Neuroprotective effects of dimerumic acid and deferricoprogen fromMonascus purpureusNTU 568-fermented rice against 6-hydroxydopamine-induced oxidative stress and apoptosis in differentiated pheochromocytoma PC-12 cells

Abstract

Pan (2016) Neuroprotective effects of dimerumic acid and deferricoprogen from Monascuspurpureus NTU 568-fermented rice against 6-hydroxydopamine-induced oxidative stress and apoptosis in differentiated pheochromocytoma PC-12 cells, Pharmaceutical Biology, 54:8, 1434-1444, DOI: 10.3109/13880209.2015 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 mM) or DFC (0-10 mM) was co-treated with 6-OHDA (200 mM, 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 0 ,7 0 -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-OHDAinduced 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. ARTICLE HISTORY

Metal Chelation Therapy and Parkinson’s Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs

“…Creatine [179,180] Cudraflavone B [181] Curcumin [89,117,[182][183][184] Cyanidin [185,186] D-512 [187] D-607 (bipyridyl-D2R/D3R agonist hybrid) [12,188,189] DA-2 (8D) [12,89] DA-3 [12] DA-4 [12] Dabigatran etexilate [190] Dabrafenib [191] (S)-3,4-DCPG [115] Deferasirox [24] Deferricoprogen [192] Delphinidin [160,185,193,194] Demethoxycurcumin [195] Dendropanax morbifera active compound [196] Desferrioxamine (Desferoxamine, Desferal, DFO) [112] (S)-N-(3-(3,6-Dibromo-9H -carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [197] 4,5-O-Dicaffeoyl-1-O-(malic acid methyl ester)-quinic acid derivatives (R1, R2, R3, R4, or R5 = caffeoyl) [198] Dihydromyricetin [199]…”

A Review of Fermented Foods with Beneficial Effects on Brain and Cognitive Function

“…RMR also contains multiple functional components derived from the fermentation process (38). The protective effect of RMR might be caused by a synergism among these multiple bioactive components (35,38,40). …”

The Prevention of Alzheimer's Disease and Parkinson’s Disease by Monascus purpureus NTU 568-Fermented Compounds

“…Research results show that in differentiated pheochromocytoma PC-12 cells treated with 6-OHDA, DMA, and DFC could suppress extracellular auto-oxidation and the formation of intracellular ROS through the downregulation of NOX-2 expression, and suppress the activation of caspase-3 by increasing Bcl2 expression and reducing Bax expression. Through these two mechanisms, DMA and DFC lower the number of apoptotic cells in 6-OHDA-induced differentiated PC-12 cells ( Figure 5) [14]. These results are significant for the development of anti-oxidation therapy for PD.…”

“…As functional foods are receiving increasing attention, Monascus fermented products, with their many physiological benefits are becoming important. As has been revealed in past research, fermentation products of Monascus and their extracts can effectively improve the course of AD and PD, possessing significant preventative and alleviating effects [7,[14][15][16][17][18][19]. The functional compounds are confirmed to be the novel yellow pigment monascin (MS) and ankaflavin (AK) for AD treatment, and novel antioxidative agent dimerumic acid (DMA) and deferricoprogen (DFC) for PD treatment.…”