■据报道,NepetoidinB(NB)具有抗炎作用,抗菌,和抗氧化性能。然而,其对肝脏缺血/再灌注(I/R)损伤的影响尚不清楚。
■在这项研究中,采用小鼠肝脏I/R损伤模型和小鼠AML12细胞缺氧复氧(H/R)损伤模型研究NB的潜在作用。血清转氨酶水平,肝坏死区,细胞活力,氧化应激,炎症反应,并对细胞凋亡进行评估,以评估NB对肝脏I/R和细胞H/R损伤的影响。定量聚合酶链反应(qPCR)和蛋白质印迹用于测量mRNA和蛋白质表达水平,分别。分子对接用于预测NB和丝裂原活化蛋白激酶磷酸酶5(MKP5)的结合能力。
■结果表明,NB显着降低了血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平,肝坏死,氧化应激,活性氧(ROS)含量,炎性细胞因子含量和表达,炎性细胞浸润,和肝I/R和AML12细胞H/R损伤后的凋亡。此外,NB抑制JUN蛋白氨基末端激酶(JNK)/P38通路。分子对接结果显示NB与MKP5蛋白结合良好,Westernblotting结果显示NB增加了MKP5的蛋白表达。MKP5敲除(KO)可显著降低NB对肝损伤的保护作用及其对JNK/P38通路的抑制作用。
■NB通过调节MKP5介导的P38/JNK信号通路对肝脏I/R损伤发挥保肝作用。
UNASSIGNED: Nepetoidin B (NB) has been reported to possess anti-inflammatory, antibacterial, and antioxidant properties. However, its effects on liver ischemia/reperfusion (I/R) injury remain unclear.
UNASSIGNED: In this study, a mouse liver I/R injury model and a mouse AML12 cell hypoxia reoxygenation (H/R) injury model were used to investigate the potential role of NB. Serum transaminase levels, liver necrotic area, cell viability, oxidative stress, inflammatory response, and apoptosis were evaluated to assess the effects of NB on liver I/R and cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to measure mRNA and protein expression levels, respectively. Molecular docking was used to predict the binding capacity of NB and mitogen-activated protein kinase phosphatase 5 (MKP5).
UNASSIGNED: The results showed that NB significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver necrosis, oxidative stress, reactive oxygen species (ROS) content, inflammatory cytokine content and expression, inflammatory cell infiltration, and apoptosis after liver I/R and AML12 cells H/R injury. Additionally, NB inhibited the JUN protein amino-terminal kinase (JNK)/P38 pathway. Molecular docking results showed good binding between NB and MKP5 proteins, and Western blotting results showed that NB increased the protein expression of MKP5. MKP5 knockout (KO) significantly diminished the protective effects of NB against liver injury and its inhibitory effects on the JNK/P38 pathway.
UNASSIGNED: NB exerts hepatoprotective effects against liver I/R injury by regulating the MKP5-mediated P38/JNK signaling pathway.