Synergistic Interaction of Cinnamic Acid Derivatives With Commercial Oral Antidiabetic Drugs

Background: Cinnamic acid derivatives are naturally occurring substances found in fruits, vegetables, and flowers and are consumed as dietary phenolic compounds. Objectives: The effect of cinnamic acid, ferulic acid, coumaric acid, eugenol, chlorogenic acid and caffeic acid, alone and in combination with two commercial oral hypoglycemic drugs (OHD), namely, thiazolidinedione (THZ) and metformin, on the uptake of 2-deoxy glucose (2DG) by 3T3-L1 adipocytes is studied. Methods: 2DG uptake assy has been performed through enzymatic method and the gene expression studies is performed through reverse transcriptase-PCR. All the phytochemicals other than cinnamic acid show synergistic interaction in 2DG uptake with both the OHDs. Results: THZ (20μM) in combination with ferulic acid (25μM) or coumaric acid (25μM) increases the 2DG uptake by 7 or 6.34-folds respectively with respect to control. Whereas, metformin (20μM) along with ferulic acid (25μM) or cinnamic acid (25μM) increases 2DG uptake by 6.45 or 5.87-folds respectively when compared to control. Cinnamic acid increased 2DG uptake via PPAR gamma pathway whereas the rest of the phytochemicals enhanced it via PI3K pathway. Phytochemicals were able to reduce the expressions of the fatty acid synthase and HMG CoA reductase genes indicating that these compounds may be able to reduce the secondary complications caused because of lipid accumulation. Conclusions: Our findings suggest that cinnamic acid derivatives may be beneficial for the treatment of diabetes mellitus, act as a supplement with commercial drug and may reduce the secondary complications caused by OHDs.