YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Oryung-san Ameliorates Pioglitazone Side Effects

오령산의 피오글리타존 부작용 경감 효과

  • Shin, Eun-Jung (Pharmacology and Clinical Pharmacy Lab., College of Pharmacy, Kyung Hee University) ;
  • Choi, Han-Byul (Pharmacology and Clinical Pharmacy Lab., College of Pharmacy, Kyung Hee University) ;
  • Han, Eun-Jung (Pharmacology and Clinical Pharmacy Lab., College of Pharmacy, Kyung Hee University) ;
  • Chung, Sung-Hyun (Pharmacology and Clinical Pharmacy Lab., College of Pharmacy, Kyung Hee University)
  • 신은정 (경희대학교 약학대학 약물학임상약학 교실) ;
  • 최한별 (경희대학교 약학대학 약물학임상약학 교실) ;
  • 한은정 (경희대학교 약학대학 약물학임상약학 교실) ;
  • 정성현 (경희대학교 약학대학 약물학임상약학 교실)
  • Published : 2007.10.31
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Abstract

Thiazolidinediones (TZDs) induce insulin sensitization through the activation of PPAR${\gamma}$. However, the undesirable effect such as weight gain was observed. The purpose of this study was to find out an herbal drug that could reduce the side effects of pioglitazone. Among herbal formula that we have searched, oryung-san (OR) inhibited the differentiation of preadipocytes and did not affect on glucose uptake in 3T3-L1 adipocytes. In vitro, glucose uptake assay and Oil Red-O staining in 3T3-L1 adipocytes were conducted. In vivo, pioglitazone (PIO, 30 mg/kg), oryung-san (OR, 300 mg/kg), or pioglitazone co-administered with oryung-san (PIO+OR) were administered orally for 7 weeks in high fat diet (HFD) fed ICR mice and measured the body weight and blood glucose level every week. PIO+OR group significantly reduced body weight gain, triglyceride, and total cholesterol compared to PIO group. In addition, PIO+OR group showed a significant reduction of plasma glucose level (72%) compared to HFD control group. Insulin levels in PIO+OR group was also markedly decreased by 85% and 41% compared to HFD control and PIO group, respectively. Diameter of white adipocytes was decreased in the PIO+OR group compared to that in PIO group. Moreover, PIO+OR group reduced expression of PPAR${\gamma}$ and SREBP1a compared to PIO group. Taken together, oryung-san can improve side effects of pioglitazone, such as weight gain and edema, and shows a synergistic effect in plasma insulin levels.

Keywords

References

  1. Alberti, K. G. and Zimmet, P. Z. : Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 13, 539 (1998)
  2. Bailey, C. J. : Insulin resistance and antidiabetic drugs. Biochem. Pharmaco. 58, 1511 (1999)
  3. Zhang, B. B. and Moller, D. E. : New approaches in the treatment of type 2 diabetes. Curr. Opin. Chem. Biol. 4, 461 (2000)
  4. Ribeiro, R. C., Kushner, P. J. and Baxter, J. D. : The nuclear hormone receptor gene superfamily. Annu. Rev. Med. 46, 443 (1995)
  5. Spiegelman, B. M., Kim, H. E. and Brun, J. B.: PPAR-gand the control of adipogenesis. Biochimie. 79, 111 (1997)
  6. Vidal-Puig, A. J., Considine, R. V., Jimenez-Linan, M., Werman, A., Pories, W. J. and Caro, J. E : Peroxisome proliferator-actovated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J. Clin. Invest. 99, 2416 (1997)
  7. Berger, J. P., Akiyama, T. E. and Meinke, P. T. : PPARs: therapeutic targets for metabolic disease. Trends Parmacol. Sci. 26, 244 (2005) https://doi.org/10.1016/j.tips.2005.03.003
  8. Staels, B. and Fruchart, J. C.: Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes. 54, 2460 (2005) https://doi.org/10.2337/diabetes.54.8.2460
  9. Chawia, A., Schwarz, E. J., Dimaculangan, D. D. and Lazar, M. A. : Peroxisome proliferator-activated receptor (PPAR) ${\gamma}$: adipose-predominant exression and induction early in adipocyte differentiation. Endocrinology 135, 798 (1994)
  10. Tontonoz, P., Hu, E. and Spiegelman, B. M. : Stimulation of adipogenesis in fibroblasts by PPAR ${\gamma}2$, a lipid-activated transcription factor Cell. 79, 1147 (1994)
  11. Sood, V, Colleran, K. and Burge, M. R. : Thiazolidinedions: a comparative review of approved uses. Diaetes. Technol. Ther. 2, 429 (2000)
  12. Lebovitz, H. E. : Dfferentiating members of th thiazoli-dinedione class: a focus on safety. Diabetes. Meta. Res. Rev. 18, 23 (2002)
  13. Oberfield, J. L., Collins, J. L., Holmes, C. P., Goreham, D. M., Cooper, J. P. and Cobb, J. E. : A peroxisome proliferator-activated receptor ligand inhibits adipocyte differentiation. Proc. Natl. Acad. Sci. 96, 6102 (1999)
  14. Rocchi, S., Picard, F., Vamecq, J., Gelman, L., Potier, N. and Zeyer, D. : A unique PPAR-${\gamma}$ ligand with potent insulin-sensitizing yet weak adipogenic activity. Mol. Cell. 8, 737 (2001)
  15. Misra, E, Chakrabarti, R., Vikramadithyan, R. K., Bolusu, G., Juluri, S. and Hiriyan, J. : PAT5A: a partial agonist of peroxisome proliferator-activated receptor g is a potent antidiabetic thiazolidinedione yet weakly adipogenic J. Pharmacol. Exp. Ther. 306, 763 (2003) https://doi.org/10.1124/jpet.103.049791
  16. Berger, J. P., Petro, A. E., Macnaul, K. L., Kelly, L. J., Zhang, B. B. and Richards, K.: Distinct properties and advantages of a novel peroxisome proliferator-activated protein [g] selective modulator. Mol. Endocrinol. 17, 662 (2003) https://doi.org/10.1210/me.2002-0217
  17. Huang, C., Zhang, Y., Gong, Z., Sheng, X., Li, Z., Zhang, W. and Zin, Y. : Berberine inhibits 3T3-L1 adipocyte differentiation through the PPAR-${\gamma}$ pathway. Biochem. Biophys. Res. Commun. 348, 571 (2006) https://doi.org/10.1016/j.bbrc.2006.07.095
  18. Chakrabrti, R., Misra, P., Vikramadithyan, R. K., Premkumar, M., Hiriyan, J., Datla, S. R., Damarla, R. K., suresh, J. and Rajagopalan, R. : Antidiabetic and hypolipidemic potential of DRF 2519-a dual activator of PPAR-${\alpha}$ and PPAR-${\gamma}$. Eur. J. Pharmacol. 491, 195 (2004) https://doi.org/10.1016/j.ejphar.2004.03.034
  19. Trinder, P. : Determination of blood glucose using an oxidase-peroxidase system with a non-carcinogenic chromogen. J. Clin. Pathol. 22, 158 (1969)
  20. Chomczynski, P. and Sacchi, N. : Single-step method of RNA isolation by acid guanidium thiocyanate-phenol chloroform extraction. Anal. Biochem. 162(1), 156 (1987)