Cinnamon and its extracts have been used as herbal remedies for many ailments, including for reducing insulin resistance and diabetes complications. Type 2 diabetes mellitus (T2DM) is a rapidly growing health concern around the world. Although many drugs are available for T2DM treatment, side effects and costs can be considerable, and there is increasing interest in natural products for managing chronic health conditions. Cinnamon may decrease the expression of genes associated with T2DM risk. The purpose of this study was to evaluate the effects of cinnamon water extract (CWE) compared with metformin on T2DM-related gene expression. HepG2 human hepatoma cells, widely used in drug metabolism and hepatotoxicity studies, were treated with different concentrations of metformin or CWE for 24 or 48 h. Cell viability was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and glucose uptake was compared in untreated and CWE-or metformin-treated cells under highglucose conditions. Finally, total RNA was extracted and analyzed by RNA sequencing (RNA-seq), and bioinformatics analyses were performed to compare the transcriptional effects of CWE and metformin. We found cell viability was better in cells treated with CWE than in metformin-treated cells, demonstrating that CWE was not toxic at tested doses. CWE significantly increased glucose uptake in HepG2 cells, to the same degree as metformin (1.4-fold). RNA-seq data revealed CWE and metformin both induced significantly increased (1.3-to 1.4-fold) glucose uptake gene expression compared with untreated controls. Transcriptional differences between CWE and metformin were not significant. The effects of 0.125 mg mL −1 CWE on gene expression were comparable to 1.5 mg mL −1 (9.5 mM) metformin. In addition, gene expression at 0.125 mg mL −1 CWE was comparable to 1.5 mg mL −1 (9.5 mM) metformin. Our results reveal that CWE's effects on cell viability, glucose uptake, and gene expression in HepG2 cells are comparable to those of metformin, suggesting CWE may be an effective dietary supplement for mitigating T2DMrelated metabolic dysfunction.
Cinnamon and its extracts have been used herbal remedies including reducing insulin resistance and diabetic complications. T2DM is a rapidly growing health concern around the world[[1]](#ref-0001). While many drugs are now available for T2DM treatment, side effects and costs can be considerable, and there is increasing interest in natural products for managing chronic health conditions[2]. Cinnamon may decrease the expression of genes associated with type 2 diabetes (T2DM) risk. The purpose of this study was to evaluate the effects of cinnamon water extract (CWE) and metformin on T2DM-related gene expression. The HepG2 human hepatoma cell line is widely used in drug metabolism and hepatotoxicity studies. HepG2 cells were treated with different concentrations of metformin or CWE for 24 or 48 h. Cell viability was assessed by MTT assay, and glucose uptake was compared between untreated and CWE- or metformin-treated cells under high-glucose conditions. Finally, total RNA was extracted and analyzed by RNA sequencing (RNA-Seq), and bioinformatics analysis was performed to compare the transcriptional effects of CWE and metformin. We found that cell viability was higher in cells treated with CWE than in metformin-treated cells, demonstrating that the cinnamon extract was not toxic at the tested doses. CWE significantly increased glucose uptake in HepG2 cells to the same degree as metformin (1.4-fold). RNA-Seq data revealed that CWE and metformin both induced significant changes (1.3- to 1.4-fold increases) in glucose uptake gene expression compared with untreated controls, but that transcriptional differences between CWE and metformin conditions were not significant. The effects of 0.125 mg mL CWE on gene expression were comparable to those seen with 1.5 mg mL (9.5 mM) metformin. We found that gene expression at 0.125 mg mL-1 CWE was comparable to 1.5 mg mL-1 (9.5 mM) metformin. Our results reveal that CWE’s effects on cell viability, glucose uptake, and gene expression in HepG2 cells are comparable to those of the widely used antidiabetic drug metformin, suggesting that CWE may be an effective dietary supplement for mitigating T2DM-related metabolic dysfunction.
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