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Archives of Pharmacal Research

, Volume 33, Issue 1, pp 151–157 | Cite as

Effect of protopanaxadiol derivatives in high glucose-induced fibronectin expression in primary cultured rat mesangial cells: Role of mitogen-activated protein kinases and Akt

  • Min Jung Park
  • Chun Sik Bae
  • Seul Ki Lim
  • Dong Il Kim
  • Jae Cheong Lim
  • Jong Choon Kim
  • Ho Jae Han
  • Jae Hak Moon
  • Kye Yeop Kim
  • Kyung-Chul Yoon
  • Soo Hyun Park
Article

Abstract

A lot of anti-diabetic agents using natural plants have been extensively studied. Ginsenosides are known to be used as a remedy for diabetes in Asian countries and American Societies. Diabetic nephropathy is a major complication of diabetes mellitus. Extracellular matrix in mesangial cells is mainly composed of fibronectin and the increase of fibronectin is a hallmark of diabetic nephropathy. Protopenaxadiol (PPD) is a major component of total ginseng. Thus, we examined the regulatory mechanism of PPD derivatives-induced preventive effect of fibronectin expression in mesangial cells cultivated under diabetic condition. In present study, ginsenoside Rb1 prevented the high glucose-induced increase of fibronectin expression in mesangial cells. Ginsenoside Rb2 and Rg3 also mildly inhibited it. However, ginsenoside Rc and Rd did not prevent the high glucose-induced increase of fibronectin expression in mesangial cells. In addition, ginsenoside Rb1 prevented high glucose-induced phosphorylation of p44/42 mitogen activated protein kinase (MAPK), p38 MAPK, JNK/SAPK, and Akt. These results suggest that ginsenoside Rb1 is the most powerful component of PPD derivatives. In conclusion, ginsenoside Rb1 prevented high glucose-induced increase of fibronectin expression via the inhibition of MAPK-Akt signaling cascade.

Key words

Ginsenosides Diabetic nephropathy Fibronectin Akt Mitogen activated protein kinases 

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References

  1. Attele, A. S., Wu, J. A., and Yuan, C. S., Ginseng pharmacology: multiple constituents and multiple actions. Biochem. Pharmacol., 58, 1685–1693 (1999).CrossRefPubMedGoogle Scholar
  2. Awazu, M., Ishikura, K., Hida, M., and Hoshiya, M., Mechanisms of mitogen-activated protein kinase activation in experimental diabetes. J. Am. Soc. Nephrol., 10, 738–745 (1999).PubMedGoogle Scholar
  3. Bae, J. W. and Lee, M. H., Effect and putative mechanism of action of ginseng on the formation of glycated hemoglobin in vitro. J. Ethnopharmacol., 91, 137–140 (2004).CrossRefPubMedGoogle Scholar
  4. Bradford, M. M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 72, 248–254 (1976).CrossRefPubMedGoogle Scholar
  5. Buettner, C., Yeh, G. Y., Phillips, R. S., Mittleman, M. A., and Kaptchuk, T. J., Systematic review of the effects of ginseng on cardiovascular risk factors. Ann. Pharmacother., 40, 83–95 (2006).PubMedGoogle Scholar
  6. Catherwood, M. A., Powell, L. A., Anderson, P., McMaster, D., Sharpe, P. C., and Trimble, E. R., Glucose-induced oxidative stress in mesangial cells. Kidney Int., 61, 599–608 (2002).CrossRefPubMedGoogle Scholar
  7. Cho, W. C., Chung, W. S., Lee, S. K., Leung, A. W., Cheng, C. H., and Yue, K. K., Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats. Eur. J. Pharmacol., 550, 173–179 (2006).CrossRefPubMedGoogle Scholar
  8. Dey, L., Xie, J. T., Wang, A., Wu, J., Maleckar, S. A., and Yuan, C. S., Anti-hyperglycemic effects of ginseng: comparison between root and berry. Phytomedicine, 10, 600–605 (2003).CrossRefPubMedGoogle Scholar
  9. Jackle-Meyer, I., Szukics, B., Neubauer, K., Metze, V., Petzoldt, R., and Stolte, H., Extracellular matrix proteins as early markers in diabetic nephropathy. Eur. J. Clin. Chem. Clin. Biochem., 33, 211–219 (1995).PubMedGoogle Scholar
  10. Jeong, S. I., Kwak, D. H., Lee, S., Choo, Y. K., Woo, W. H., Keum, K. S., Choi, B. K., and Jung, K. Y., Inhibitory effects of Cnidium officinale Makino and Tabanus fulvus Meigan on the high glucose-induced proliferation of glomerular mesangial cells. Phytomedicine, 12, 648–655 (2005).CrossRefPubMedGoogle Scholar
  11. Kato, M., Yuan, H., Xu, Z. G., Lanting, L., Li, S. L., Wang, M., Hu, M. C., Reddy, M. A., and Natarajan, R., Role of the Akt/FoxO3a pathway in TGF-beta1-mediated mesangial cell dysfunction: a novel mechanism related to diabetic kidney disease. J. Am. Soc. Nephrol., 17, 3325–3335 (2006).CrossRefPubMedGoogle Scholar
  12. Kiefer, D. and Pantuso, T., Panax ginseng. Am. Fam. Physician, 68, 1539–1542 (2003).PubMedGoogle Scholar
  13. Kim, D. I., Lim, S. K., Park, M. J., Han, H. J., Kim, G. Y., and Park, S. H., The involvement of phosphatidylinositol 3- kinase/Akt signaling in high glucose-induced downregulation of GLUT-1 expression in ARPE cells. Life Sci., 80, 626–632 (2007).CrossRefPubMedGoogle Scholar
  14. Kobayashi, T., Matsumoto, T., and Kamata, K., The PI3-K/Akt pathway: roles related to alterations in vasomotor responses in diabetic models. J. Smooth Muscle Res., 41, 283–302 (2005).CrossRefPubMedGoogle Scholar
  15. Lee, G. T., Ha, H., Jung, M., Li, H., Hong, S. W., Cha, B. S., Lee, H. C., and Cho, Y. D., Delayed treatment with lithospermate B attenuates experimental diabetic renal injury. J. Am. Soc. Nephrol., 14, 709–720 (2003).CrossRefPubMedGoogle Scholar
  16. Li, Y. G., Chen, M., Chou, G. X., Wang, Z. T., and Hu, Z. B., Ruggedness/robustness evaluation and system suitability test on United States Pharmacopoeia XXVI assay ginsenosides in Asian and American ginseng by high-performance liquid chromatography. J. Pharm. Biomed. Anal., 35, 1083–1091 (2004).CrossRefPubMedGoogle Scholar
  17. Lin, C. L., Wang, F. S., Kuo, Y. R., Huang, Y. T., Huang, H. C., Sun, Y. C., and Kuo, Y. H., Ras modulation of superoxide activates ERK-dependent fibronectin expression in diabetes-induced renal injuries. Kidney Int., 69, 1593–1600 (2006).CrossRefPubMedGoogle Scholar
  18. Locatelli, F., Canaud, B., Eckardt, K. U., Stenvinkel, P., Wanner, C., and Zoccali, C., The importance of diabetic nephropathy in current nephrological practice. Nephrol. Dial. Transplant., 18, 1716–1725 (2003).CrossRefPubMedGoogle Scholar
  19. Mason, R. M. and Wahab, N. A., Extracellular matrix metabolism in diabetic nephropathy. J. Am. Soc. Nephrol., 14, 1358–1373 (2003).CrossRefPubMedGoogle Scholar
  20. Park, S. H., Lee, Y. J., Lim, M. J., Kim, E. J., Lee, J. H., and Han, H. J., High glucose inhibits fructose uptake in renal proximal tubule cells: involvement of cAMP, PLC/PKC, p44/42 MAPK, and cPLA2. J. Cell Physiol., 200, 407–416 (2004).CrossRefPubMedGoogle Scholar
  21. Purves, T., Middlemas, A., Agthong, S., Jude, E. B., Boulton, A. J., Fernyhough, P., and Tomlinson, D. R., A role for mitogen-activated protein kinases in the etiology of diabetic neuropathy. FASEB J., 15, 2508–2514 (2001).CrossRefPubMedGoogle Scholar
  22. Sen, P., Mukherjee, S., Ray, D., and Raha, S., Involvement of the Akt/PKB signaling pathway with disease processes. Mol. Cell. Biochem., 253, 241–246 (2003).CrossRefPubMedGoogle Scholar
  23. Tian, W., Zhang, Z., and Cohen, D. M., MAPK signaling and the kidney. Am. J. Physiol. Renal Physiol., 279, F593–F604 (2000).PubMedGoogle Scholar
  24. Vuksan, V. and Sievenpiper J. L., Herbal remedies in the management of diabetes: lessons learned from the study of ginseng. Nutr. Metab. Cardiovasc. Dis., 15, 149–160 (2005)CrossRefPubMedGoogle Scholar
  25. Wang, J., Huang, H., Liu, P., Tang, F., Qin, J., Huang, W., Chen, F., Guo, F., Liu, W., and Yang, B., Inhibition of phosphorylation of p38 MAPK involved in the protection of nephropathy by emodin in diabetic rats. Eur. J. Pharmacol., 553, 297–303 (2006).CrossRefPubMedGoogle Scholar
  26. Xie, J. T., Mchendale, S., and Yuan, C. S., Ginseng and diabetes. Am. J. Chin. Med., 33, 397–404 (2005a).CrossRefPubMedGoogle Scholar
  27. Xie, J. T., Mehendale, S. R., Wang, A., Han, A. H., Wu, J. A., Osinski, J., and Yuan, C. S., American ginseng leaf: ginsenoside analysis and hypoglycemic activity. Pharmacol. Res., 49, 113–117 (2004).CrossRefPubMedGoogle Scholar
  28. Xie, J. T., Wang, C. Z., Wang, A. B., Wu, J., Basila, D., and Yuan, C. S., Antihyperglycemic effects of total ginsenosides from leaves and stem of Panax ginseng. Acta Pharmacol. Sin., 26, 1104–1110 (2005b).CrossRefPubMedGoogle Scholar
  29. Xie, X. S., Liu, H. C., Yang, M., Zuo, C., Deng, Y., and Fan, J. M., Ginsenoside Rb1, a panoxadiol saponin against oxidative damage and renal interstitial fibrosis in rats with unilateral ureteral obstruction. Chin. J. Integr. Med., 15, 133–40 (2009).CrossRefPubMedGoogle Scholar
  30. Yip, T. T., Lau, C. N., Kong, Y. C., Yung, K. H., Kim, J. H., and Woo, W. S. Ginsenoside compositions of Panax ginseng C.A. Meyer tissue culture and juice. Am. J. Chin. Med., 13, 89–92 (1985).CrossRefPubMedGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea and Springer Netherlands 2010

Authors and Affiliations

  • Min Jung Park
    • 1
  • Chun Sik Bae
    • 1
  • Seul Ki Lim
    • 1
  • Dong Il Kim
    • 1
  • Jae Cheong Lim
    • 1
  • Jong Choon Kim
    • 1
  • Ho Jae Han
    • 1
  • Jae Hak Moon
    • 2
  • Kye Yeop Kim
    • 3
  • Kyung-Chul Yoon
    • 4
  • Soo Hyun Park
    • 1
  1. 1.Bio-therapy Human Resources Center, College of Veterinary MedicineChonnam National UniversityGwangjuKorea
  2. 2.Department of Food Science & Technology, and Functional Food Research CenterChonnam National UniversityGwangjuKorea
  3. 3.College of Health and WelfareDongshin UniversityNajuKorea
  4. 4.Department of OphthalmologyChonnam National University Medical School and HospitalGwangjuKorea

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