Almoiliqy 2020 Acta Pharmacol Sin

[[Has title::Almoiliqy M, Wen J, Xu B, Sun YC, Lian MQ, Li YL, Qaed E, Al-Azab M, Chen DP, Shopit A, Wang L, Sun PY, Lin Y (2020) Cinnamaldehyde protects against rat intestinal ischemia/reperfusion injuries by synergistic inhibition of NF-κB and p53. Acta Pharmacol Sin 41:1208-22.]]

» [[Has info::PMID: 32238887]]

Was written by::Almoiliqy M, Was written by::Wen J, Was written by::Xu B, Was written by::Sun YC, Was written by::Lian MQ, Was written by::Li YL, Was written by::Qaed E, Was written by::Al-Azab M, Was written by::Chen DP, Was written by::Shopit A, Was written by::Wang L, Was written by::Sun PY, Was written by::Lin Y (Was published in year::2020) Was published in journal::Acta Pharmacol Sin

Abstract: [[has abstract::Our preliminary study shows that cinnamaldehyde (CA) could protect against intestinal ischemia/reperfusion (I/R) injuries, in which p53 and NF-κB p65 play a synergistic role. In this study, we conducted in vivo and in vitro experiments to verify this proposal. SD rats were pretreated with CA (10 or 40 mg · kg^-1 · d^-1, ig) for 3 days, then subjected to 1 h mesenteric ischemia followed by 2 h reperfusion. CA pretreatment dose-dependently ameliorated morphological damage and reduced inflammation evidenced by decreased TNF-α, IL-1β, and IL-6 levels and MPO activity in I/R-treated intestinal tissues. CA pretreatment also attenuated oxidative stress through restoring SOD, GSH, LDH, and MDA levels in I/R-treated intestinal tissues. Furthermore, CA pretreatment significantly reduced the expression of inflammation/apoptosis-related NF-κB p65, IKKβ, IK-α, and NF-κB p50, and downregulated apoptotic protein expression including p53, Bax, caspase-9 and caspase-3, and restoring Bcl-2, in I/R-treated intestinal tissues. We pretreated IEC-6 cells in vitro with CA for 24 h, followed by 4 h hypoxia and 3 h reoxygenation (H/R) incubation. Pretreatment with CA (3.125, 6.25, and 12.5 μmol · L^-1) significantly reversed H/R-induced reduction of IEC-6 cell viability. CA pretreatment significantly suppressed oxidative stress, NF-κB activation and apoptosis in H/R-treated IEC-6 cells. Moreover, CA pretreatment significantly reversed mitochondrial dysfunction in H/R-treated IEC-6 cells. CA pretreatment inhibited the nuclear translocation of p53 and NF-κB p65 in H/R-treated IEC-6 cells. Double knockdown or overexpression of p53 and NF-κB p65 caused a synergistic reduction or elevation of p53 compared with knockdown or overexpression of p53 or NF-κB p65 alone. In H/R-treated IEC-6 cells with double knockdown or overexpression of NF-κB p65 and p53, CA pretreatment caused neither further decrease nor increase of NF-κB p65 or p53 expression, suggesting that CA-induced synergistic inhibition on both NF-κB and p53 played a key role in ameliorating intestinal I/R injuries. Finally, we used immunoprecipitation assay to demonstrate an interaction between p53 and NF-κB p65, showing the basis for CA-induced synergistic inhibition. Our results provide valuable information for further studies.]] • Keywords: has publicationkeywords::NF-κB, has publicationkeywords::Apoptosis, has publicationkeywords::Cinnamaldehyde, has publicationkeywords::Inflammation, has publicationkeywords::Mesenteric ischemia/reperfusion injury, has publicationkeywords::Mitochondria, has publicationkeywords::Oxidative stress, has publicationkeywords::p53 • Bioblast editor: [[has editor::Plangger M]]

Labels: MiParea: MiP area::Respiration, MiP area::Pharmacology;toxicology 

Stress:Injury and adaptation::Ischemia-reperfusion  Organism: Organism::Rat  Tissue;cell: tissue and cell::Endothelial;epithelial;mesothelial cell  Preparation: Preparation::Permeabilized cells, Preparation::Intact cells 

Coupling state: Coupling states::LEAK, Coupling states::ROUTINE, Coupling states::OXPHOS, Coupling states::ET  Pathway: Pathways::N, Pathways::S, Pathways::NS, Pathways::ROX  HRR: Instrument and method::Oxygraph-2k