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1.
J Surg Res ; 222: 39-47, 2018 02.
Article in English | MEDLINE | ID: mdl-29273374

ABSTRACT

BACKGROUND: Reactive oxygen species are increased in multiple gastrointestinal diseases and contribute to their pathogenesis. glutathione (GSH) is an antioxidant that helps to prevent reactive oxygen species-mediated mucosal damage. This study examines the mechanisms by which GSH attenuates hydrogen peroxide (H2O2)-induced injury in intestinal epithelial cells. METHODS: IEC-6 cells were cultured and treated with H2O2 ± GSH. Inflammation was measured by nuclear factor kappa-B (NF-κB) P65 expression, NF-κB nuclear translocation, iκBα phosphorylation, and interleukin 1 beta secretion. Terminal deoxynucleotidyl transferase-mediated UTP end-labeling staining and cleaved caspase-3 were used to assess apoptosis. The role of P38 mitogen-activated protein kinase (P38 MAPK) signaling was examined using the P38 MAPK agonist U46619 and inhibitor SB203580 in H2O2 and GSH-treated cells. Phosphorylated and total P38 MAPKs and cleaved caspase-3 were measured by Western blot. Data are means ± standard deviation, statistical significance P < 0.05 by student's t-test, or one-way analysis of variance. RESULTS: Pretreatment with GSH attenuates the activation of NF-κB and P38 MAPK signaling pathways by H2O2. GSH also decreased H2O2-mediated increases in interleukin 1 beta secretion, cleaved caspase-3 activation, and apoptosis in IEC-6 cells. SB203580 attenuated the increase in apoptosis and cleaved caspase-3 in H2O2-treated cells. The increase in apoptotic index and cleaved caspase-3 observed in U46619-treated cells was also diminished by GSH. CONCLUSIONS: GSH appears to ameliorate oxidative injury in intestinal epithelial cells by attenuating H2O2-mediated activation of NF-κB and P38 MAPK signaling pathways that regulate intestinal inflammation and apoptosis.


Subject(s)
Glutathione/pharmacology , Intestinal Mucosa/drug effects , Oxidative Stress/drug effects , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid , Animals , Apoptosis/drug effects , Cell Line , Drug Evaluation, Preclinical , Glutathione/therapeutic use , Hydrogen Peroxide , Interleukin-1beta/metabolism , Intestinal Diseases/prevention & control , Intestinal Mucosa/metabolism , MAP Kinase Signaling System/drug effects , NF-kappa B/metabolism , Rats , Sesquiterpenes
2.
J Asian Nat Prod Res ; 18(7): 669-76, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26982333

ABSTRACT

Two new 28-nor-oleanane-type triterpene saponins, oleiferoside U (1), and oleiferoside V (2) were isolated from the 50% EtOH extract of the roots of Camellia oleifera C. Abel. Their structures were elucidated as camellenodiol 3ß-O-ß-d-galactopyranosyl-(1→2)-ß-d-xylopyranosyl-(1→2)-[ß-d-galactopyranosyl-(1→3)]-ß-d-glucuronopyranoside and camellenodiol 3ß-O-ß-d-galactopyranosyl-(1→3)-ß-d-xylopyranosyl-(1→2)-[ß-d-galactopyranosyl-(1→3)]-ß-d-glucuronopyranoside. Their chemical structures were established mainly on the basis of integrated spectroscopic techniques. In vitro, cytotoxic activities of the two new triterpene saponins were evaluated against three human tumor cell lines (A549, SMMC-7721, and MCF-7) using the MTT assay. Both of them showed a certain cytotoxic activities toward the tested cell lines and gave IC50 values in the range of 45.04-63.22 µM.


Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Camellia/chemistry , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Oleanolic Acid/analogs & derivatives , Saponins/isolation & purification , Saponins/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Humans , Inhibitory Concentration 50 , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Oleanolic Acid/chemistry , Oleanolic Acid/isolation & purification , Oleanolic Acid/pharmacology , Plant Roots/chemistry , Saponins/chemistry
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