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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)
  • Received : 2019.10.29
  • Accepted : 2020.01.07
  • Published : 2020.09.01

Abstract

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.

Keywords

Acknowledgement

This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HN14C0088) and the NRF grant funded by the Korea government (Ministry of Science and ICT) (NRF-2019R1A2C2085749).

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