Almoiliqy 2020 Acta Pharmacol Sin

From Bioblast
Publications in the MiPMap
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-ΞΊB and p53. Acta Pharmacol Sin 41:1208-22.

Β» PMID: 32238887

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) Acta Pharmacol Sin

Abstract: Our preliminary study shows that cinnamaldehyde (CA) could protect against intestinal ischemia/reperfusion (I/R) injuries, in which p53 and NF-ΞΊB 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-Ξ±, IL-1Ξ², 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-ΞΊB p65, IKKΞ², IK-Ξ±, and NF-ΞΊB 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-ΞΊB 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-ΞΊB p65 in H/R-treated IEC-6 cells. Double knockdown or overexpression of p53 and NF-ΞΊB p65 caused a synergistic reduction or elevation of p53 compared with knockdown or overexpression of p53 or NF-ΞΊB p65 alone. In H/R-treated IEC-6 cells with double knockdown or overexpression of NF-ΞΊB p65 and p53, CA pretreatment caused neither further decrease nor increase of NF-ΞΊB p65 or p53 expression, suggesting that CA-induced synergistic inhibition on both NF-ΞΊB 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-ΞΊB p65, showing the basis for CA-induced synergistic inhibition. Our results provide valuable information for further studies. β€’ Keywords: NF-ΞΊB, Apoptosis, Cinnamaldehyde, Inflammation, Mesenteric ischemia/reperfusion injury, Mitochondria, Oxidative stress, p53 β€’ Bioblast editor: Plangger M

Labels: MiParea: Respiration, Pharmacology;toxicology 

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

Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 


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