Oxidative stress is a major component of harmful cascades activated in neurodegenerative disorders. Coenzyme Q10 (CoQ10), an essential component in the mitochondrial respiratory chain, has recently gained attention for its potential role in the treatment of neurodegenerative disease. Here, we investigated the possible protective effects of CoQ10 on H2O2-induced neurotoxicity in PC12 cells and the underlying mechanism. CoQ10 showed high free radical-scavenging activity as measured by a DPPH and TEAC. Pre-treatment of cells with CoQ10 diminished intracellular generation of ROS in response to H2O2. H2O2 decreased viability of PC12 cells which was reversed by pretreatment with CoQ10 according to MTT assay. H2O2-induced lipid peroxidation was attenuated by CoQ10 as shown by inhibition of MDA formation. Furthermore, pre-incubation of the cells with CoQ10 also restored the activity of cellular antioxidant enzymes which had been altered by H2O2. Moreover, CoQ10 induced Nrf2 nuclear translocation, the upstream of antioxidant enzymes. These findings suggest CoQ10 augments cellular antioxidant defense capacity through both intrinsic free radical-scavenging activity and activation of Nrf2 and subsequently antioxidant enzymes induction, thereby protecting the PC12 cells from H2O2-induced oxidative cytotoxicity.
Adenanthin, a natural ent-kaurane diterpenoid extracted from the herb Isodon adenantha, has been reported to increase intracellular reactive oxygen species in leukemic and hepatocellular carcinoma cells. However, the function and mechanism of the compound in adipogenesis and the development of obesity is still unknown. In this study, we demonstrated that adenanthin inhibited adipogenesis of 3T3-L1 and mouse embryonic fibroblasts, and the underlying mechanism included two processes: a delayed mitotic clonal expansion via G0/G1 cell cycle arrest by inhibiting the RB-E2F1 signaling pathway and a reduced C/EBPβ signaling by inhibiting the expression and activity of C/EBPβ during mitotic clonal expansion. Furthermore, adenanthin significantly reduced the growing body weight and adipose tissue mass during high-fat diet-inducing obesity of mice, indicating the beneficial effects of adenanthin as a potential agent for prevention of obesity.
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