Palmitate-increased TGF-β1 Gene Expression and p-Smad2/3 Protein Levels Attenuated by Chicoric Acid in Patients with Type 2 Diabetes Mellitus.

The transforming growth factor beta1 (TGF-β1) signaling pathway plays a critical role in the pathogenesis of Type 2 diabetes mellitus (T2DM). Modulating this pathway may offer therapeutic benefits for managing T2DM. Chicoric acid (CA), a polyphenolic compound with reported anti-diabetic properties, has shown potential in metabolic regulation; however, its precise molecular mechanisms remain unclear. This study aimed to investigate the effects of palmitate and CA on the TGF-β1 signaling pathway in peripheral blood mononuclear cells (PBMCs) from newly diagnosed T2DM patients and healthy controls. A total of 40 participants, including 20 newly diagnosed T2DM patients and 20 age-matched healthy individuals (40-60 years), were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated and treated with palmitate and CA. The expression of TGF-β1 mRNA was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). Protein levels of Smad2/3 and phosphorylated Smad2/3 (p-Smad2/3) were assessed via western blot analysis. Palmitate stimulation significantly upregulated TGF-β1 gene expression and increased p-Smad2/3 protein levels in PBMCs. However, CA treatment effectively attenuated these palmitate-induced elevations in TGF-β1 expression and p-Smad2/3 protein levels. Additionally, a positive correlation was observed between TGF-β1 expression and p-Smad2/3 protein levels. These findings suggest that CA may act as an inhibitor of the TGF-β1 signaling pathway, potentially contributing to T2DM management by downregulating TGF-β1/Smad signaling. Further studies are warranted to explore its therapeutic potential in diabetes treatment.