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BACKGROUND/OBJECTIVES@#Excessive alcohol consumption has harmful health effects, including alcohol hangovers and alcohol-related liver disease. Therefore, methods to accelerate the alcohol metabolism are needed. Laurus nobilis is a spice, flavoring agent, and traditional herbal medicine against various diseases. This study examined whether the standardized aqueous extract of L. nobilis leaves (LN) accelerates the alcohol metabolism and protects against liver damage in single-ethanol binge Sprague-Dawley (SD) rats.MATERIALS/METHODS: LN was administered orally to SD rats 1 h before ethanol administration (3 g/kg body weight [BW]) at 100 and 300 mg/kg BW. Blood samples were collected 0.5, 1, 2, and 4 h after ethanol administration. The livers were excised 1 h after ethanol administration to determine the hepatic enzyme activity. The alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in the liver tissue were measured. @*RESULTS@#LN decreased the serum ethanol and acetaldehyde levels in ethanol-administered rats. LN increased the hepatic ADH and ALDH activities but decreased the alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase activities in the ethanol-administered rats. In addition, LN inhibited lipid peroxidation and increased the activities of SOD and GPx. @*CONCLUSIONS@#LN modulates the mediators of various etiological effects of excessive alcohol consumption and enhances the alcohol metabolism and antioxidant activity, making it a potential candidate for hangover treatments.
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It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.
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Apoptose , Caspase 3 , Caspase 9 , Linhagem Celular , Proliferação de Células , Sobrevivência Celular , Cromatina , Cordyceps , Vesículas Extracelulares , Glioma , Métodos , FosforilaçãoRESUMO
Cordyceps species including Cordyceps bassiana are a notable anti-cancer dietary supplement. Previously, we identified several compounds with anti-cancer activity from the butanol fraction (Cb-BF) of Cordyceps bassiana. To expand the structural value of Cb-BF-derived anti-cancer drugs, we employed various chemical moieties to produce a novel Cb-BF-derived chemical derivative, KTH-13-amine-monophenyl [4-isopropyl-2-(1-phenylethyl) aniline (KTH-13-AMP)], which we tested for anti-cancer activity. KTH-13-AMP suppressed the proliferation of MDA-MB-231, HeLa, and C6 glioma cells. KTH-13-AMP also dose-dependently induced morphological changes in C6 glioma cells and time-dependently increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, the levels of the active full-length forms of caspase-3 and caspase-9 were increased. In contrast, the levels of total forms of caspases-3, caspase-8, caspase-9, and Bcl-2 were decreased in KTH-13-AMP treated-cells. We also confirmed that the phosphorylation of STAT3, Src, and PI3K/p85, which is linked to cell survival, was diminished by treatment with KTH-13-AMP. Therefore, these results strongly suggest that this compound can be used to guide the development of an anti-cancer drug or serve as a lead compound in forming another strong anti-proliferative agent.
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Apoptose , Caspase 3 , Caspase 8 , Caspase 9 , Sobrevivência Celular , Cordyceps , Suplementos Nutricionais , Glioma , FosforilaçãoRESUMO
Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor (NF)-kappaB, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.
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Aripiprazol , Apoptose , Transtorno Bipolar , Encéfalo , Caspase 3 , Sobrevivência Celular , Glioma , Fígado , Macrófagos , Óxido Nítrico , Esquizofrenia , Receptor 4 Toll-LikeRESUMO
The objective of this study was to investigate the calf death and analyse the causes of the mortality by based on medical records and autopsy findings during 10 years in a large dairy farm. Total of 1,361 calf born and 146 calf dead during the invested period. Mortality rate was 10.7% and showed the big difference by year-specific mortality from 2.8% (4 calves) to 19.2% (28 calves). The highest rate of mortality was 1 week age (18.5%, 27 calves) and followed by 2 week age (11.6%, 17 calves) and mortality of more old calf tended to be reduced. The death less than 4 weeks and 8 weeks of age of the entire mortality accounted for 41.1% (60/146 calves) and 70.0% (102/146 calves), respectively. Causes of calf death were digestive diseases (53.4%), respiratory diseases (17.1%), musculoskeletal disease (8.2%), and systemic disease (8.2%) in order. Specific causes of calf death was highest in enteritis (43.2%), followed by pneumonia (14.4%), sepsis (8.2%) and fractures (3.4%). Seasonally, most of calf death happened in winter (48.6%) and then fall (21.2%). This results showed that enteritis and pneumonia are the main reason of calf death but other reasons were involved in calf death on the based on autopsy finding. On going research relating factors of calf mortality is needed.
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Autopsia , Enterite , Coreia (Geográfico) , Prontuários Médicos , Doenças Musculoesqueléticas , Pneumonia , Estações do Ano , SepseRESUMO
The present study was carried out to investigate the effect of barley and barley bran contaminated with Fusarium spp on growth performance and feed efficiency of fattening and growing pigs. In experiment 1, total 48 fattening Landrace pigs were used in a fattening trial for 71 days. Pigs weighing around 75 kg were allocated into different substitution groups containing 0, 10, 20 and 30% of barley contaminated Fusarium spp. In experiment 2, total 16 growing Landrace pigs were used in a growing trial for 45 days. Pigs weighing around 29.4 kg were allocated into different substitution groups containing 0, 5, 10 and 20% of barley bran contaminated Fusarium spp. Mycotoxin concentrations of barley and barley bran contaminated with 30% Fusarium spp were 0.452 and 1.049 ppm for deoxynivalenol, 8.125 and 17.646 ppm for nivalenol and 0.023 and 0.029 ppm for zearalenone, respectively. In experiment 1, no differences were found in weight gain and feed intake between control group (0%) and 10 or 20% substitution groups, but in 30% substitution group, weight gain and feed intake were significantly lower (p < 0.05) than those in control group. After slaughtering, the extended haemorrhage of the fundus region in stomach was observed in 20 or 30% substitution groups. In experiment 2, weight gain and feed intake were not significantly different among treatment groups. After slaughtering of experimental pigs, the extended haemorrhage of the fundus region in stomach was observed in pigs fed diet with 20% substitution group. These results suggest that the feeding of diet with contaminated highly levels of Fusarium spp was negative effect on growth and feed efficiency in growing and fattening pig.