Treatment on Acute Liver Injury with Tian Jing Yi Xue Decoction by Repressing the PI3K/AKT/mTOR Signaling Pathway and Reducing Inflammation

Abstract

The increasing incidence of drug-induced acute liver injury (ALI) has drawn global attention to this health concern. Tian Jing Yi Xue Decoction (TJYXD), an ancient formula, has shown potential clinical efficacy for ALI. However, no studies have yet confirmed its effectiveness in treating ALI. In this study, we investigate the therapeutic potential of TJYXD in H2O2-induced HepG2 cell injury and CCl4-induced liver injury in Sprague-Dawley rats. High-performance liquid chromatography-mass spectrometry was used to analyze TJYXD components. Network pharmacology was employed to predict its mechanisms and effective components for ALI treatment, followed by experimental verification. In cellular experiments, 2 mg/mL TJYXD significantly reduced the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). In animal experiments, TJYXD significantly decreased the levels of ALT, ALP, and malondialdehyde and increased the level of superoxide dismutase. Histopathological analysis with Hematoxylin and Eosin staining and Masson staining further confirmed the efficacy of TJYXD compared to silymarin in treating ALI. Moreover, we determined that the therapeutic effects of TJYXD in the treatment of ALI were attributed to its inhibition of the PI3K/AKT/mTOR pathway and reduction in both serum and livers levels of transforming growth factor-β 1, interleukin-6, tumor necrosis factor-α. Furthermore, quercetin, apigenin, and luteolin were speculated to be the main active constituents. In conclusion, TJYXD demonstrates remarkable efficacy both in vitro and in vivo for the treatment of ALI by enhancing immunity and suppressing inflammation. Furthermore, TJYXD holds promise as a first-line or adjunctive therapeutic agent.