현 (목포대학교 약학대학) ;
  • 강복윤 (전남대학교 약학대학) ;
  • 천승훈 (전남대학교 약학대학) ;
  • 김수남 (한국과학기술연구원 천연의약센터) ;
  • 윤구 (목포대학교 약학대학)
  • Received : 2014.06.17
  • Accepted : 2014.09.04
  • Published : 2014.09.30

Abstract

The roots of Paeonia lactiflora (PL) has been traditionally used as analgesic, spasmolytic and tonic in Korea, China, and Japan. As part of a search for herbal medicine to treat diabetes and obesity, we confirmed hypoglycemic effect of PL through high fat diet-induced obese and diabetic mice experiments in vivo. Treatment of ethanolic extract from PL led to a significant decrease in glucose level, which is comparable to that of an antidiabetic drug metformin. In addition, PL selectively stimulates the transcriptional activities of both peroxisome proliferator-activated receptor $(PPAR){\alpha}$ and ${\gamma}$, and inhibits enzymatic activity of protein tyrosine phosphatase 1B (PTP1B), which are predicted to be therapeutic target in treatment of type2 diabetes and obesity. Especially, the n-hexane fraction (Hx) from PL ethanol extract showed more potent activities on $PPAR{\alpha}$ and than others and exihibited moderate inhibitory activity against PTP1B.

Keywords

References

  1. 통계청 (2013) 2012년 사망 및 사망통계결과.
  2. Paton, C. M. and Ntambi, J. M. (2009) Biochemical and physiological function of stearoyl-CoA desaturase. Endocrino Metab. 297: E28-E37.
  3. Bajaj, M., Suraamornkul, S., Hardies, L. J., Glass, L., Musi, N. and DeFronzo, R. A. (2007) Effects of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus, Diabetologia 50: 1723-1731. https://doi.org/10.1007/s00125-007-0698-9
  4. Nissen, S. E. and Wolski, K. (2007) Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N. Engl. J. Med. 356: 2457-2471. https://doi.org/10.1056/NEJMoa072761
  5. Adeghate, E., Adem, A., Hasan, M. Y., Tekes, K. and Kalasz, H. (2011) Medicinal chemistry and actions of dual and pan PPAR modulators. Open Med. Chem. J. 5: 93-98. https://doi.org/10.2174/1874104501105010093
  6. Zhang, S. and Zhang, Z. Y. (2007) PTP1B as a drug target: recent developments in PTP1B inhibitor discovery. Drug Discov. Today 12: 373-381. https://doi.org/10.1016/j.drudis.2007.03.011
  7. Montalibet, J. and Kennedy, B. P. (2005) Therapeutic strategies for targeting PTP1B in diabetes. Drug Discov. Today Ther. Strateg. 2: 129-135. https://doi.org/10.1016/j.ddstr.2005.05.002
  8. Van Huijsduijnen, R. H., Bombrun, A. and Swinnen, D. (2002) Selecting protein tyrosine phosphatase as drug targets. Drug Discov. Today 7: 1013-1019. https://doi.org/10.1016/S1359-6446(02)02438-8
  9. 박종희 (2002) 한약백과도감 (하), 693. 도서출판 신일상사, 서울.
  10. 생약학교재 편찬위원회 (2006) 생약학, 200. 동명사, 서울.
  11. Lee W, Ham J, Kwon H. C., Kim Y. K. and Kim S. N. (2013) Anti-diabetic effect of amorphastilbol through $PPAR{\alpha}/{\gamma}$ dual activation in db/db mice. Biochem Biophys Res Commun. 432: 73-79. https://doi.org/10.1016/j.bbrc.2013.01.083
  12. Baumgartner, R. R., Steinmann, D., Heiss, E. H., Atanasov, A. G., Ganzera, M., Stuppner, H. and Dirsch, V. M. (2010) Bioactivity-guided isolation of 1,2,3,4,6-penta-O-galloyl-D-glucopyranose from Paeonia lactiflora roots as a PTP1B inhibitor. J. Nat. Prod. 73: 1578-1581. https://doi.org/10.1021/np100258e
  13. Kim, B., Lee, S. M., Hwang, T. Y. and Kim, H. S. (2013) Anti-oxidative and skin barrier effects of natural plants with a supercritical extract. Korean J. Food Preserv. 20: 597-601. https://doi.org/10.11002/kjfp.2013.20.5.597
  14. Hsu, F. L., Lai, C. W. and Cheng, J. T. (1997) Antihyperglycemic effects of paeoniflorin and 8-debenzoylpaeoniflorin, glucosides from the root of Paeonia lactiflora. Planta Med. 63: 323-325. https://doi.org/10.1055/s-2006-957692
  15. Lee, W., Kim, H. J., Moon, H. S., Kim, S. N. and Yoon, G. (2013) Screening of Korean traditional prescriptions with inhibitory activity against protein tyrosine phosphatase 1B and analysis of Jakgamhwangsinbu-tang (芍甘黃辛附湯) prescription. Kor. J. Pharmacogn. 44: 176-181.
  16. Zheng, L. Y., Pan, J. Q. and Lv, J. H. (2008) Effects of total glucosides of paeony on enhancing insulin sensitivity and antagonizing nonalcoholic fatty liver in rats. Zhongguo Zhong Yao Za Zhi. 33: 2385-2390.
  17. Desvergne, B. and Wahli, W. (1999) Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr. Rev. 20: 649-688.
  18. Lee, W., Yoon, G., Hwang, Y. R., Kim, Y. K. and Kim, S. N. (2012) Anti-obesity and hypolipidemic effects of Rheum undulatum in high-fat diet-fed C57BL/6 mice through protein tyrosine phosphatase 1B inhibition. BMB Rep. 45: 141-146. https://doi.org/10.5483/BMBRep.2012.45.3.141