Kehuang capsule inhibits MAPK and AKT signaling pathways to mitigate CCl4-induced acute liver injury

作者：Qinyu Ni, Jiacheng Lin, Weifan Huang, Yang Liu, Ran Li, Tao Tu, G. X. He, Yueqiu Gao, Xuehua Sun, Xiaoni Kong, Xiaojun Zhu · 发表于：Liver Research · 年份：2024 · DOI：10.1016/j.livres.2024.11.006 · 被引用次数：5 · 研究领域：Drug-Induced Hepatotoxicity and Protection、Flavonoids in Medical Research、Traditional Chinese Medicine Analysis

Background and aims: )-induced acute liver injury (ALI) in a murine model. Methods: +KH_High group. Liver enzyme levels and histological changes were assessed to evaluate liver injury. Oxidative stress markers and inflammatory cell infiltration in liver tissues were measured. Additionally, network pharmacology was employed to explore the potential mechanisms of KH capsule. Results: KH capsule significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, as well as the necrotic area in liver tissue. KH capsule also decreased the infiltration of macrophages and neutrophils, thereby inhibiting the expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). Furthermore, KH capsule decreased liver malondialdehyde (MDA) levels and increased superoxide dismutase (SOD) activity. The number of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)-positive cells in liver tissue was also reduced. The expression of nuclear factor erythroid 2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins was significantly elevated, while the protein expression of cytochrome P450 2E1 (CYP2E1) was significantly reduced. Mass spectrometry identified genistein, galangin, wogonin, skullcapflavone II, and hispidulin as potential active ingredients of KH capsule. Network pharmacology analysis revealed enrichment in the mitogen-activated protein kinase (MAPK) and phosphatidylinositol...