The Demethoxy Derivatives of Curcumin Exhibit Greater Differentiation Suppression in 3T3-L1 Adipocytes Than Curcumin: A Mechanistic Study of Adipogenesis and Molecular Docking

Abstract

Curcumin is a known anti-adipogenic agent for alleviating obesity and related disorders. Comprehensive comparisons of the anti-adipogenic activity of curcumin with other curcuminoids is minimal. This study compared adipogenesis inhibition with curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), and their underlying mechanisms. We differentiated 3T3-L1 cells in the presence of curcuminoids, to determine lipid accumulation and triglyceride (TG) production. The expression of adipogenic transcription factors and lipogenic proteins was analyzed by Western blot. A significant reduction in Oil red O (ORO) staining was observed in the cells treated with curcuminoids at 20 μM. Inhibition was increased in the order of curcumin < DMC < BDMC. A similar trend was observed in the detection of intracellular TG. Curcuminoids suppressed differentiation by downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), leading to the downregulation of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). AMP-activated protein kinase α (AMPKα) phosphorylation was also activated by BDMC. Curcuminoids reduced the release of proinflammatory cytokines and leptin in 3T3-L1 cells in a dose-dependent manner, with BDMC showing the greatest potency. BDMC at 20 μM significantly decreased leptin by 72% compared with differentiated controls. Molecular docking computation indicated that curcuminoids, despite having structural similarity, had different interaction positions to PPARγ, C/EBPα, and ACC. The docking profiles suggested a possible interaction of curcuminoids with C/EBPα and ACC, to directly inhibit their expression.

Evaluating the Therapeutic Potential of Curcumin and Synthetic Derivatives: A Computational Approach to Anti-Obesity Treatments

“…This is speculated to result from the structural similarity shared by curcumin and its derivatives. One study suggested that curcumin analogs interact with PPARγ to suppress adipogenesis more effectively than curcumin [ 73 ]. This implies that derivatives of curcumin may outperform curcumin in targeting the PPARγ isoform regulating adipogenesis, while activating the PPARγ isoform associated with inflammation and lipid metabolism suppression.…”

Effects of turmeric extract supplementation on the lipid and lipoprotein subfraction profile in hemodialysis patients: A randomised, double‐blind, crossover and controlled trial

“…Also, the proposed mechanism for the reduction of triglyceride levels after curcumin supplementation is that curcuminoids promote down‐regulation of peroxisome proliferator‐activated receptor γ expression (PPARγ) and CCAAT/enhancer‐binding protein α (C/EBPα), leading to the reduction of acetyl‐CoA carboxylase and fatty acid synthase enzymes (Alalaiwe et al, 2021).…”

“…(C/EBPα), leading to the reduction of acetyl-CoA carboxylase and fatty acid synthase enzymes (Alalaiwe et al, 2021).…”

Facile adipocyte uptake and liver/adipose tissue delivery of conjugated linoleic acid-loaded tocol nanocarriers for a synergistic anti-adipogenesis effect

“…α-Tocopherol, LA, or CLA (1‒500 µM) in free and nanoparticulate forms were added to the wells for a 24-h treatment. Then, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) at 0.5 mg/ml was added to the wells for 2 h. The other procedures were the same as previously reported [ 20 ].…”