Next Article in Journal
Study of the Performance of Particles Based on Modified Starches Containing Potassium Sorbate and Incorporated into Biodegradable Films: Physicochemical Characterization and Antimicrobial Action
Previous Article in Journal
Catalytic Converters for Vehicle Exhaust: Fundamental Aspects and Technology Overview for Newcomers to the Field
 
 
Article

Two Types of PPARγ Ligands Identified in the Extract of Artemisia campestris

1
Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan
2
Master’s/Doctoral Program in Life Science Innovation, School of Integrative and Global Majors, University of Tsukuba, Ibaraki 305-8572, Japan
3
Faculty of Life and Environmental Sciences, University of Tsukuba, Ibaraki 305-8572, Japan
4
Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Ibaraki 305-8572, Japan
5
Arid Zone Research Institute (IRA), Médenine 4119, Tunisia
6
Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: George O’Doherty
Chemistry 2021, 3(2), 647-657; https://doi.org/10.3390/chemistry3020045
Received: 23 April 2021 / Revised: 18 May 2021 / Accepted: 19 May 2021 / Published: 23 May 2021
(This article belongs to the Section Biological and Natural Products)
The 70% ethanol extract of Artemisia campestris was screened to find PPARγ ligands using the PPARγ ligand-responsive chimera luciferase reporter system. Capillartemisin B was identified as a PPARγ ligand that stimulated lipid accumulation in 3T3-L1 cells. By further purification of PPARγ ligands from a large-scale preparation of the methanol extract of Artemisia campestris, we isolated and identified eupatilin and santaflavone as PPARγ ligands. Weak PPARγ ligand activity of eupatilin or santaflavone in reporter assay was enhanced by a PPARγ antagonist, GW9662, suggesting that santaflavone or eupatilin and GW9662 bound simultaneously to the multiple sub-pockets of the PPARγ ligand-binding domain (LBD) and cooperatively activated PPARγ. Docking simulation suggested that eupatilin binds to the Ω-pocket but not to the AF-2 pocket of Y-shaped PPARγ LBD where artepillin C that differs from capillartemisin B at the C-5′ position without hydroxy group binds. Eupatilin or santaflavone with or without GW9662 did not stimulate lipid accumulation in differentiated 3T3-L1 cells, suggesting that binding of each compound alone or with GW9662 to the Ω-pocket which stimulated the PPARγ-responsive reporter expression was not enough to stimulate lipid accumulation. The PPARγ ligands found in this study have a potential to design the fragment-based drug design of a novel PPARγ ligand that cover the Y-shaped PPARγ LBD. View Full-Text
Keywords: PPARγ ligand; lipid accumulation; cooperative activation; ligand binding pocket; docking simulation PPARγ ligand; lipid accumulation; cooperative activation; ligand binding pocket; docking simulation
Show Figures

Figure 1

MDPI and ACS Style

Hasegawa, T.; Osaka, M.; Miyamae, Y.; Nishino, K.; Isoda, H.; Kawada, K.; Neffati, M.; Irie, K.; Nagao, M. Two Types of PPARγ Ligands Identified in the Extract of Artemisia campestris. Chemistry 2021, 3, 647-657. https://doi.org/10.3390/chemistry3020045

AMA Style

Hasegawa T, Osaka M, Miyamae Y, Nishino K, Isoda H, Kawada K, Neffati M, Irie K, Nagao M. Two Types of PPARγ Ligands Identified in the Extract of Artemisia campestris. Chemistry. 2021; 3(2):647-657. https://doi.org/10.3390/chemistry3020045

Chicago/Turabian Style

Hasegawa, Tokio, Mayo Osaka, Yusaku Miyamae, Katsutoshi Nishino, Hiroko Isoda, Kiyokazu Kawada, Mohamed Neffati, Kazuhiro Irie, and Masaya Nagao. 2021. "Two Types of PPARγ Ligands Identified in the Extract of Artemisia campestris" Chemistry 3, no. 2: 647-657. https://doi.org/10.3390/chemistry3020045

Find Other Styles

Article Access Map by Country/Region

1
Back to TopTop