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.
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Hirofumi
H
Inoue
Mari
M
Maeda-Yamamoto
Atsushi
A
Nesumi
Akira
A
Murakami
D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002392:Catechin / Q000009:adverse effects / Q000031:analogs & derivatives*; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005697:Galactosides / Q000494:pharmacology / Q000627:therapeutic use; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D000872:Anthocyanins; D000975:Antioxidants; D005697:Galactosides; D018840:HSP70 Heat-Shock Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; D002392:Catechin; C045651:epigallocatechin gallate; D051547:Heme Oxygenase-1; C017185:delphinidin