DOI QR코드

DOI QR Code

Effects of Compounds from Physalis angulata on Fatty Acid Synthesis and Glucose Metabolism in HepG2 Cells via the AMP-activated Protein Kinase Pathway

  • 투고 : 2020.06.28
  • 심사 : 2020.09.09
  • 발행 : 2020.09.30

초록

The ability of the total extract from Physalis angulata; three fractions after partitioning with n-hexane, ethyl acetate (TBE), and water; and four withanolides (compounds 1 - 4) to phosphorylate 5'-adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells was evaluated. The TBE fraction (50 ㎍/mL) activated p-ACC and p-AMPK expression most strongly. Compounds 1 - 4 (10 μM) upregulated p-ACC expression at different levels. Compound 4 induced the most significant changes in p-AMPK expression, followed by 1 and 2. Sterol regulatory element-binding proteins (SREBPs) play a functional role in the transcriptional regulation of the lipogenic pathway, including fatty acid synthase (FAS) and ACC. The effects of compounds 2 and 4 (10 μM) on FAS and SREBP-1c expression under high glucose conditions (30 mM) in HepG2 cells were evaluated further. Both dose-dependently inhibited FAS and SREBP-1c expression as well as lipid accumulation (1 - 10 μM) were compared to high-concentration glucose control, which upregulated FAS and SREBP-1c. These results suggest that compounds 2 and 4 upregulate AMPK, suppress FAS and SREBP-1c, and have potential effects on glucose and lipid metabolism.

키워드

참고문헌

  1. Browning, J. D.; Horton, J. D. J. Clin. Invest. 2004, 114, 147-152. https://doi.org/10.1172/JCI200422422
  2. Clark, J. M.; Brancati, F. L.; Diehl, A. M. Am. J. Gastroenterol. 2003, 98, 960-967. https://doi.org/10.1111/j.1572-0241.2003.07486.x
  3. Angulo, P. N. Engl. J. Med. 2002, 346, 1221-1231. https://doi.org/10.1056/NEJMra011775
  4. Nomura, H.; Kashiwagi, S.; Hayashi, J.; Kajiyama, W.; Tani, S.; Goto, M. Jpn. J. Med. 1988, 27, 142-149. https://doi.org/10.2169/internalmedicine1962.27.142
  5. Hilden, M.; Christoffersen, P.; Juhl, E.; Dalgaard, J. B. Scand. J. Gastroenterol. 1977, 12, 593-597. https://doi.org/10.3109/00365527709181339
  6. Bellentani, S.; Saccoccio, G.; Masutti, F.; Croce, L. S.; Brandi, G.; Sasso, F.; Cristanini, G.; Tiribelli, C. Ann. Intern. Med. 2000, 132, 112-119. https://doi.org/10.7326/0003-4819-132-2-200001180-00004
  7. Nakamuta, M.; Kohjima, M.; Morizono, S.; Kotoh, K.; Yoshimoto, T.; Miyagi, I.; Enjoji, M. Int. J. Mol. Med. 2005, 16, 631-635.
  8. Kohjima, M.; Enjoji, M.; Higuchi, N.; Kato, M.; Kotoh, K.; Yoshimoto, T.; Fujino, T.; Yada, M.; Yada, R.; Harada, N.; Takayanagi, R.; Nakamuta, M. Int. J. Mol. Med. 2007, 20, 351-358.
  9. Andersson, U.; Filipsson, K.; Abbott, C. R.; Woods, A.; Smith, K.; Bloom, S. R.; Carling, D.; Small, C. J. J. Biol. Chem. 2004, 279, 12005-12008. https://doi.org/10.1074/jbc.C300557200
  10. McGarry, J. D.; Mannaerts, G. P.; Foster, D. W. J. Clin. Invest. 1977, 60, 265-270. https://doi.org/10.1172/JCI108764
  11. Wang, X.; Sato, R.; Brown, M. S.; Hua, X.; Goldstein, J. L. Cell 1994, 77, 53-62. https://doi.org/10.1016/0092-8674(94)90234-8
  12. Yellaturu, C. R.; Deng, X.; Cagen, L. M.; Wilcox, H. G.; Mansbach, C. M.; Siddiqi, S. A.; Park, E. A.; Raghow, R.; Elam, M. B. J. Biol. Chem. 2009, 284, 7518-7532. https://doi.org/10.1074/jbc.M805746200
  13. Li, Y.; Xu, S.; Mihaylova, M. M.; Zheng, B.; Hou, X.; Jiang, B.; Park, O.; Luo, Z.; Lefai, E.; Shyy, J. Y. J.; Gao, B.; Wierzbicki, M.; Verbeuren, T. J.; Shaw, R. J.; Cohen, R. A.; Zang, M. Cell Metab. 2011, 13, 376-388. https://doi.org/10.1016/j.cmet.2011.03.009
  14. Kim, J. B.; Sarraf, P.; Wright, M.; Yao, K. M.; Mueller, E.; Solanes, G.; Lowell, B. B.; Spiegelman, B. M. J. Clin. Invest. 1998, 101, 1-9. https://doi.org/10.1172/JCI1411
  15. Magana, M. M.; Lin, S. S.; Dooley, K. A.; Osborne, T. F. J. Lipid Res. 1997, 38, 1630-1638. https://doi.org/10.1016/S0022-2275(20)37181-9
  16. Shimomura, I.; Shimano, H.; Korn, B. S.; Bashmakov, Y.; Horton, J. D. J. Biol. Chem. 1998, 273, 35299-35306. https://doi.org/10.1074/jbc.273.52.35299
  17. Kim, J. B.; Spiegelman, B. M. Genes Dev. 1996, 10, 1096-1107. https://doi.org/10.1101/gad.10.9.1096
  18. Klemm, D. J.; Leitner, J. W.; Watson, P.; Nesterova, A.; Reusch, J. E.; Goalstone, M. L.; Draznin, B. J. Biol. Chem. 2001, 276, 28430-28435. https://doi.org/10.1074/jbc.M103382200
  19. Zhou, G.; Myers, R.; Li, Y.; Chen, Y.; Shen, X.; Fenyk-Melody, J.; Wu, M.; Ventre, J.; Doebber, T.; Fujii, N.; Musi, N.; Hirshman, M. F.; Goodyear, L. J.; Moller, D. E. J. Clin. Invest. 2001, 108, 1167-1174. https://doi.org/10.1172/JCI13505
  20. Woods, A.; Azzout-Marniche, D.; Foretz, M.; Stein, S. C.; Lemarchand, P.; Ferre, P.; Foufelle, F.; Carling, D. Mol. Cell. Biol. 2000, 20, 6704-6711. https://doi.org/10.1128/MCB.20.18.6704-6711.2000
  21. dos Santos, J. A. A.; Tomassini, T. C. B; Xavier, D. C. D.; Ribeiro, I. M.; da Silva, M. T. G.; de Morais Filho, Z. B. Mem. Inst. Oswaldo Cruz 2003, 98, 425-428. https://doi.org/10.1590/S0074-02762003000300024
  22. Chiang, H. C.; Jaw, S. M.; Chen, C. F.; Kan, W. S. Anticancer Res. 1992, 12, 837-843.
  23. Lin, Y. S.; Chiang, H. C.; Kan, W. S.; Hone, E.; Shih, S. J.; Won, M. H. Am. J. Chin. Med. 1992, 20, 233-243. https://doi.org/10.1142/S0192415X92000242
  24. Soares, M. B. P.; Bellintani, M. C.; Ribeiro, I. M.; Tomassini, T. C. B.; dos Santos, R. R. Eur. J. Pharmacol. 2003, 459, 107-112. https://doi.org/10.1016/S0014-2999(02)02829-7
  25. Porika, R.; Poojari, S.; Lunavath, V.; Mamidala, E. J. Pharm. Biol. Sci. 2014, 9, 11-14.
  26. Damu, A. G.; Kuo, P. C.; Su, C. R.; Kuo, T. H.; Chen, T. H.; Bastow, K. F.; Lee, K. H.; Wu, T. S. J. Nat. Prod. 2007, 70, 1146-1152. https://doi.org/10.1021/np0701374
  27. He, Q. P.; Ma, L.; Luo, J. Y.; He, F. Y.; Lou, L. G.; Hu, L. H. Chem. Biodivers. 2007, 4, 443-449. https://doi.org/10.1002/cbdv.200790036
  28. Ismail, N.; Alam, M. Fitoterapia 2001, 72, 676-679. https://doi.org/10.1016/S0367-326X(01)00281-7
  29. Augustine, A. A.; Ufuoma, O. Planta Med. 2013, 79, PJ5. https://doi.org/10.1055/s-0033-1352209
  30. Nanumala, S. K.; Kannadhasan, R.; Gunda, K.; Sivakumar, G.; Somasekhar, P. Int. J. Pharm. Pharm. Sci. 2012, 4, 226-228.
  31. Hseu, Y. C.; Wu, C. R.; Chang, H. W.; Kumar, K. J. S.; Lin, M. K.; Chen, C. S.; Cho, H. J.; Huang, C. Y.; Huang, C. Y.; Lee, H. Z. J. Ethnopharmacol. 2011, 135, 762-771. https://doi.org/10.1016/j.jep.2011.04.016
  32. Hsieh, W. T.; Huang, K. Y.; Lin, H. Y.; Chung, J. G. Food Chem. Toxicol. 2006, 44, 974-983. https://doi.org/10.1016/j.fct.2005.11.013
  33. Murali, K. T.; Rajender, V.; Manoj, K. E. Int. J. Pharm. Bio. Sci. 2013, 4, 541-549.
  34. Abo, K. A.; Lawal, I. O. J. Adv. Sci. Res. 2013, 4, 32-36.
  35. Oladele, G. M.; Ode, O. J.; Akande, M. G.; Ogunbodede, M. A.; Simon, M. K. Int. J. A. PS. BMS. 2013, 2, 95-100.
  36. Sinha, S. C.; Ali, A.; Bagchi, A.; Sahai, M.; Ray, A. B. Planta Med. 1987, 53, 55-57. https://doi.org/10.1055/s-2006-962619
  37. Januario, A. H.; Filho, E. R.; Pietro, R. C. L. R.; Kashima, S.; Sato, D. N.; Franca, S. C. Phytother. Res. 2002, 16, 445-448. https://doi.org/10.1002/ptr.939
  38. Zang, M.; Zuccollo, A.; Hou, X.; Nagata, D.; Walsh, K.; Herscovitz, H.; Brecher, P.; Ruderman, N. B.; Cohen, R. A. J. Biol. Chem. 2004, 279, 47898-47905. https://doi.org/10.1074/jbc.M408149200
  39. Mosmann, T. J. Immunol. Methods 1983, 65, 55-63. https://doi.org/10.1016/0022-1759(83)90303-4