Understanding the neuroprotective effects of the rosemary phenolic diterpene carnosic acid (CA) has attracted increasing attention. We explored the mechanism by which CA modulates the neurotoxic effects of 6-hydroxydopamine (6-OHDA) in SH-SY5Y cells. Cells were pretreated with CA for 12 h followed by treatment with 100 μM 6-OHDA for 12 or 24 h. Cell viability determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolim bromide (MTT) assay indicated that 0.1 to 1 μM CA dose-dependently attenuated the cell death induced by 6-OHDA, whereas the effect of 3-5 μM CA was weaker. CA at 1 μM suppressed the 6-OHDA-induced nuclear condensation, reactive oxygen species generation, and cleavage of caspase 3 and PARP. Immunoblots showed that the phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and p38 by 6-OHDA was reduced in the presence of CA. Incubation of cells with CA resulted in significant increases in the total glutathione (GSH) level and the protein expression of the γ-glutamylcysteine ligase catalytic subunit and modifier subunit. L-Buthionine-sulfoximine, an inhibitor of GSH synthesis, attenuated the effect of CA on cell death and apoptosis. Treatment with CA also led to an increase in nuclear factor erythroid-2 related factor 2 (Nrf2) activation, antioxidant response element (ARE)-luciferase reporter activity, and DNA binding to the ARE. Silencing of Nrf2 expression alleviated the reversal of p38 and JNK1/2 activation by CA. These results suggest that the attenuation of 6-OHDA-induced apoptosis by CA is associated with the Nrf2-driven synthesis of GSH, which in turn down-regulates the JNK and p38 signaling pathways. The CA compound may be a promising candidate for neuroprotection in Parkinson's disease.

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SummaryThe purpose of this study was to evaluate the impact of Monascus -fermented products (MP) as regards certain changes in behavior for SAMP8 mice. Both male and female SAMP8 mice were fed a 0.03% MP diet from 3 mo of age to 11 mo of age. The results indicated that the grading score of passive avoidance behavior was significantly lower in the MP diet groups than in the control diet groups in both male and female SAMP8 mice ( p Ͻ 0.05). The MP diet-augmented test-animal body weight, feed intake and feed efficiency did not differ significantly from the corresponding values for control mice. The MP diet-fed mouse group revealed significantly improved learning and memory as revealed by average escape-response testing score when comparing with control mice ( p Ͻ 0.05). Further, the level of serum triglyceride and total cholesterol for the MP-fed group were shown to be significantly lower than for the control group of SAMP8 mice at 11 mo of age. The test mice fed an MP diet appeared to be significantly lower in aging score than the control group ( p Ͻ 0.05). The MP diet-fed mouse group revealed significantly improved total antioxidation of liver. Subsequent to supplementation of SAMP8 mice diets with MP for a period of 8 mo, these MP-fed mice revealed significantly lower lipofuscin-cell numbers within the hippocampus ( p Ͻ 0.05). The results suggest that dietary supplementation with MP might improve both learning and memory behaviour, and retard the aging process for SAMP8 mice.