In vitro Anti-diabetic Effects of Crude Extracts of Platycodi Radix

In vitro에서 길경 추출 분획물의 항당뇨 효과 조사

  • 고병섭 (한의학 연구원 한약품질 검사팀) ;
  • 권대영 (한국식품연구원 기능성연구부) ;
  • 홍상미 (호서대학교 자연과학대학 식품영양학과) ;
  • 박선민 (기초과학연구소)
  • Published : 2007.12.01


Anti-diabetic effect of Platycodi radix (PR) extract fractions was determined if vitro by investigating insulin-like action, insulin sensitizing action, glucose-stimulated insulin secretion, gene expression related to ${\beta}-cell$ function and mass, and ${\alpha}$-glucoamylase suppressing action. Insulin-like activity was not promoted by the treatment of PR methanol factions in 373-L1 fibroblast. However, treatment with 0, 20 and 100% PR methanol fractions along with 1 ng/mL insulin increased insulin-stimulated glucose uptake in 373-L1 adipocytes. In addition, the treatment of 0% and 100% methanol fractions along with differentiation inducers significantly increased the differentiation of 373-L1 fibroblasts to adipocytes. These fractions may contain insulin sensitizer. The 20%, 80% and 100% methanol fractions enhanced glucose-stimulated insulin secretion in Min6 cells, insulin secreting cell line. This was related to the mechanism to promote glucose sensing and ${\beta}-cell$ proliferation, which was regulated by the induction of IRS-2, glucokinase and PDX-1 genes. As expected, 20, 80 and 100% methanol fractions increased mRNA levels of IRS-2, glucokinase and PDX-1 genes. However, PR fractions did not affect the ${\alpha}-glucoamylase$ activity in vitro. These data suggested that PR extract fractions have anti-diabetic actions through improving insulin sensitization, glucose-stimulated insulin secretion, and ${\beta}-cell$ proliferation. Therefore, PR extracts can be beneficial for anti-diabetic treatment in lean diabetic patients.


  1. DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM: A balanced overview. Diabetes Care 15: 318-353 (1992)
  2. Hennige AM, Burks DJ, Ozcan U, Kulkarni RN, Ye J, Park S, Schubert M, Fisher TL, Dow MA, Leshan R, White MF. Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetes. J. Clin. Invest. 112: 1521-1532 (2003)
  3. Weir GC, Bonner-Weir S. Five stages of evolving $\beta$-cell dysfunction during progression to diabetes. Diabetes 53: S16-S21 (2004)
  4. Park S, Dong X, Fisher TL, Dunn S, Omer AK, Weir G, White MF. Exendin-4 promotes IRS2 signaling to mediate pancreatic beta-cell growth and function. J. Biol. Chem. 281: 1159-1168 (2005)
  5. Lee KJ, You HJ, Park SJ, Kim YS, Chung YC, Jeong TC, Jeong HG. Hepatoprotective effects of Platycodon grandiflorum on acetaminophen- induced liver damage in mice. Cancer Lett. 174: 73-81 (2001)
  6. Choi CY, Kim JY, Kim YS, Chung YC, Seo JK, Jeong HG. Aqueous extract isolated from Platycodon grandiflorum elicits the release of nitric oxide and tumor necrosis factor-a from murine macrophages. Int. Immunopharm. 1: 1141-1151 (2001)
  7. Hong SJ, Fong JC, Hwang JH. Effect of crude drugs on glucose uptake in 3T3-L1 adipocyte. Gaxiong Yi Xue Ke Xue Za Zhi 16: 445-451 (2000)
  8. Jhala US, Canettieri G, Screaton RA, Kulkarni RN, Krajewski S, Reed J, Walker J, Lin X, White MF, Montminy M. cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2. Genes Dev. 17: 1575-1580 (2003)
  9. Wang X, Cahill CM, Pineyro MA, Zhou J, Doyle ME, Egan JM. Glucagon-like peptide-1 regulates the beta cell transcription factor, PDX-1, in insulinoma cells. Endocrinology 140: 4904-4907 (1999)
  10. Kurtz TW. New treatment strategies for patients with hypertension and insulin resistance. Am. J. Med. 119: S24-30 (2006)
  11. Kameda K, Chikaki M, Morimoto C, Jiang M, Okuda H. Insulin like action of trans-10-hydroxy-2-decanoic acid and its related substance. J. Traditional Med. 13: 456-457 (1996)
  12. Herrmann BL, Schatz H, Pfeiffer A. Continuous blood glucose monitoring: the acute effect of acarbose on blood glucose variations. Med. Klin. 93: 651-655 (1998)
  13. Ko BS, Kim HK, Park S. Insulin sensitizing and insulin-like effects of water extracts from Kalopanax pictus NAKA fractions in 3T3-L1 adipocytes. J. Korean Soc. Agr. Chem. Biotechnol. 45: 42-46 (2002)
  14. Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, Zhang Y, Bernal D, Pons S, Shulman GI, White MF. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391: 900-904 (1998)
  15. Movassat J, Beattie GM, Lopez AD, Hayek A. Exendin 4 up-regulates expression of PDX 1 and hastens differentiation and maturation of human fetal pancreatic cells. J. Clin. Endocr. Metab. 87: 4775-4781 (2002)
  16. Choi SB, Jun DW, Park S. The insulin sensitizing effect of homoisoflavone-enriched fraction in Liriope platyphylla Wang et Tang via $PI_3$-kinase pathway. Life Sci. 75: 2653-2664 (2004)
  17. Min HK. Clinical characteristics of Korean diabetic patients. Korean J. Diabetes 16: 163-170 (1992)
  18. Yamamoto H, Kurebayashi S, Hirose T, Kouhara H, Kasayama S. Reduced IRS-2 and GLUT4 expression in PPAR-gamma 2- induced adipocytes derived from C/EBP-beta and C/EBP-deltadeficient mouse embryonic fibroblasts. J. Cell Sci. 115: 3601-3607 (2002)
  19. Hayakawa T, Kondo T, Okumura N, Nagai K, Shibata T, Kitagawa M. Enteroglucagon release in disaccharide malabsorption induced by intestinal alpha-glucosidase inhibition. Am. J. Gastroenterol. 84: 523-526 (1989)
  20. Huo H, Guo X, Hong S, Jiang M, Liu X, Liao K. Lipid rafts/ caveolae are essential for insulin-like growth factor-1 receptor signaling during 3T3-L1 preadipocyte differentiation induction. J. Biol. Chem. 278: 11561-11569 (2003)
  21. Kim J, Choi S, Kong B, Oh Y, Shinn S. Insulin secretion and sensitivity during oral glucose tolerance test in Korean lean elderly women. J. Korean Med. Sci. 16: 592-597 (2001)
  22. Kim YP, Lee EB, Kim SY, Li D, Ban HS, Lim SS, Shin KH, Ohuchi K. Inhibition of prostaglandin E2 production by platycodin D isolated from the root of Platycodon grandiflorum. Planta Med. 67: 362-364 (2001)
  23. Choi BS, Park S. A steroidal glycoside from polygonatum odoratum (mill.) druce. improves insulin resistance but does not alter insulin secretion in 90% pancreatectomized rats. Biosci. Biotech. Bioch. 66: 2036-2043 (2002)
  24. Miki H, Yamauchi T, Suzuki R, Komeda K, Tsuchida A, Kubota N, Terauchi Y, Kamon J, Kaburagi Y, Matsui J, Akanuma Y, Nagai R, Kimura S, Tobe K, Kadowaki T. Essential role of insulin receptor substrate 1 (IRS-1) and IRS-2 in adipocyte differentiation. Mol. Cell. Biol. 21: 2521-2532 (2001)
  25. Kim HK, Choi JS, Yoo DS, Choi YH, Yon GH, Hong KS, Lee BH, Kim HJ, Kim EU, Roh SH, Jeong YC, Kim YS, Ryu SY. HPLC analysis of saponins in Platycodi Radix. Korean J. Pharmacogn. 38: 18-25 (2007)
  26. Kadowaki T, Hara K, Yamauchi T, Terauchi Y, Tobe K, Nagai R. Molecular mechanism of insulin resistance and obesity. Exp. Biol. Med. 228: 1111-1117 (2003)
  27. Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 46: 3-19 (2003)
  28. Gerhold DL, Liu F, Jiang G, Li Z, Xu J, Lu M, Sachs JR, Bagchi A, Fridman A, Holder DJ, Doebber TW, Berger J, Elbrecht A, Moller DE, Zhang BB. Gene expression profile of adipocyte differentiation and its regulation by peroxisome proliferation-activated receptor-gamma agonists. Endocrinology 143: 2106-2118 (2002)
  29. Choi SB, Ko BS, Park SK, Jang JS, Park S. Insulin sensitizing and $\alpha$-glycoamylase inhibitory action of sennosides, rheins, and rhaponticin in Rhei Rhizoma. Life Sci. 78: 934-942 (2006)
  30. Choi SB, Park S. The effects of water extract of Polygonatum Odoratum (Mill) Druce on insulin resistance in 90% pancreatec-tomized rats. J. Food Sci. 67: 2375-2379 (2002)
  31. Krenisky JM, Luo J, Carney JR. Isolation and antihyperglycemic activity of bakuchiol from Otholobium pubsecens (Fabaceae), a peruvian medicinal plant used for the treatment of diabetes. Biol. Pharm. Bull. 22: 1137-1140 (1999)