Biomolecules & Therapeutics

  • 제28권5호
  • /
  • Pages.397-404
  • /
  • 2020
  • /
  • 1976-9148(pISSN)
  • /
  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
권호 표지
DOI QR코드

DOI QR Code

Diallyl Biphenyl-Type Neolignans Have a Pharmacophore of PPARα/γ Dual Modulators

  • Han, Yujia (College of Pharmacy and Natural Products Research Institute, Seoul National University) ;
  • Liu, Jingjing (College of Pharmacy and Natural Products Research Institute, Seoul National University) ;
  • Ahn, Sungjin (College of Pharmacy and Natural Products Research Institute, Seoul National University) ;
  • An, Seungchan (College of Pharmacy and Natural Products Research Institute, Seoul National University) ;
  • Ko, Hyejin (College of Pharmacy and Natural Products Research Institute, Seoul National University) ;
  • Shin, Jeayoung C. (College of Pharmacy and Natural Products Research Institute, Seoul National University) ;
  • Jin, Sun Hee (College of Pharmacy and Natural Products Research Institute, Seoul National University) ;
  • Ki, Min Won (College of Pharmacy and Natural Products Research Institute, Seoul National University) ;
  • Lee, So Hun (SK Bioland) ;
  • Lee, Kang Hyuk (SK Bioland) ;
  • Shin, Song Seok (SK Bioland) ;
  • Choi, Won Jun (College of Pharmacy, Dongguk University) ;
  • Noh, Minsoo (College of Pharmacy and Natural Products Research Institute, Seoul National University)
  • 투고 : 2019.10.29
  • 심사 : 2020.01.07
  • 발행 : 2020.09.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Adiponectin secretion-promoting compounds have therapeutic potentials in human metabolic diseases. Diallyl biphenyl-type neolignan compounds, magnolol, honokiol, and 4-O-methylhonokiol, from a Magnolia officinalis extract were screened as adiponectin-secretion promoting compounds in the adipogenic differentiation model of human bone marrow mesenchymal stem cells (hBM-MSCs). In a target identification study, magnolol, honokiol, and 4-O-methylhonokiol were elucidated as PPARα and PPARγ dual modulators. Diallyl biphenyl-type neolignans affected the transcription of lipid metabolism-associated genes in a different way compared to those of specific PPAR ligands. The diallyl biphenyl-type neolignan structure provides a novel pharmacophore of PPARα/γ dual modulators, which may have unique therapeutic potentials in diverse metabolic diseases.

키워드

참고문헌

  1. Ahn, S., Lee, M., An, S., Hyun, S., Hwang, J., Lee, J. and Noh, M. (2018) 2-Formyl-komarovicine promotes adiponectin production in human mesenchymal stem cells through $PPAR{\gamma}$ partial agonism. Bioorg. Med. Chem. 26, 1069-1075. https://doi.org/10.1016/j.bmc.2018.01.019
  2. Atanasov, A. G., Wang, J. N., Gu, S. P., Bu, J., Kramer, M. P., Baumgartner, L., Fakhrudin, N., Ladurner, A., Malainer, C., Vuorinen, A., Noha, S. M, Schwaiger, S., Rollinger, J. M., Schuster, D., Stuppner, H., Dirsch, V. M. and Heiss, E. H. (2013) Honokiol: a non-$adipogenicPPAR{\gamma}$ agonist from nature. Biochim. Biophys. Acta 1830, 4813-4819. https://doi.org/10.1016/j.bbagen.2013.06.021
  3. Bernardes, A., Souza, P. C., Muniz, J. R., Ricci, C. G., Ayers, S. D., Parekh, N. M., Godoy, A. S., Trivella, D. B., Reinach, P., Webb, P., Skaf, M. S. and Polikarpov, I. (2013) Molecular mechanism of peroxisome proliferator-activated receptor $\alpha$ activation by WY14643: a new mode of ligand recognition and receptor stabilization. J. Mol. Biol. 425, 2878-2893. https://doi.org/10.1016/j.jmb.2013.05.010
  4. Byun, Y., Park, J., Hong, S. H., Han, M. H., Park, S., Jung, H. and Noh, M. (2013) The opposite effect of isotype-selective monoamine oxidase inhibitors on adipogenesis in human bone marrow mesenchymal stem cells. Bioorg. Med. Chem. Lett. 23, 3273-3276. https://doi.org/10.1016/j.bmcl.2013.03.117
  5. Chakrabarti, P. (2010) Promoting adipose specificity: the adiponectin promoter. Endocrinology 151, 2408-2410. https://doi.org/10.1210/en.2010-0316
  6. Chen, Q., Shou. P., Zheng, C., Jiang, M., Cao, G., Yang, Q., Cao, J., Xie, N., Velletri, T., Zhang, X., Xu, C., Zhang, L., Yang, H., Hou, J., Wang, Y. and Shi, Y. (2016) Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? Cell Death Differ. 23, 1128-1139. https://doi.org/10.1038/cdd.2015.168
  7. Dalamaga, M., Diakopoulos, K. N. and Mantzoros, C. S. (2012) The role of adiponectin in cancer: a review of current evidence. Endocr. Rev. 33, 547-594. https://doi.org/10.1210/er.2011-1015
  8. Erickson, J. A., Jalaie, M., Robertson, D. H., Lewis, R. A. and Vieth, M. (2004) Lessons in molecular recognition: the effects of ligand and protein flexibility on molecular docking accuracy. J. Med. Chem. 47, 45-55. https://doi.org/10.1021/jm030209y
  9. Farmer, S. R. (2005) Regulation of PPARgamma activity during adipogenesis. Int. J. Obes. 29, S13-S16. https://doi.org/10.1038/sj.ijo.0802907
  10. Fukuen, S., Iwaki, M., Yasui, A., Makishima, M., Matsuda, M. and Shimomura, L. (2005) Sulfonylurea agents exhibit peroxisome proliferator-activated receptor gamma agonistic activity. J. Biol. Chem. 280, 23653-23659. https://doi.org/10.1074/jbc.M412113200
  11. Garcia-Vallve, S., Guasch, L., Tomas-Hernandez, S., del Bas, J. M., Ollendorff, V., Arola, L., Pujadas, G. and Mulero, M. (2015) Peroxisome proliferator-activated receptor $\gamma$ ($PPAR{\gamma}$) and ligand choreography: newcomers take the stage. J. Med. Chem. 58, 5381-5394. https://doi.org/10.1021/jm501155f
  12. Gross, B., Pawlak, M., Lefebvre, P. and Staels, B. (2017) PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD. Nat. Rev. Endocrinol. 13, 36-49. https://doi.org/10.1038/nrendo.2016.135
  13. Henry, R. R., Lincoff, A. M., Mudaliar, S., Rabbia, M., Chognot, C. and Herz, M. (2009) Effect of the dual peroxisome proliferator-activated $receptor-{\alpha}/{\gamma}$ agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study. Lancet 374, 126-135. https://doi.org/10.1016/S0140-6736(09)60870-9
  14. Home, P. (2011) Safety of PPAR agonists. Diabetes Care 34, S215-S219. https://doi.org/10.2337/dc11-s233
  15. Hughes, T. S., Giri, P. K., de Vera, I. M., Marciano, D. P., Kuruvilla, D. S., Shin, Y., Blayo, A. L., Kamenecka, T. M., Burris, T. P., Griffin, P. R. and Kojetin, D. J. (2014) An alternate binding site for $PPAR{\gamma}$ ligands. Nat. Commun. 5, 3571. https://doi.org/10.1038/ncomms4571
  16. Iwaki, M., Matsuda, M., Maeda, N., Funahashi, T., Matsuzawa, Y., Makishima, M. and Shimomura, I. (2003) Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes 52, 1655-1663. https://doi.org/10.2337/diabetes.52.7.1655
  17. Jain, M. R., Giri, S. R., Bhoi, B., Trivedi, C., Rath, A., Rathod, R., Ranvir, R., Kadam, S., Patel, H., Swain, P., Roy, S. S., Das, N., Karmakar, E., Wahli, W. and Patel, P. R. (2018) Dual $PPAR{\alpha}/{\gamma}$ agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models. Liver Int. 38, 1084-1094. https://doi.org/10.1111/liv.13634
  18. Kershaw, E. E. and Flier, J. S. (2004) Adipose tissue as an endocrine organ. J. Clin. Endocrinol. Metab. 89, 2548-2556. https://doi.org/10.1210/jc.2004-0395
  19. Kim, S. O., Han, Y., Ahn, S., An, S., Shin, J. C., Choi, H., Kim, H. J., Park, N. H., Kim, Y. J., Jin, S. H., Rho, H. S. and Noh, M. (2018) Kojylcinnamate esters are peroxisome proliferator-activated receptor ${\alpha}/{\gamma}$ dual agonists. Bioorg. Med. Chem. 26, 5654-5663. https://doi.org/10.1016/j.bmc.2018.10.010
  20. Lefterova, M. I., Haakonsson, A. K., Lazar, M. A. and Mandrup, S. (2014) $PPAR{\gamma}$ and the global map of adipogenesis and beyond. Trends Endocrinol. Metab. 25, 293-302. https://doi.org/10.1016/j.tem.2014.04.001
  21. Lehmann, J. M., Lenhard, J. M., Oliver, B. B., Ringold, G. M. and Kliewer, S. A. (1997) Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J. Biol. Chem. 272, 3406-3410. https://doi.org/10.1074/jbc.272.6.3406
  22. Liang, X., Xing, W., He, J., Fu, F., Zhang, W., Su, F., Liu, F., Ji, L., Gao, F., Su, H., Sun, X. and Zhang, H. (2015) Magnolol administration in normotensive young spontaneously hypertensive rats postpones the development of hypertension: role of increased PPAR gamma, reduced TRB3 and resultant alleviative vascular insulin resistance. PLoS ONE 10, e0120366. https://doi.org/10.1371/journal.pone.0120366
  23. Lincoff, A. M., Tardif, J. C., Schwartz, G. G., Nicholls, S. J., Ryden, L., Neal, B., Malmberg, K., Wedel, H., Buse, J. B., Henry, R. R., Weichert, A., Cannata, R., Svensson, A., Volz, D. and Grobbee, D. E. (2014) Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus: the AleCardio randomized clinical trial. JAMA 311, 1515-1525. https://doi.org/10.1001/jama.2014.3321
  24. Noh, M. (2012) Interleukin-17A increases leptin production in human bone marrow mesenchymal stem cells. Biochem. Pharmacol. 83, 661-670. https://doi.org/10.1016/j.bcp.2011.12.010
  25. Pfaffl, M. W., Horgan, G. W. and Dempfle, L. (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 30, e36. https://doi.org/10.1093/nar/30.9.e36
  26. Shin, D. W., Kim, S. N., Lee, S. M., Lee, W., Song, M. J., Park, S. M., Lee, T. R., Baik, J. H., Kim, H. K., Hong, J. H. and Noh, M. (2009) (-)-Catechin promotes adipocyte differentiation in human bone marrow mesenchymal stem cells through PPAR gamma transactivation. Biochem. Pharmacol. 77, 125-133. https://doi.org/10.1016/j.bcp.2008.09.033
  27. Straub, L. G. and Scherer, P. E. (2019) Metabolic messengers: adiponectin. Nat. Metab. 1, 334-339. https://doi.org/10.1038/s42255-019-0041-z
  28. Trott, O. and Olson, A. J. (2010) AutoDockVina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455-461.
  29. Wang, L., Waltenberger, B., Pferschy-Wenzig, E. M., Blunder, M., Liu, X., Malainer, C., Schuster, D., Blazevic, T., Schwaiger, S., Rollinger, J. M., Heiss, E. H., Schuster, D., Kopp, B., Bauer, R., Stuppner, H., Dirsch, V. M. and Atanasov, A. G. (2014) Natural product agonists of peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$): a review. Biochem. Pharmacol. 92, 73-89. https://doi.org/10.1016/j.bcp.2014.07.018
  30. Waragai, M., Ho, G., Takamatsu, Y., Shimizu, Y., Sugino, H., Sugama, S., Takenouchi, T., Masliah, E. and Hashimoto, M. (2018) Dual-therapy strategy for modification of adiponectin receptor signaling in aging-associated chronic diseases. Drug Discov. Today 23, 1305-1311. https://doi.org/10.1016/j.drudis.2018.05.009
  31. Xu, H. E., Lambert, M. H., Montana, V. G., Parks, D. J., Blanchard, S. G., Brown, P. J., Sternbach, D. D., Lehmann, J. M., Wisely, G. B., Willson, T. M., Kliewer, S. A. and Milburn, M. V. (1999) Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol. Cell 3, 397-403. https://doi.org/10.1016/S1097-2765(00)80467-0
  32. Xu, H. E., Stanley, T. B., Montana, V. G., Lambert, M. H., Shearer, B. G., Cobb, J. E., McKee, D. D., Galardi, C. M., Plunket, K. D., Nolte, R. T., Parks, D. J., Moore, J. T., Kliewer, S. A., Willson, T. M. and Stimmel, J. B. (2002) Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha. Nature 415, 813-817. https://doi.org/10.1038/415813a
  33. Yamauchi, T. and Kadowaki, T. (2008) Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases. Int. J. Obes. (Lond.) 32, S13-S18.
  34. Yamauchi, T., Kamonm, J., Minokoshi, Y. A., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., Eto, K., Akanuma, Y., Froguel, P., Foufelle, F., Ferre, P., Carling, D., Kimura, S., Nagai, R., Kahn, B. B. and Kadowaki, T. (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med. 8, 1288-1295. https://doi.org/10.1038/nm788
  35. Yu, J., Ahn, S., Kim, H. J., Lee, M., Ahn, S., Kim, J., Jin, S. H., Lee, E., Kim, G., Cheong, J. H., Jacobson, K. A., Jeong, L. S. and Noh, M. (2017) Polypharmacology of N6-(3-Iodobenzyl) adenosine-5′-N-methyluronamide (IB-MECA) and related A3 adenosine receptor ligands: peroxisome proliferator activated receptor (PPAR) ${\gamma}$ partial agonist and $PPAR{\delta}$ antagonist activity suggests their antidiabetic potential. J. Med. Chem. 60, 7459-7475. https://doi.org/10.1021/acs.jmedchem.7b00805
  36. Zhang, H., Xu, X., Chen, L., Chen, J., Hu, L., Jiang, H. and Shen, X. (2011) Molecular determinants of magnolol targeting both $RXR{\alpha}$ and $PPAR{\gamma}$. PLoS ONE 6, e28253. https://doi.org/10.1371/journal.pone.0028253

피인용 문헌

  1. Galangin 3-benzyl-5-methylether derivatives function as an adiponectin synthesis-promoting peroxisome proliferator-activated receptor γ partial agonist vol.54, 2020, https://doi.org/10.1016/j.bmc.2021.116564
  2. Sunscreen filter octocrylene is a potential obesogen by acting as a PPARγ partial agonist vol.355, 2020, https://doi.org/10.1016/j.toxlet.2021.12.001