Monascin from red mold dioscorea as a novel antidiabetic and antioxidative stress agent in rats and Caenorhabditis elegans
Resource
Free Radic Biol Med,52(1),109-17.
Journal
Free Radical Biology and Medicine
Journal Volume
52
Journal Issue
1
Pages
109-117
Date Issued
2012
Author(s)
Abstract
Monascin is a major yellow compound from red mold dioscorea. We investigated monascin to test whether this compound acts as an antidiabetic and antioxidative stress agent in diabetic rats and Caenorhabditis elegans. The mechanisms by which monascin exerts its action in vivo were also examined. Streptozotocin (STZ)-induced diabetic rats were given monascin at 30 mg/kg/day and sacrificed after 8 weeks. Blood glucose and serum insulin, triglyceride, total cholesterol, and high-density lipoprotein and antioxidative enzymes in the pancreas of rats were measured. In addition, monascin was evaluated for stress resistance and potential associated mechanisms in C. elegans. Throughout the 8-week experimental period, significantly lowered blood glucose, serum triglyceride, and total cholesterol and higher high-density lipoprotein levels were observed in monascin-treated rats. Monascin-treated rats showed higher serum insulin level, lower reactive oxygen species production, and higher activities of glutathione peroxidase, superoxide dismutase, and catalase in the pancreas compared to diabetic control rats. In addition, monascin significantly induced the hepatic mRNA levels of FOXO3a, FOXO1, MnSOD, and catalase in STZ-induced diabetic rats. Monascin-treated C. elegans showed an increased survival rate during oxidative stress and heat stress treatments compared to untreated controls. Moreover, monascin extended the life span under high-glucose conditions and enhanced expression of small heat shock protein (sHSP-16.2), superoxide dismutase (SOD-3), and glutathione S-transferase (GST-4) in C. elegans. Finally, we showed that monascin affected the subcellular distribution of the FOXO transcription factor DAF-16, whereas it was unable to enhance oxidative stress resistance in the daf-16 deletion mutant in C. elegans. Mechanistic studies in rats and C. elegans suggest that the protective effects of monascin are mediated via regulation of the FOXO/DAF-16-dependent insulin signaling pathway by inducing the expression of stress response/antioxidant genes, thereby enhancing oxidative stress resistance. ? 2011 Elsevier Inc.
Subjects
Antioxidant; Caenorhabditis elegans; Free radicals; Insulin signaling pathway; Monascin
SDGs
Other Subjects
antidiabetic agent; antioxidant; catalase; cholesterol; glucose; glutathione peroxidase; glutathione transferase; heat shock protein; high density lipoprotein; insulin; manganese superoxide dismutase; messenger RNA; monascin; superoxide dismutase; transcription factor DAF 16; transcription factor FKHR; transcription factor FKHRL1; triacylglycerol; unclassified drug; animal experiment; animal model; article; Caenorhabditis elegans; cholesterol blood level; controlled study; diabetes mellitus; drug mechanism; gene deletion; gene expression; gene mutation; glucose blood level; heat stress; insulin blood level; lifespan; male; nonhuman; oxidative stress; priority journal; rat; signal transduction; streptozocin diabetes; survival rate; treatment duration; triacylglycerol blood level; Animals; Antioxidants; Blood Glucose; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Catalase; Diabetes Mellitus, Experimental; Dioscorea; Forkhead Transcription Factors; Gene Expression; Glutathione Peroxidase; Glutathione Transferase; Heterocyclic Compounds, 3-Ring; Hypoglycemic Agents; Insulin; Lipoproteins, HDL; Male; Oxidative Stress; Pancreas; Rats; Reactive Oxygen Species; Signal Transduction; Superoxide Dismutase; Transcription Factors; Caenorhabditis elegans; Dioscorea; Rattus
Type
journal article