Screening of new chemopreventive compounds from Digitalis purpurea.
Chemopreventive agents induce a battery of genes whose protein products can protect cells from chemical-induced carcinogenesis. In this study, we isolated four different glycosides (1 acteoside; 2 purpureaside A; 3 calceolarioside B; and 4, plantainoside D) from the leaves of Digitalis purpurea and studied their abilities to induce glutathione S-transferase (GST) and their protective efficiencies against aflatoxin B1-induced cytotoxicity in H4IIE cells. Of these four glycosides, acteoside significantly inhibited the cytotoxicity induced by aflatoxin B1 (AFB1) and also selectively increased GSTalpha protein levels. Reporter gene analysis using an antioxidant response element (ARE) containing construct and subcellular fractionation assays, revealed that GSTalpha induction by acteoside might be associated with Nrf2/ARE activation. The results suggest that acteoside possesses a potent hepatoprotective effect against AFB1 and that it can be applied as a potential chemopreventive agent.
Lee
J Y
JY
College of Pharmacy, Chosun University, Seosuk-dong, Dong-gu, Gwangju, South Korea.
Woo
E
E
Kang
K W
KW
D016604:Aflatoxin B1 / Q000037:antagonists & inhibitors / Q000633:toxicity; D016588:Anticarcinogenic Agents; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity; D002460:Cell Line; D004070:Digitalis / Q000737:chemistry*; D004071:Digitalis Glycosides / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018515:Plant Leaves / Q000737:chemistry; D021381:Protein Transport / Q000235:genetics
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004071:Digitalis Glycosides; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D016604:Aflatoxin B1; D008156:Luciferases; D005982:Glutathione Transferase