Cinnamaldehyde and paeonol increase HIF-1α Activity in proximal tubular epithelial cells under hypoxia

Hypoxia of renal tissue has recently been considered the common final pathway leading to end-stage renal failure in chronic renal failure. Our last study demonstrated that the Kampo formula hachimijiogan might have a renal protective effect by the influence of hypoxia inducible factor (HIF). In this study, the active components of hachimijiogan and their mechanisms were studied using a rat proximal tubular epithelial cell line cultured in hypoxic state. The eight crude drugs composing hachimijiogan were added to proximal tubular epithelial cells, and HIF-1α mRNA, its protein, and its downstream target genes, vascular endothelial growth factor (VEGF) and glucose transporter 1 (Glut-1) mRNA were measured. The results were that Cinnamomi Cortex and Moutan Cortex increased HIF-1α protein, VEGF and Glut-1 mRNA when cultured for 6 hours, without increasing HIF-1α mRNA. Furthermore, cinnamaldehyde and paeonol, the main integrants of Cinnamomi Cortex and Moutan Cortex, respectively, also increased HIF-1α protein, VEGF and Glut-1 mRNA. Because the expression of HIF-1α mRNA did not increase but the level of HIF-1α protein increased when treated by cinnamaldehyde and paeonol, their mechanisms were thought to inhibit the decomposition of HIF-1α protein.