Cheonggukjang-Specific Component 1,3-Diphenyl-2-Propanone as a Novel PPARα/γ Dual Agonist: An In Vitro and In Silico Study

Abstract

Background: Cheonggukjang is a traditional fermented soybean paste that is mostly consumed in Korea. However, the biological activities of Cheonggukjang specific compounds have not been studied. Thus, we aimed to discover a novel dual agonist for PPARα/γ from dietary sources such as Cheonggukjang specific volatile compounds and explore the potential role of PPARα/γ dual agonists using in vitro and in silico tools. Methods: A total of 35 compounds were selected from non-fermented and fermented soybean products cultured with Bacillus subtilis, namely Cheonggukjang, for analysis by in vitro and in silico studies. Results: Molecular docking results showed that 1,3-diphenyl-2-propanone (DPP) had the lowest docking score for activating PPARα (1K7L) and PPARγ (3DZY) with non-toxic effects. Moreover, DPP significantly increased the transcriptional activities of both PPARα and PPARγ and highly activated its expression in Ac2F liver cells, in vitro. Here, we demonstrated for the first time that DPP can act as a dual agonist of PPARα/γ using in vitro and in silico tools. Conclusions: The Cheonggukjang-specific compound DPP could be a novel PPARα/γ dual agonist and it is warranted to determine the therapeutic potential of PPARα/γ activation by dietary intervention and/or supplementation in the treatment of metabolic disorders without causing any adverse effects.

Effect of Pesticides on Peroxisome Proliferator-Activated Receptors (PPARs) and Their Association with Obesity and Diabetes

“…These models revealed that for the PPARγ receptor, the amino acid residue Cys 285 could play a crucial role in the association of pesticides with this receptor, as observed for diflubenzuron [20] or for the organotin compounds TPT and TBT [21]. This interaction was also reported for molecules of a different type such as 1,3-diphenyl-2-propone, volatile organic compounds extracted from a fermented cheonggukjang (Korean food), and the Cys 285 residues of PPARβ/δ and PPARγ [111]. This interaction was confirmed by X-rays to be essential for the interaction between organotin and the PPARY [21].…”