Delphinidin-3-O-galactoside protects mouse hepatocytes from (−)-epigallocatechin-3-gallate-induced cytotoxicity via up-regulation of heme oxygenase-1 and heat shock protein 70

Delphinidin-3-O-galactoside (D3G) is a water-soluble anthocyanin with antioxidant activity. (−)-Epigallocatechin-3-gallate (EGCG) is also known as a powerful antioxidant but concomitantly possesses a prooxidative property. We hypothesized that D3G is capable of protecting the EGCG-induced cytotoxicity and endoplasmic reticulum (ER) stress via inducing self-protective proteins and antioxidant enzymes. (−)-Epigallocatechin-3-gallate (200-500 μM) dose dependently decreased the viability of hepa1c1c-7 mouse hepatocytes, whereas D3G (50-500 μM) did not change it. Pretreatment with D3G significantly suppressed EGCG-induced cytotoxicity in a time-dependent manner (0, 6, and 24 hours). (−)-Epigallocatechin-3-gallate drastically decreased heme oxygenase-1 and heat shock protein 70 messenger RNA (mRNA) levels, whereas, pretreatment with D3G markedly attenuated their down-regulations. Delphinidin-3-O-galactoside remarkably decreased EGCG-induced ER stress responses such as C/EBP-homologus protein mRNA expression and X-box-binding protein-1 mRNA splicing. Taken together, our data suggest that D3G is capable of masking the EGCG-induced cytotoxicity and ER stress, presumably through up-regulation of antioxidant enzymes and heat shock proteins.