The potential of citral isomers from lemongrass (Cymbopogon citratus) essential oil as WAT browning agents in obesity by activating AMPK and PPARγ: An in silico approach

Abstract

Obesity is characterized by abnormal fat accumulation in the white adipose tissue (WAT), posing a significant health risk. Enhancing energy expenditure through WAT browning using dietary components and natural extracts is a promising therapeutic strategy for obesity management. This study explored the efficacy of citral isomers from Cymbopogon citratus (lemongrass) essential oil as agents for WAT browning by activating primarily the proliferator-activated receptor gamma (PPARγ) and AMPK, utilizing an in silico approach. Essentials oil were extracted from lemongrass leaves and stalks via steam-hydro distillation, and the citral isomer content was analyzed through gas chromatography-mass spectrophotometry. Molecular docking was performed using AutoDock Vina, and molecular dynamics simulations were conducted using YASARA. Five citral isomers were identified: geranial, neral, geranial diethyl acetal (GDA), isogeranial, and isoneral isomers. This study identified GDA and neral as the most effective AMPK agonists, acting by directly activating their allosteric sites. Additionally, GDA, isoneral, and neral demonstrate PPARγ agonist properties by stabilising the protein’s active site. In conclusion, citral isomers in lemongrass essential oil hold the potential to act as WAT browning agents in obesity management through the activation of AMPK and PPARγ. Future in vitro and in vivo studies are required to validate these findings.