A Multitarget Approach to Evaluate the Efficacy of Aquilaria sinensis Flower Extract against Metabolic Syndrome

Aquilaria sinensis (Lour.) Spreng is known for its resinous secretion (agarwood), often secreted in defense against injuries. We investigated the effects of A. sinensis flower extract (AF) on peroxisome proliferator-activated receptors alpha and gamma (PPAR alpha and PPAR gamma), liver X receptor (LXR), glucose uptake, and lipid accumulation (adipogenesis). Activation of PPAR alpha, PPAR gamma and LXR was determined in hepatic (HepG2) cells by reporter gene assays. Glucose uptake was determined in differentiated muscle (C2C12) cells using 2-NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose). Adipogenesis was determined in adipocytes (3T3-L1 cells) by Oil red O staining. At a concentration of 50 mu g/mL, AF caused 12.2-fold activation of PPAR alpha and 5.7-fold activation of PPAR gamma, while the activation of LXR was only 1.7-fold. AF inhibited (28%) the adipogenic effect induced by rosiglitazone in adipocytes and increased glucose uptake (32.8%) in muscle cells at 50 mu g/mL. It was concluded that AF acted as a PPAR alpha/gamma dual agonist without the undesired effect of adipogenesis and exhibited the property of enhancing glucose uptake. This is the first report to reveal the PPAR alpha/gamma dual agonistic action and glucose uptake enhancing property of AF along with its antiadipogenic effect, indicating its potential in ameliorating the symptoms of metabolic syndrome.