ABSTRACT
Zinc plays a pivotal role in the function of cells and can induce apoptosis in various cancer cells, including Raji B lymphoma. However, the metabolic mechanism of Zn-induced apoptosis in Raji cells has not been explored. In this study, we performed global metabolic profiling using UPLC-Orbitrap-MS to assess the apoptosis of Raji cells induced by Zn ions released from ZnO nanorods. Multivariate analysis and database searches identified altered metabolites. Furthermore, the differences in the phosphorylation of 1380 proteins were also evaluated by Full Moon kinase array to discover the protein associated Zn-induced apoptosis. From the results, a prominent increase in glycerophosphocholine and fatty acids was observed after Zn ion treatment, but only arachidonic acid was shown to induce apoptosis. The kinase array revealed that the phosphorylation of p53, GTPase activation protein, CaMK2a, PPAR-γ, and PLA-2 was changed. From the pathway analysis, metabolic changes showed earlier onset than protein signaling, which were related to choline metabolism. LC-MS analysis was used to quantify the intracellular choline concentration, which decreased after Zn treatment, which may be related to the choline consumption required to produce choline-containing metabolites. Overall, we found that choline metabolism plays an important role in Zn-induced Raji cell apoptosis.
ABSTRACT
Morin displayed significant inhibition of chick chorioallantoic membrane (CAM) angiogenesis and was able to increase the endostatin level in human umbilical vein endothelial cells (HUVECs). Morin was shown to contain an in vivo anti-inflammatory activity using a carrageenan-induced air pouch model in mice. Antinociceptive activity of morin was also assessed using an acetic acid-induced writhing test in mice. Collectively, morin possesses antiangiogenic, in vivo anti-inflammatory, and antinociceptive activities.
Subject(s)
Analgesics/pharmacology , Angiogenesis Inhibitors/pharmacology , Anti-Inflammatory Agents/pharmacology , Flavonoids/pharmacology , Phytotherapy , Plant Extracts/pharmacology , Acetic Acid , Analgesics/therapeutic use , Angiogenesis Inhibitors/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Behavior, Animal/drug effects , Carrageenan , Cell Line , Chick Embryo , Chorioallantoic Membrane/blood supply , Chorioallantoic Membrane/drug effects , Disease Models, Animal , Endostatins/blood , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Flavonoids/therapeutic use , Humans , Inflammation/drug therapy , Maclura/chemistry , Male , Mice , Mice, Inbred ICR , Pain/drug therapy , Psidium/chemistry , Umbilical VeinsABSTRACT
This study aimed to elucidate the anti-inflammatory and related activities of mushroom Phellinus linteus. The results show that the EtOH extract of Phellinus linteus (PLE) dose-dependently inhibited the mouse ear edema induced by croton oil. Among PLE subfractions, the n-BuOH subfraction showed highest anti-inflammatory activity in croton oil-induced ear edema test. The n-BuOH subfraction also showed highest inhibitory activity on the chick embryo chorioallantoic membrane (CAM) angiogenesis in a dose-dependent manner. PLE could significantly reduce the number of writhing induced by acetic acid in mice, indicating that PLE possesses potent antinociceptive effect mediated by its anti-inflammatory activity. Mycelial extract of six different Phellinus strains were found to contain anti-angiogenic activity in the CAM assay. These results suggest that Phellinus linteus has anti-inflammatory and antinociceptive activities, in addition to its anti-angiogenic activity.
Subject(s)
Agaricales , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Butanols/therapeutic use , Edema/drug therapy , Animals , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Butanols/isolation & purification , Chick Embryo , Dose-Response Relationship, Drug , Male , Mice , Mice, Inbred ICR , Plant Extracts/isolation & purification , Plant Extracts/therapeutic useABSTRACT
Byakangelicin, 9-(2,3-dihydroxy-2-methylbutoxy)-4-methoxy-7H-furo[3,2-g][l]benzopyran-7-one (BKG), a component of Angelicae dahuricae Radix, is considered to be an inhibitor of aldose reductase for the treatment of diabetic cataract. An analytical method for the isolation of BKG developed by high-performance liquid chromatography has been reported. No literature on the metabolism of BKG, however, has been found. With the purpose of identifying new metabolites of BKG, BKG (100 mg/kg) was orally administered to Sprague-Dawley rats via a gavage. Using a metabolic cage, urine was collected for 24 h, and the urine samples were extracted by liquid-liquid extraction. For structural identification of new urinary metabolites of BKG, various instrumental analyses were conducted by gas-chromatography/mass spectrometry, high-performance liquid chromatography/diode array detector, liquid chromatography/mass spectroscopy with thermospray interface and 1H nuclear magnetic resonance spectroscopy. Two metabolites produced from the O-demethylation or O-dealkylation of BKG were newly identified, and another new but unknown metabolite was assumed to be the hydroxylated form of BKG. These results indicate that the major metabolic products of BKG are formed by O-demethylation or O-dealkylation of BKG side chains.
