6-姜辣素,生姜的主要生物活性化合物,有抗氧化剂,抗炎,抗癌和神经保护作用。然而,目前尚不清楚6-姜酚是否对肝脏缺血/再灌注(I/R)损伤具有保护作用。在这项研究中,采用不同浓度的6-姜酚预处理建立小鼠肝脏I/R损伤模型和小鼠AML12细胞缺氧/复氧(H/R)模型,探讨6-姜酚的潜在作用。血清转氨酶水平,肝坏死区,细胞活力,炎症反应,和细胞凋亡被用来评估6-姜酚对肝脏I/R或细胞H/R损伤的影响。定量聚合酶链反应(qPCR)和蛋白质印迹检测mRNA和蛋白质表达。结果表明,6-姜酚降低血清丙氨酸氨基转移酶(ALT),谷草转氨酶(AST)水平,肝坏死,炎症细胞因子IL-1β,IL-6、MCP-1、TNF-α表达,Ly6g+炎性细胞浸润,NF-κB信号通路的蛋白磷酸化,末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)阳性细胞,细胞凋亡率,促凋亡蛋白BAX和C-Caspase3的蛋白表达,增加细胞活力,和抗凋亡蛋白BCL-2的表达。此外,6-姜辣素可以增加丝裂原活化蛋白激酶磷酸酶5(MKP5)的mRNA和蛋白表达,抑制P38/JNK信号通路的激活。在MKP5敲除(KO)小鼠中,6-姜辣素的保护作用和对P38/JNK通路的抑制作用明显减弱。因此,我们的结果表明,6-姜酚通过调节MKP5介导的P38/JNK信号通路,发挥抗炎和抗凋亡作用,减轻肝脏I/R损伤.
6-Gingerol, the main bioactive compound of ginger, has antioxidant, anti-inflammatory, anti-cancer and neuroprotective effects. However, it is unclear whether 6-Gingerol has protective effects against hepatic ischemia/reperfusion (I/R) injury. In this study, the mouse liver I/R injury model and the mouse AML12 cell hypoxia/reoxygenation (H/R) model were established by pretreatment with 6-Gingerol at different concentrations to explore the potential effects of 6-Gingerol. Serum transaminase levels, liver necrotic area, cell viability, inflammatory response, and cell apoptosis were used to assess the effect of 6-Gingerol on hepatic I/R or cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to detect the mRNA and protein expression. The results show that 6-Gingerol decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, liver necrosis, inflammatory cytokines IL-1β, IL-6, MCP-1, TNF-α expression, Ly6g+ inflammatory cell infiltration, protein phosphorylation of NF-κB signaling pathway, Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) positive cells, cell apoptosis rate, the protein expression of pro-apoptotic protein BAX and C-Caspase3, increased cell viability, and expression of anti-apoptotic protein BCL-2. Moreover, 6-Gingerol could increase the mRNA and protein expression of mitogen activated protein kinase phosphatase 5 (
MKP5) and inhibit the activation of P38/JNK signaling pathway. In
MKP5 knockout (KO) mice, the protective effect of 6-gingerol and the inhibition of P38/JNK pathway were significantly weakened. Therefore, our results suggest that 6-Gingerol exerts anti-inflammatory and anti-apoptotic effects to attenuate hepatic I/R injury by regulating the
MKP5-mediated P38/JNK signaling pathway.