RESUMEN
Prion diseases are neurodegenerative disorders in humans and animals for which no therapies are currently available. Here, we report that Curcuma phaeocaulis Valeton (Zingiberaceae) (CpV) extract was partly effective in decreasing prion aggregation and propagation in both in vitro and in vivo models. CpV extract inhibited self-aggregation of recombinant prion protein (PrP) in a test tube assay and decreased the accumulation of scrapie PrP (PrPSc) in ScN2a cells, a cultured neuroblastoma cell line with chronic prion infection, in a concentration-dependent manner. CpV extract also modified the course of the disease in mice inoculated with mouse-adapted scrapie prions, completely preventing the onset of prion disease in three of eight mice. Biochemical and neuropathological analyses revealed a statistically significant reduction in PrPSc accumulation, spongiosis, astrogliosis, and microglia activation in the brains of mice that avoided disease onset. Furthermore, PrPSc accumulation in the spleen of mice was also reduced. CpV extract precluded prion infection in cultured cells as demonstrated by the modified standard scrapie cell assay. This study suggests that CpV extract could contribute to investigating the modulation of prion propagation.
Asunto(s)
Enfermedades por Prión , Priones , Scrapie , Zingiberaceae , Animales , Ratones , Curcuma/metabolismo , Modelos Animales , Extractos Vegetales/farmacología , Enfermedades por Prión/tratamiento farmacológico , Proteínas Priónicas , Priones/metabolismo , Scrapie/metabolismo , OvinosRESUMEN
Skeletal muscle atrophy is associated with many diseases including cancer, inflammatory diseases, neuromuscular diseases, and acute critical illness. Justicia procumbens L. has been used as a herbal remedy, but the pharmacological effect of J. procumbens on muscle atrophy has not yet been reported. Herein, we investigate the anti-atrophic effect of the n-butanol fraction of J. procumbens (JPBuFr) on dexamethasone (DEX)-induced muscle atrophy in C2C12 myotubes. The myotubes diameter, MHC positive area, ROS production, and mitochondria contents were observed under a fluorescence microscope, and various proteins related to degradation or synthesis were analyzed by western blots. JPBuFr significantly attenuated a reduction of myotube diameter, mitochondrial content, ATP level, myosin heavy chain, and myogenin expression induced by DEX. Furthermore, co-treatment of DEX and JPBuFr not only increased phosphorylation of Akt, mTOR, and p70S6K proteins but also decreased reactive oxygen species production and expression of protein degradation factors (MuRF1, Atrogin-1, FoxO3a) compared to DEX treatment. These results suggest that JPBuFr may provide potential protective effects against muscle atrophy, giving it potential for the development of anti-atrophic health functional foods.
RESUMEN
Alpinia oxyphylla Miq. (Zingiberaceae) extract exerts protective activity against tert-butyl hydroperoxide-induced toxicity in HepG2 cells, and the antioxidant response element (ARE) luciferase activity increased 6-fold at 30 µg/mL in HepG2 cells transiently transfected with ARE-luciferase. To identify active molecules, activity-guided isolation of the crude extract led to four sesquiterpenes (1, 2, 5, 6) and two diarylheptanoids (3 and 4) from an n-hexane extract and six sesquiterpenes (7-12) from an ethyl acetate extract. Chemical structures were elucidated by one-dimensional, two-dimensional nuclear magnetic resonance (1D-, 2D-NMR), and mass (MS) spectral data. Among the isolated compounds, eudesma-3,11-dien-2-one (2) promoted the nuclear accumulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and increased the promoter property of the ARE. Diarylheptanoids, yakuchinone A (3), and 5'-hydroxyl-yakuchinone A (4) showed radical scavenging activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assays. Furthermore, optimization of extraction solvents (ratios of water and ethanol) was performed by comparison of contents of active compounds, ARE-inducing activity, radical scavenging activity, and HepG2 cell protective activity. As a result, 75% ethanol was the best solvent for the extraction of A. oxyphylla fruit. This study demonstrated that A. oxyphylla exerted antioxidant effects via the Nrf2/HO-1 (heme oxygenase-1) pathway and radical scavenging along with active markers eudesma-3,11-dien-2-one (2) and yakuchinone A (3).