2,4,5-Trimethoxybenzaldehyde, a Bitter Principle in Plants, Suppresses Adipogenesis through the Regulation of ERK1

Abstract

Because of the prevalence of obesity, there is particular interest in finding potential therapeutic targets. In a previous study, we demonstrated that 2,4,5-trimethoxybenzaldehyde (2,4,5-TMBA), a bitter principle in plants and a natural cyclooxygenase II (COX-2) inhibitor, suppressed the differentiation of preadipocyts into adipocytes at the concentration of 0.5 mM. In this current study, we aimed to investigate the stage during adipogenesis that is critically affected by 2,4,5-TMBA and the effects of 2,4,5-TMBA on the time-course expression of signaling molecules MAP kinase kinase (MAPKK, represented by MEK) and extracellular signal-regulated kinase (ERK), transcription factors CCAAT/enhancer binding protein (C/EBP)α, β, and δ and peroxisome proliferator-activated receptor (PPAR)γ, lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), and lipid droplet-coating protein perilipin A. When preadipocytes were co-cultured with 2,4,5-TMBA (0.5 mM) specifically at post-induction days 0-2, 2-4, 4-6, or 6-8 only, relative lipid accumulation was decreased by 67.93, 34.65, 49.56, and 34.32%, respectively. A time-course study showed that treatment of 2,4,5-TMBA suppressed the phosphorylation of ERK1 at the initial stage of adipogenesis but upregulated the phosphorylation at the late stage, which is opposite to the conditions required for the differentiation process. The overall expression of C/EBPα, β, and δ, PPARγ2, ACC, FAS, and perilipin A in preadipocytes was downregulated by the treatment of 2,4,5-TMBA. Taken together, our findings suggest that 2,4,5-TMBA suppresses adipogenesis through the regulation of ERK1 phosphorylation. Although results from in vitro studies cannot be directly extrapolated into clinical effects, our study will help to elucidate the anti-adipogenic potential of 2,4,5-TMBA.

N6-(2-Hydroxyethyl)adenosine in the Medicinal Mushroom Cordyceps cicadae Attenuates Lipopolysaccharide-Stimulated Pro-inflammatory Responses by Suppressing TLR4-Mediated NF-κB Signaling Pathways

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“…After striping, blocking and probing were performed as described above. 48 Statistical Analysis. All data were expressed as mean ± standard deviation.…”

Bazhu Decoction, a Traditional Chinese Medical Formula, Ameliorates Cognitive Deficits in the 5xFAD Mouse Model of Alzheimer’s Disease

“…Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro (Li et al, 2019). 2,4,5-trimethoxybenzaldehyde, a bitter principle in plants, suppresses adipogenesis through the regulation of ERK1 (Wang and Kuo, 2014). Physcion blocks cell cycle and induces apoptosis in human B cell precursor acute lymphoblastic leukemia cells by downregulating HOXA5 (Gao et al, 2017).…”