Andrographis paniculata as a Next-Generation Hepatoprotective Agent: An Updated Review on Andrographolide-Mediated Molecular Mechanisms and Translational Applications in Liver Disorders

Liver disorders represent a major global health burden, with oxidative stress, chronic inflammation, mitochondrial dysfunction, metabolic disturbances, and progressive fibrosis contributing to their pathogenesis. Andrographis paniculata, a medicinal plant widely used in traditional healthcare systems, has attracted considerable attention for its potential hepatoprotective properties, primarily attributed to its major bioactive diterpenoid lactone, andrographolide. This review critically examines the phytochemical profile, molecular mechanisms, experimental therapeutic applications, pharmacokinetic limitations, and translational prospects of A. paniculata in liver disorders. Preclinical investigations indicate that andrographolide may exert hepatoprotective effects through activation of Nrf2/Keap1/HO-1 antioxidant signaling, suppression of TLR4/NF-κB-mediated inflammation, modulation of MAPK and PI3K/Akt pathways, and inhibition of NLRP3 inflammasome activation. Additionally, regulation of AMPK-associated lipid metabolism, mitochondrial homeostasis, apoptosis, and TGF-β1/Smad-mediated fibrogenesis may contribute to its pharmacological activity. Experimental studies have demonstrated promising effects in models of metabolic dysfunction-associated steatotic liver disease, steatohepatitis, alcohol-associated liver injury, drug-induced hepatotoxicity, and hepatic fibrosis. However, poor aqueous solubility, variable oral bioavailability, limited target-specific validation, and insufficient clinical evidence remain important challenges. Emerging nanotechnology-based delivery systems, structural modifications, and liver-targeted formulations offer potential strategies for improving therapeutic performance. Future investigations should prioritize standardized preparations, comprehensive safety assessments, mechanistic validation, and well-designed clinical trials. Overall, A. paniculata and andrographolide represent promising candidates for hepatoprotective drug development, although their clinical efficacy and long-term safety require further investigation before therapeutic application can be established.