Isatidis Folium (IF) has been clinically combined with acetaminophen (APAP), but the rationality of combinational therapy is still ambiguous. In the present study, the protective effect and related mechanism of IF on APAP‐induced hepatotoxicity were evaluated. Hepatic histopathology and blood biochemistry investigations clearly demonstrated that IF could restore APAP‐induced hepatotoxicity. Liver distribution study indicated that the hepatoprotective effect of IF on APAP is attributed to the reduction of N‐acetyl‐p‐benzoquinone imine (NAPQI) in liver, which is a known hepatotoxic metabolite of APAP. Further study suggested the reduction is not via decreasing the generation of NAPQI through inhibiting the enzyme activities of CYP 1A2, 2E1, and 3A4 but via accelerating the transformation of NAPQI to NAPQI‐GSH by promoting GSH and decreasing GSSG contents in liver. Furthermore, IF significantly enhanced the hepatic activities of GSH‐associated enzymes in APAP‐treated mice. In summary, IF could alleviate APAP‐induced hepatotoxicity by reducing the content of NAPQI via enhancing the level of GSH and the followed generation of NAPQI‐GSH which might be ascribed to the upregulation of GSH‐associated enzymes.

中文翻译：

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板蓝根通过增强内源性抗氧化系统减轻对乙酰氨基酚引起的小鼠肝损伤

板蓝根（IF）已在临床上与对乙酰氨基酚（APAP）联合使用，但联合治疗的合理性尚不明确。在本研究中，评估了 IF 对 APAP 诱导的肝毒性的保护作用和相关机制。肝脏组织病理学和血液生化研究清楚地表明，IF 可以恢复 APAP 诱导的肝毒性。肝脏分布研究表明，IF 对 APAP 的保肝作用归因于肝脏中 N-乙酰基-对苯醌亚胺 (NAPQI) 的减少，这是一种已知的 APAP 肝毒性代谢物。进一步的研究表明，减少不是通过抑制 CYP 1A2、2E1 的酶活性来减少 NAPQI 的产生，和 3A4 但通过促进肝脏中 GSH 和降低 GSSG 含量来加速 NAPQI 向 NAPQI-GSH 的转化。此外，IF 显着增强了 APAP 治疗小鼠中 GSH 相关酶的肝脏活性。总之，IF 可以通过提高 GSH 水平和随后的 NAPQI-GSH 水平降低 NAPQI 含量来减轻 APAP 诱导的肝毒性，这可能归因于 GSH 相关酶的上调。