* Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
† College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Am J Chin Med. 2017;45(1):105-121. doi: 10.1142/S0192415X17500082. Epub 2017 Jan 13.
Acetaminophen (APAP) overdose causes hepatocytes necrosis and acute liver failure. Baicalin (BA), a major flavonoid of Scutellariae radix, has potent hepatoprotective properties in traditional medicine. In the present study, we investigated the protective effects of BA on a APAP-induced liver injury in a mouse model. The mice received an intraperitoneal hepatotoxic dose of APAP (300[Formula: see text]mg/kg) and after 30[Formula: see text]min, were treated with BA at concentrations of 0, 15, 30, or 60[Formula: see text]mg/kg. After 16[Formula: see text]h of treatment, the mice were sacrificed for further analysis. APAP administration significantly elevated the serum alanine transferase (ALT) enzyme levels and hepatic myeloperoxidase (MPO) activity when compared with control animals. Baicalin treatment significantly attenuated the elevation of liver ALT levels, as well as hepatic MPO activity in a dose- dependent manner (15-60[Formula: see text]mg/kg) in APAP-treated mice. The strongest beneficial effects of BA were seen at a dose of 30[Formula: see text]mg/kg. BA treatment at 30[Formula: see text]mg/kg after APAP overdose reduced elevated hepatic cytokine (TNF-[Formula: see text] and IL-6) levels, and macrophage recruitment around the area of hepatotoxicity in immunohistochemical staining. Significantly, BA treatment can also decrease hepatic phosphorylated extracellular signal-regulated kinase (ERK) expression, which is induced by APAP overdose. Our data suggests that baicalin treatment can effectively attenuate APAP-induced liver injury by down-regulating the ERK signaling pathway and its downstream effectors of inflammatory responses. These results support that baicalin is a potential hepatoprotective agent.
对乙酰氨基酚（APAP）过量会导致肝细胞坏死和急性肝功能衰竭。黄芩苷（BA）是黄芩根的主要黄酮类化合物，在传统医学中具有很强的保肝作用。在本研究中，我们研究了 BA 对 APAP 诱导的小鼠模型肝损伤的保护作用。小鼠接受了腹腔内肝毒性剂量的 APAP（300[Formula: see text]mg/kg），30[Formula: see text]min 后，用 0、15、30 或 60[Formula: see text]mg/kg 的 BA 进行治疗。治疗 16[Formula: see text]h 后，处死小鼠进行进一步分析。与对照组相比，APAP 给药显著升高了血清丙氨酸转移酶（ALT）酶水平和肝髓过氧化物酶（MPO）活性。黄芩苷治疗显著减弱了 APAP 处理小鼠中肝 ALT 水平以及肝 MPO 活性的升高，呈剂量依赖性（15-60[Formula: see text]mg/kg）。BA 的最佳有益作用出现在 30[Formula: see text]mg/kg 的剂量。APAP 过量后，BA 治疗 30[Formula: see text]mg/kg 可降低升高的肝细胞因子（TNF-[Formula: see text]和 IL-6）水平，并减少免疫组织化学染色中肝毒性区域周围的巨噬细胞募集。重要的是，BA 治疗还可以降低 APAP 过量诱导的肝磷酸化细胞外信号调节激酶（ERK）表达。我们的数据表明，BA 治疗可以通过下调 ERK 信号通路及其下游炎症反应效应物，有效减轻 APAP 诱导的肝损伤。这些结果支持 BA 是一种有潜力的保肝剂。
