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

Abstract

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 (PPARα and PPARγ), liver X receptor (LXR), glucose uptake, and lipid accumulation (adipogenesis). Activation of PPARα, PPARγ 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 µg/mL, AF caused 12.2-fold activation of PPARα and 5.7-fold activation of PPARγ, 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 μg/mL. It was concluded that AF acted as a PPARα/γ dual agonist without the undesired effect of adipogenesis and exhibited the property of enhancing glucose uptake. This is the first report to reveal the PPARα/γ 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.

Natural products for managing metabolic syndrome: a scoping review

“…Upon evaluating the results of the studies, it becomes evident that herbs play a significant role in addressing various aspects of metabolic syndrome. A wide array of herbs have demonstrated the capacity to directly influence key metabolic parameters such as blood pressure, blood glucose levels, lipid profiles, obesity, and cholesterol and triglyceride levels ( Nikaein et al, 2016 ; Seong et al, 2021 ; Amin et al, 2015 ; Belcaro et al, 2013 ; Devaraj et al, 2013 ; Najmi et al, 2013 ; Mansouri et al, 2012 ; Shah et al, 2012 ; Basu et al, 2010 ; Gupta Jain et al, 2017 ; Mopuri et al, 2018 ; Cicolari et al, 2020 ; Chae et al, 2022 ; Dobhal et al, 2022 ; Jakovljevic et al, 2018 ; Reshidan et al, 2019 ; Verhoeven et al, 2015 ; Gurrola-Dlaz et al, 2010 ; Benkhaled et al, 2022 ; Li et al, 2020 ; Hermans et al, 2020 ; De Martin et al, 2018 ; Mayer et al, 2022 ; Kasabri et al, 2014 ; Tan et al, 2011 ; Kuate et al, 2015 ; Kho et al, 2016 ). However, while the breadth of herbs studied is extensive, evaluations reveal variations in their efficacy and mechanisms of action.…”

Capsiate-Rich Fraction of Capsicum annuum Induces Muscular Glucose Uptake, Ameliorates Rosiglitazone-Induced Adipogenesis, and Exhibits Activation of NRs Regulating Multiple Signaling Pathways

“…Since a significant induction of PPARs by CE, CR, and Ca was observed, we investigated whether they also increased muscular glucose uptake by enhancing insulin sensitivity. For this purpose, a glucose uptake assay was carried out in differentiated myoblasts (C2C12 cells). , As shown in Table , treatments of CE (250 μg/mL), CR (250 μg/mL), and Ca (100 μM) resulted in 39.1, 44.7, 34.2, and 30.1% increase, respectively, in glucose uptake by muscle cells as compared to the vehicle control. Representative images and quantitations of 2-NBDG uptake (ng/mL) are shown in Figure .…”

“…The adipocyte differentiation assay was carried out as described by us earlier. , Briefly, preadipocytes (3T3-L1 cells) were seeded in 48-well plates at a density of 2 × 10 4 cells/well and maintained until 2 days postconfluence. After 2 days of confluency, the medium was replaced with DMEM containing 10% FBS, 10 μg/mL insulin, 1 μM dexamethasone, IBMX, and test samples at various concentrations (day 2).…”

“…A series of reporter gene assays for the determination of PPARα, PPARγ, LXR, and NRF2 agonistic effects were carried out in HepG2 cells as described previously with some modifications. − In brief, the cells were transfected with either pSG5-PPARα and PPRE X3-tk-luc or pCMV-rPPARγ and pPPREaP2-tk-luc or pCMX-hLXRα and LXRE-tk-luc or NQO1-ARE plasmid DNA (25 μg of each/1.5 mL cell suspension) by electroporation at 160 V for a single 70 ms pulse using BTX disposable cuvettes with a Square electroporator T820 (BTX, San Diego, CA). The transfected cells were plated at a density of 5 × 10 4 cells/well in 96-well tissue culture plates and grown for 24 h. After 24 h, the cells were treated with CE (500 μg/mL), CR (100 μg/mL), Ca (25, 50, 100 μM), ciprofibrate (10 μM), rosiglitazone (10 μM), T0901317 (25 nM), or curcumin (10 μM).…”

“…Myogenic differentiation of C2C12 cells was performed in 24-well plates as previously described. , For the glucose uptake assay, differentiated cells were treated with or without 2-NBDG (50 μg/mL) or with 2-NBDG and the desired concentrations of CE, CR, Ca, or rosiglitazone as a positive control (10 μM) for 24 h in glucose- and serum-free medium. Subsequently, the cell culture medium was removed, and cells were washed twice with ice-cold PBS.…”