BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
권호 표지
DOI QR코드

DOI QR Code

Anti-obesity and hypolipidemic effects of Rheum undulatum in high-fat diet-fed C57BL/6 mice through protein tyrosine phosphatase 1B inhibition

  • Lee, Woo-Jung (Natural Medicine Center, KIST Gangneung Institute) ;
  • Yoon, Goo (College of Pharmacy, Mokpo National University) ;
  • Hwang, Ye-Ran (Natural Medicine Center, KIST Gangneung Institute) ;
  • Kim, Yong-Kee (College of Pharmacy, Sookmyung Women's University) ;
  • Kim, Su-Nam (Natural Medicine Center, KIST Gangneung Institute)
  • 투고 : 2011.09.07
  • 심사 : 2011.10.24
  • 발행 : 2012.03.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Protein tyrosine phosphatase 1B (PTP1B) is important in the regulation of metabolic diseases and has emerged as a promising signaling target. Previously, we reported the PTP1B inhibitory activity of Rheum undulatum (RU). In the present study, we investigated the metabolic regulatory effects of RU in a high-fat diet (HFD) model. RU treatment significantly blocked body weight gain, which was accompanied by a reduction of feed efficiency. In addition, it led to a reduction of liver weight mediated by overexpression of PPAR${\alpha}$ and CPT1 in the liver, and an increase in the expression of adiponectin, aP2, and UCP3 in adipose tissue responsible for the reduction of total and LDL-cholesterol levels. Chrysophanol and physcion from RU significantly inhibited PTP1B activity and strongly enhanced insulin sensitivity. Altogether, our findings strongly suggest that 2 compounds are novel PTP1B inhibitors and might be considered as anti-obesity agents that are effective for suppressing body weight gain and improving lipid homeostasis.

키워드

참고문헌

  1. Zimmet, P., Alberti, K. G. and Shaw, J. (2001) Global and societal implications of the diabetes epidemic. Nature 414, 782-787. https://doi.org/10.1038/414782a
  2. Moller, D. E. (2001) New drug targets for type 2 diabetes and the metabolic syndrome. Nature 414, 821-827. https://doi.org/10.1038/414821a
  3. Koren, S. and Fantus, I. G. (2007) Inhibition of the protein tyrosine phosphatase PTP1B: potential therapy for obesity, insulin resistance and type-2 diabetes mellitus. Best Pract. Res. Clin. Endocrinol. Metab. 21, 621-640. https://doi.org/10.1016/j.beem.2007.08.004
  4. Hooft van Huijsduijnen, R., 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
  5. Elchebly, M., Payette, P., Michaliszyn, E., Cromlish, W., Collins, S., Loy, A. L., Normandin, D., Cheng, A., Himms- Hagen, J., Chan, C. C., Ramachandran, C., Gresser, M. J., Tremblay, M. L. and Kennedy, B. P. (1999) Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 283, 1544-1548. https://doi.org/10.1126/science.283.5407.1544
  6. Klaman, L. D., Boss, O., Peroni, O. D., Kim, J. K., Martino, J. L., Zabolotny, J. M., Moghal, N., Lubkin, M., Kim, Y. B., Sharpe, A. H., Stricker-Krongrad, A., Shulman, G. I., Neel, B. G. and Kahn, B. B. (2000) Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol. Cell. Biol. 20, 5479-5489. https://doi.org/10.1128/MCB.20.15.5479-5489.2000
  7. Zabolotny, J. M., Bence-Hanulec, K. K., Stricker-Krongrad, A., Haj, F., Wang, Y., Minokoshi, Y., Kim, Y. B., Elmquist, J. K., Tartaglia, L. A., Kahn, B. B. and Neel, B. G. (2002) PTP1B regulates leptin signal transduction in vivo. Dev. Cell 2, 489-495. https://doi.org/10.1016/S1534-5807(02)00148-X
  8. Zhang, Y. N., Zhang, W., Hong, D., Shi, L., Shen, Q., Li, J. Y., Li, J. and Hu, L. H. (2008) Oleanolic acid and its derivatives: new inhibitor of protein tyrosine phosphatase 1B with cellular activities. Bioorg. Med. Chem. 16, 8697-8705. https://doi.org/10.1016/j.bmc.2008.07.080
  9. Choi, S. Z., Lee, S. O., Jang, K. U., Chung, S. H., Park, S. H., Kang, H. C., Yang, E. Y., Cho, H. J. and Lee, K. R. (2005) Antidiabetic stilbene and anthraquinone derivatives from Rheum undulatum. Arch. Pharm. Res. 28, 1027-1030. https://doi.org/10.1007/BF02977396
  10. Kuo, Y. C., Meng, H. C. and Tsai, W. J. (2001) Regulation of cell proliferation, inflammatory cytokine production and calcium mobilization in primary human T lymphocytes by emodin from Polygonum hypoleucum Ohwi. Inflamm. Res. 50, 73-82. https://doi.org/10.1007/s000110050727
  11. Bae, K. H. (2001) The medicinal plants of Korea, pp. 90, Kyohaksa, Seoul, Korea.
  12. Lee, W., Kim, S. N. and Yoon, G. (2010) Screening and medicinal herbs for inhibitory activity against protein tyrosine phosphatase 1B. Korean J. Pharmacogn. 41, 227-231.
  13. White, M. F., Takayama, S. and Kahn, C. R. (1985) Differences in the sites of phosphorylation of the insulin receptor in vivo and in vitro. J. Biol. Chem. 260, 9470-9478.
  14. Paneitz, A. and Westendorf, J. (1999) Anthranoid contents of rhubarb (Rheum undulatum L.) and other Rheum species and their toxicological relevance. Eur. Food Res. Technol. 210, 97-101. https://doi.org/10.1007/s002170050542
  15. Jung, M., Lee, Y., Park, M., Kim, H., Kim, H., Lim, E., Tak, J., Sim, M., Lee, D., Park, N., Oh, W. K., Hur, K. Y., Kang, E. S. and Lee, H. C. (2007) Design, synthesis, and discovery of stilbene derivatives based on lithospermic acid B as potent protein tyrosine phosphatase 1B inhibitors. Bioorg. Med. Chem. Lett. 17, 4481-4486. https://doi.org/10.1016/j.bmcl.2007.06.016

피인용 문헌

  1. Physcion induces mitochondria-driven apoptosis in colorectal cancer cells via downregulating EMMPRIN vol.764, 2015, https://doi.org/10.1016/j.ejphar.2015.07.008
  2. Physcion 8- O -β-glucopyranoside induces apoptosis, suppresses invasion and inhibits epithelial to mesenchymal transition of hepatocellular carcinoma HepG2 cells vol.83, 2016, https://doi.org/10.1016/j.biopha.2016.06.045
  3. Colloidal Aggregation and thein VitroActivity of Traditional Chinese Medicines vol.10, pp.4, 2015, https://doi.org/10.1021/cb5009487
  4. Protein tyrosine phosphatase 1B (PTP1B): A key regulator and therapeutic target in liver diseases vol.337, 2015, https://doi.org/10.1016/j.tox.2015.08.006
  5. Desoxyrhapontigenin, a potent anti-inflammatory phytochemical, inhibits LPS-induced inflammatory responses via suppressing NF-κB and MAPK pathways in RAW 264.7 cells vol.18, pp.1, 2014, https://doi.org/10.1016/j.intimp.2013.11.022
  6. Influence of wine-processing on the pharmacokinetics of anthraquinone aglycones and glycosides from rhubarb in hyperlipidemic hamsters vol.6, pp.30, 2016, https://doi.org/10.1039/C5RA27273D
  7. Identification and evaluation of magnolol and chrysophanol as the principle protein tyrosine phosphatase-1B inhibitory compounds in a Kampo medicine, Masiningan vol.186, 2016, https://doi.org/10.1016/j.jep.2016.03.063
  8. Hypolipidemic and antioxidant effects of ethanol extract of Cassia fistula fruit in hyperlipidemic mice vol.54, pp.12, 2016, https://doi.org/10.1080/13880209.2016.1185445
  9. Desoxyrhapontigenin up-regulates Nrf2-mediated heme oxygenase-1 expression in macrophages and inflammatory lung injury vol.2, 2014, https://doi.org/10.1016/j.redox.2014.02.001
  10. A Network Pharmacology Approach to Understanding the Mechanisms of Action of Traditional Medicine: Bushenhuoxue Formula for Treatment of Chronic Kidney Disease vol.9, pp.3, 2014, https://doi.org/10.1371/journal.pone.0089123
  11. Involvement of protein tyrosine phosphatases in adipogenesis: New anti-obesity targets? vol.45, pp.12, 2012, https://doi.org/10.5483/BMBRep.2012.45.12.235
  12. Very low-carbohydrate, high-fat, weight reduction diet decreases hepatic gene response to glucose in obese rats vol.15, pp.1, 2018, https://doi.org/10.1186/s12986-018-0284-9