Deciphering the Role of Oroxylin A in Liver Fibrosis

Liver fibrosis is a dynamic and complex process characterized by the excessive accumulation of extracellular matrix (ECM) components, driven by a heterogeneous population of hepatic myofibroblasts (MFs). Current treatments for liver fibrosis primarily include pharmacological interventions such as antiviral and anti-fibrotic therapies, alongside lifestyle modifications, including dietary changes and alcohol abstinence. However, the therapeutic outcomes remain suboptimal. Existing anti-fibrotic medications are unable to fully reverse liver fibrosis, particularly in its advanced stages, and some drugs may even induce adverse effects. Recently, the challenge of combating liver fibrosis has attracted increasing attention from both the academic community and the general public, leading to extensive research efforts and several significant discoveries. Hepatocyte senescence, an irreversible and inevitable process, plays a crucial role in the onset and progression of various liver diseases. It serves as a key regulatory factor in the development of liver fibrosis, exerting a considerable impact on its progression. Senescent hepatocytes secrete the senescence-associated secretory phenotype (SASP), which interacts with hepatic stellate cells (HSCs), promoting their transformation into MFs. Additionally, SASP fosters a cellular microenvironment conducive to the advancement of hepatic fibrosis, thereby accelerating its progression. This review comprehensively examines the natural flavonoid compound Oroxylin A (OA), which regulates hepatocyte senescence in the context of liver fibrosis. The paper also discusses the current research landscape, trends, and critical challenges related to hepatocyte senescence in liver fibrosis, along with the mechanisms through which OA influences hepatocyte senescence, either promoting or delaying its onset.