Matrine in Liver Diseases: Mechanistic Insights and Therapeutic Potential

Abstract: Matrine (C 15 H 24 N 2 O), a quinolizidine alkaloid abundant in Sophora flavescens and other legumes, has attracted considerable attention in recent years due to its remarkable pharmacological effects against a range of liver diseases. Extensive research has demonstrated that matrine exhibits significant therapeutic potential in the prevention and treatment of various liver disorders, including liver injury of diverse etiologies, metabolic-associated fatty liver disease, liver fibrosis and hepatocellular carcinoma. This review integrates recent literature from CNKI, Web of Science, ScienceDirect and PubMed to summarize advances in the application of matrine for liver disease therapy. According to current data, the hepatoprotective effects of matrine involve multiple molecular mechanisms, such as inhibition of inflammatory responses, reduction of oxidative stress, alleviation of endoplasmic reticulum stress, improvement of insulin resistance, mitigation of lipid peroxidation, as well as suppression of hepatocellular carcinoma cell proliferation, invasion, and migration through induction of autophagy and apoptosis. Notably, several signaling pathways, including NF-κB, Nrf2, HSF1/PGC-1α, PI3K/AKT/mTOR, JAK2/STAT3, RhoA/ROCK and Mst1-JNK, have been identified as critical mediators of its hepatoprotective actions. Toxicological data indicate that excessive doses or prolonged exposure to matrine may induce multisystem toxicity, affecting the liver, kidneys, nervous system and gastrointestinal tract. Pharmacokinetic studies reveal that matrine undergoes rapid absorption, exhibits moderate oral bioavailability and is subject to relatively rapid metabolic clearance. Additionally, this review outlines the natural sources, physicochemical properties and current research challenges associated with matrine, aiming to provide a solid theoretical foundation and clinical translation in the treatment of liver diseases. Keywords: liver diseases, matrine, hepatoprotection, mechanisms, toxicity, pharmacokinetics