The incidence of drug-induced liver injury (DILI) is second only to viral hepatitis and steatohepatitis in China, and DILI has become a serious public health problem that cannot be ignored. Guri Gumu-13 pill (GRGM) is a traditional Chinese medicine (TCM), which has a protective effect on liver diseases. However, the underlying therapeutic mechanisms of GRGM for DILI are still vague. In this study, the protective effect of GRGM on acetaminophen (APAP)-induced DILI was investigated based on the proteomics clues. The effects of GRGM on APAP-induced DILI in rats were studied using tandem mass tag (TMT)-based quantitative proteomics technology. Besides, western blotting was exerted to verify related proteins. Using the TMT-based quantitative proteomics approach, 237 proteins were identified as regulated in APAP-induced DILI and 58 proteins were regulated by GRGM. The 17 overlapping differentially expressed proteins (DEPs) were identified, and 7 proteins were inversely regulated. Enrichment analysis of KEGG indicated that metabolic pathways, linoleic acid metabolism, and retinol metabolism might be affected in DILI. Next, Cyp2c11, Aldh1a1, and Fads2 were verified with molecular biotechnology. GRGM exerts therapeutic effects through multi-pathways regulation in the treatment of DILI. This work may provide proteomics clues for the continuation of research on DILI treatment with GRGM.

药物性肝损伤（DILI）的发病率在我国仅次于病毒性肝炎和脂肪性肝炎，已成为不容忽视的严重公共卫生问题。固日固目13丸（GRGM）是一种中药（TCM），对肝脏疾病有保护作用。然而，GRGM 治疗 DILI 的潜在治疗机制仍不清楚。本研究基于蛋白质组学线索研究了 GRGM 对对乙酰氨基酚 (APAP) 诱导的 DILI 的保护作用。使用基于串联质量标签 (TMT) 的定量蛋白质组学技术研究了 GRGM 对 APAP 诱导的大鼠 DILI 的影响。此外，还应用了蛋白质印迹来验证相关蛋白质。使用基于 TMT 的定量蛋白质组学方法，237 种蛋白质被鉴定为在 APAP 诱导的 DILI 中受到调节，58 种蛋白质受到 GRGM 的调节。鉴定了 17 种重叠的差异表达蛋白 (DEP)，其中 7 种蛋白被反向调节。KEGG富集分析表明代谢途径、亚油酸代谢和视黄醇代谢可能在DILI中受到影响。接下来，用分子生物技术验证了 Cyp2c11、Aldh1a1 和 Fads2。GRGM在DILI治疗中通过多途径调控发挥治疗作用。这项工作可能为继续研究 GRGM 治疗 DILI 提供蛋白质组学线索。DILI 可能会影响视黄醇代谢。接下来，用分子生物技术验证了 Cyp2c11、Aldh1a1 和 Fads2。GRGM在DILI治疗中通过多途径调控发挥治疗作用。这项工作可能为继续研究 GRGM 治疗 DILI 提供蛋白质组学线索。DILI 可能会影响视黄醇代谢。接下来，用分子生物技术验证了 Cyp2c11、Aldh1a1 和 Fads2。GRGM在DILI治疗中通过多途径调控发挥治疗作用。这项工作可能为继续研究 GRGM 治疗 DILI 提供蛋白质组学线索。