Cinnamaldehyde protects against rat intestinal ischemia/reperfusion injuries by synergistic inhibition of NF-κB and p53  

作　　者：Marwan Almoiliqy Jin Wen Bin Xu Yu-chao Sun Meng-qiao Lian Yan-li Li Eskandar Qaed Mahmoud Al-Azab Da-peng Chen Abdullah Shopit Li Wang Peng-yuan Sun Yuan Lin 

机构地区：[1]Pharmaceutical College,Dalian Medical University,Dalian,116044,China [2]Laboratory Animal Center,Dalian Medical University,Dalian,116044,China

出　　处：《Acta Pharmacologica Sinica》2020年第9期1208-1222,共15页中国药理学报（英文版）

基　　金：This study was supported by the National Natural Science Foundation of China(Grant No.30772601,81302838).

摘　　要：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 12.5μmol·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.Fina

关 键 词：CINNAMALDEHYDE mesenteric ischemia/reperfusion injury inflammation oxidative stress apoptosis MITOCHONDRIA P53 NF-ΚB 

分 类 号：R96[医药卫生—药理学]