title: Neuroprotective effects of dimerumic acid and deferricoprogen from Monascus purpureus NTU 568-fermented rice against 6-hydroxydopamine-induced oxidative stress and apoptosis in differentiated pheochromocytoma PC-12 cells.
abstract: Context Oxidative stress plays a key role in neurodegenerative disorders, including Parkinson's disease (PD). Rice fermented with Monascus purpureus Went (Monascaceae) NTU 568 (red mould rice) was found to contain antioxidants, including dimerumic acid (DMA) and deferricoprogen (DFC). Objective The effects of DMA and DFC on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity and potential protective mechanisms in differentiated PC-12 pheochromocytoma cells were investigated. Materials and methods DMA (0-60 μM) or DFC (0-10 μM) was co-treated with 6-OHDA (200 μM, 24 h exposure) in differentiated PC-12 cells. Cell viability and intercellular reactive oxygen species (ROS) were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and 2',7'-dichlorofluorescein-diacetate (DCFH-DA) assays, respectively. Cell apoptosis was determined by DNA fragmentation analysis and propidium iodide staining by flow cytometry. Western blot analysis was used to measure the levels of cell protein expression. Results DMA and DFC significantly increased cell viability to 72% and 81% in 6-OHDA-induced differentiated PC-12 cell cultures, respectively. Furthermore, DMA and DFC reduced 6-OHDA-induced formation of extracellular and intercellular ROS by 25% and 20%, respectively, and decreased NADPH oxidase-2 expression in differentiated PC-12 cells. DMA and DFC inhibited 6-OHDA-induced apoptosis and decreased activation of caspase-3 via regulation of Bcl-2-associated X protein (Bax) and Bcl-2 protein expression in differentiated PC-12 cells. Conclusion DMA and DFC may protect against 6-OHDA toxicity by inhibiting ROS formation and apoptosis. These results showed that the metabolites from M. purpureus NTU 568 fermentation were potential therapeutic agents for PD induced by oxidative damage and should be encouraged for further research.
authors.affiliation: a Department of Biochemical Science and Technology , College of Life Science, National Taiwan University , Taipei , Taiwan ;
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Tseng
authors.affiliation: b SunWay Biotechnology Company , Taipei , Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Hsu
authors.affiliation: a Department of Biochemical Science and Technology , College of Life Science, National Taiwan University , Taipei , Taiwan ;
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Pan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D054659:Diketopiperazines / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005285:Fermentation; D006877:Hydroxamic Acids / Q000302:isolation & purification / Q000494:pharmacology*; D032741:Monascus / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D012275:Oryza / Q000378:metabolism / Q000382:microbiology*; D018384:Oxidative Stress / Q000187:drug effects*; D016627:Oxidopamine / Q000633:toxicity*; D016716:PC12 Cells; D008517:Phytotherapy; D010879:Piperazines / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D054659:Diketopiperazines; D006877:Hydroxamic Acids; D018696:Neuroprotective Agents; D010879:Piperazines; D017382:Reactive Oxygen Species; C576795:deferricoprogen; C001011:dimerum acid; D016627:Oxidopamine
keywords: Antioxidants; Parkinson’s disease; red mould rice