Abstract：
Excess acetaminophen (APAP) commonly causes severe acute liver injury (ALI), characterized by oxidative stress, pro-inflammatory responses, and hepatocyte damage. Veronica persica (VP) is a traditional medicine with antioxidant and anti-inflammatory properties. There is a paucity of information on its medicinal value, especially its potential mechanisms for alleviating ALI. This study aimed to clarify the ameliorative effects and intracellular mechanisms of VP on APAP-induced ALI via attenuating oxidative stress and inflammation. Mice were given VP for 7 days before exposure to APAP (300 mg/kg). The HPLC and radical scavenging assay found that VP contains 12 phenolic acids and 6 flavonoids, as well as show robust antioxidant capacity. In the APAP-induced ALI model, pre-treatment with VP significantly reduces APAP-induced hepatotoxicity by observing improved hepatocyte pathological injury and further confirmed by serum biochemical indicator. Also, the reduction of TUNEL-positive regions and the regulation of Bcl-2-associated X protein indicated that VP attenuates hepatocytotoxicity. Moreover, VP pre-intervention inhibits the formation of liver pro-inflammatory cytokines, the expression of inflammatory response genes, and increases in myeloperoxidase (MPO) in APAP-exposed mice. The elevated reduced glutathione (GSH) levels and decreased oxidative stress markers indicate that VP reduces APAP-promoted oxidative stress. Further study revealed that VP inhibited the phosphorylation of NF-κB/STAT3 cascade, blocked ERK and JNK phosphorylation, and activated AMP-activated protein kinase (AMPK). To sum up, this study demonstrated that VP exists hepatoprotective abilities on APAP-induced ALI, primarily by suppressing the phosphorylation of NF-κB/STAT3 cascade and ERK-JNK and inducing AMPK activation to alleviate oxidative stress and inflammation.
摘要：
过量的对乙酰氨基酚（APAP）通常会导致严重的急性肝损伤（ALI），以氧化应激为特征，促炎反应，和肝细胞损伤。维罗妮卡（VP）是一种具有抗氧化和抗炎特性的传统医学。关于其药用价值的信息很少，尤其是其缓解ALI的潜在机制。本研究旨在阐明VP通过减轻氧化应激和炎症对APAP诱导的ALI的改善作用及其细胞内机制。在暴露于APAP(300mg/kg)之前,给予小鼠VP7天。HPLC和自由基清除实验发现，VP含有12种酚酸和6种黄酮类化合物，并显示出强大的抗氧化能力。在APAP诱导的ALI模型中，VP预处理可显著降低APAP诱导的肝毒性，观察肝细胞病理损伤的改善，并通过血清生化指标进一步证实。此外，TUNEL阳性区域的减少和Bcl-2相关X蛋白的调节表明VP减弱肝细胞毒性。此外，VP预干预抑制肝脏促炎细胞因子的形成，炎症反应基因的表达，暴露于APAP的小鼠中髓过氧化物酶（MPO）的增加。升高的还原型谷胱甘肽(GSH)水平和降低的氧化应激标志物表明VP降低了APAP促进的氧化应激。进一步研究发现VP抑制NF-κB/STAT3级联的磷酸化,阻断ERK和JNK磷酸化，和激活的AMP激活的蛋白激酶(AMPK)。总而言之,这项研究表明，VP对APAP诱导的ALI存在保肝能力，主要通过抑制NF-κB/STAT3级联和ERK-JNK的磷酸化和诱导AMPK活化来减轻氧化应激和炎症反应。
