Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2019.180
Diallyl Biphenyl-Type Neolignans Have a Pharmacophore of PPARα/γ Dual Modulators
Yujia Han1,†, Jingjing Liu1,†, Sungjin Ahn1 , Seungchan An1 , Hyejin Ko1 , Jeayoung C. Shin1 , Sun Hee Jin1 , Min Won Ki1 , So Hun Lee2 , Kang Hyuk Lee2 , Song Seok Shin2 , Won Jun Choi3 and Minsoo Noh1,*
1 College of Pharmacy and Natural Products Research Institute, Seoul National University, Seoul 08826,
2 SK Bioland, Cheongju 28162,
3 College of Pharmacy, Dongguk University, Goyang 10326, Republic of Korea
E-mail: minsoonoh@snu.ac.kr
Tel: +82-2-880-2481, Fax: +82-2-880-2482
The first two authors contributed equally to this work.
Received: October 29, 2019; Revised: December 24, 2019; Accepted: January 7, 2020; Published online: June 24, 2020.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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: Diallyl biphenyl-type neolignans, Adiponectin, Human bone marrow mesenchymal stem cells, Peroxisome proliferatoractivated receptor α/γ


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