Inhibition of Adipocyte Differentiation by MeOH Extract from Carduus crispus through ERK and p38 MAPK Pathways

  • Lee, Eun-Jeong (Natural Products Research Institute, College of Pharmacy, Seoul National University) ;
  • Joo, Eun-Ji (Natural Products Research Institute, College of Pharmacy, Seoul National University) ;
  • Hong, Yoo-Na (Natural Products Research Institute, College of Pharmacy, Seoul National University) ;
  • Kim, Yeong-Shik (Natural Products Research Institute, College of Pharmacy, Seoul National University)
  • Received : 2011.10.06
  • Accepted : 2011.11.15
  • Published : 2011.12.30

Abstract

In this study, the effects of a methanol (MeOH) extract of Carduus crispus L. (Asteraceae) on adipogenesis was investigated in 3T3-L1 cells. To differentiate preadipocytes to adipocytes, confluent 3T3-L1 preadipocytes were treated with a hormone mixture, which included isobutylmethylxanthine, dexamethasone, and insulin (MDI). The methanol extract of C. crispus significantly decreased fat accumulation by inhibiting adipogenic signal transcriptional factors in MDI-induced 3T3-L1 cells in a dose-dependent manner. In MTT assays and on PI-staining, methanol extract of C. crispus inhibited the proliferation of 3T3-L1 cells during mitotic clonal expansion (MCE). The anti-adipogenic effect of the Carduus extract seemed to be associated with the upregulation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) pathways within the first 2 days after MDI treatment. These results suggest that methanol extract of C. crispus might be beneficial for the treatment of obesity.

Keywords

References

  1. Boney, C.M., Gruppuso, P.A., Faris, R.A., and Frackelton, A.R., The critical role of Shc in insulin-like growth factor-I-mediated mitogenesis and differentiation in 3T3-L1 preadipocytes. Mol. Endocrinol. 14, 805-813 (2000). https://doi.org/10.1210/me.14.6.805
  2. Bost, F., Aouadi, M., and Caron, L., The role of MAPKs in adipocyte differentiation and obesity. Biochimie 87, 51-56 (2005). https://doi.org/10.1016/j.biochi.2004.10.018
  3. Flier, J.S., Obesity wars: Molecular progress confronts an expanding epidemic. Cell. 116, 337-350 (2004). https://doi.org/10.1016/S0092-8674(03)01081-X
  4. Halberg, N., Wernstedt, A.I., and Scherer, P.E., The adipocyte as an endocrine cell. Endocrinol Metab Clin North Am. 37, 753-768 (2008). https://doi.org/10.1016/j.ecl.2008.07.002
  5. Harmon, A. and Harp, J., Differential effects of flavonoids on 3T3-L1 adipogenesis and lipolysis. Am J Physiol Cell Physiol. 280, C807-C813 (2001). https://doi.org/10.1152/ajpcell.2001.280.4.C807
  6. Hwang, J.T., Park, I.J., Shin, J.I., Lee, Y.K. and Lee, S.K., Genistein, EGCG and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochem Biophys Res Commun. 338, 694-699 (2005). https://doi.org/10.1016/j.bbrc.2005.09.195
  7. Jeong, da. M., Jung, H.A., and Choi, J.S., Comparative antioxidant activity and HPLC profiles of some selected Korean thistles. Arch Pharm Res. 31, 28-33 (2008). https://doi.org/10.1007/s12272-008-1116-7
  8. Kelly, D.E., Mckolanis, T.M., and Kelley, C.A., Comparative effects of rosiglitazone and metformin on fatty liver and visceral adiposity in type 2 diabetes millitus, Diabetes. 51, (Suppl. 2) 142 (2002).
  9. Kim, J.K., So, H., Youn, M.J., Kim, H.J., and Kim, Y., Hibiscus sabdariffa L. water extract inhibits the adipocyte differentiation through the PI3-K and MAPK pathway. J Ethnopharmacol. 114, 260-267 (2007). https://doi.org/10.1016/j.jep.2007.08.028
  10. Kim, S.H., Park, H.S., Lee, M.S, Cho, Y.J., and Kim, Y.S., Vitisin A inhibits adipocyte differentiation through cell cycle arrest in 3T3-L1 cells. Biochem Biophys Res Commun. 372, 108-113 (2008). https://doi.org/10.1016/j.bbrc.2008.04.188
  11. Lebovitz, H.E., Dole, J.F., and Patwardhan, R., Rosiglitazone monotheraphy is effective in patients with type 2 diabetes. J Clin Endocrinol Metab. 86, 280-288 (2001). https://doi.org/10.1210/jc.86.1.280
  12. MacDougald, O.A. and Lane, M.D., Transcriptional regulation of gene expression during adipocyte differentiation. Annu Rev Biochem. 64, 345-373 (1995). https://doi.org/10.1146/annurev.bi.64.070195.002021
  13. Miyazaki, Y., Matsuda, M., and Defronzo, R.A., Dose response effect of pioglitazone on insulin sensitivity and insulin secretion in type 2 diabetes. Diabetes care. 25, 517-523 (2002). https://doi.org/10.2337/diacare.25.3.517
  14. Pearsonn, G., Robinson, F., Gibson, T.B., Xu, M., and Cobb, M.H., Mitogen-activated protein (MAP) kinase pathway : Regulation and physiological functions. Endocr Rev. 22, 153-183 (2001). https://doi.org/10.1210/er.22.2.153
  15. Rosen, E.D. and Spiegelman, B.M., Molecular regulation of adipogenesis, Annu Rev Cell Dev Biol. 16, 145-171 (2000). https://doi.org/10.1146/annurev.cellbio.16.1.145
  16. Spalding, K.L., Arner, E., Westermark, P.O., Bernard, S., and Buchholz, B.A., Dynamics of fat cell turnover in humans. Nature, 453, 783-787 (2008). https://doi.org/10.1038/nature06902
  17. Srujana, R., Mary Anne, D.F., and Clifton, A.B., Phytochemicals and regulation of the adipocyte life cycle. J Nutr Biochem. 19, 717-726 (2007).
  18. Tang, Q.Q., Otto, T.C., and Land M.D., Mitotic clonal expansion: A synchronous process required for adipogenesis. Proc Natl Acad Sci. 100, 44-49 (2003). https://doi.org/10.1073/pnas.0137044100
  19. Wang, M., Wang, J.J., Li, J., Park, K., Qian, X., Ma, J.X., and Zhang, S.X., Pigment Epithelium-derived factor (PEDF) suppresses adipogenesis via inhibition of the MAPK/ERK pathway in 3T3-L1 preadipocytes. Am J Physiol Endocrinol Metab. 297, E1378-87 (2009). https://doi.org/10.1152/ajpendo.00252.2009
  20. Wang, T., Wang, Y., and Yamashita, H., Evodiamine inhibits adipogenesis via the EGFR-PKCalpha-ERK signaling pathway. FEBS Lett. 583, 3655-3659 (2009). https://doi.org/10.1016/j.febslet.2009.10.046
  21. Yang, J.Y., Della-Fera, M.A., Rayalam, S., Ambati, S., Hartzell, D.L., Park, H.J., and Baile, C.A., Enhanced inhibition of adipogenesis and induction of apoptosis in 3T3-L1 adipocytes with combinations of resveratrol and quercetin. Life Sci. 82, 1032-1039 (2008). https://doi.org/10.1016/j.lfs.2008.03.003
  22. Zhang, J.W., Tang, Q.Q., Vinson, C., and Lane, M.D., Dominant-negative c/EBP$\alpha$ disrupts mitotic clonal expansion and differentiation of 3T3- L1 preadipocytes. Proc Natl Acad Sci. 101, 43-47 (2004). https://doi.org/10.1073/pnas.0307229101
  23. Zhang, Q., Tu, G., Zhao, Y., and Cheng, T., Novel bioactive isoquinoline alkaloids from Carduus crispus. Tetrahedron. 58, 6795-6798 (2002). https://doi.org/10.1016/S0040-4020(02)00792-5