Liver Disease and Plant-Derived Phytoconstituents: From Ethnopharmacology to Modern Medicine.

Liver diseases such as viral hepatitis, fatty liver disease, autoimmune and genetic disorders, drug-induced liver injury, hepatocellular carcinoma, and cirrhosis represent a major global health burden, while current pharmacotherapies remain limited by suboptimal efficacy, adverse effects, and poor accessibility. Ethnopharmacological use of medicinal plants offers a rich resource for discovering novel hepatoprotective agents, particularly secondary metabolites including alkaloids, flavonoids, terpenoids, glycosides, tannins, and saponins that target key pathogenic processes such as oxidative stress, inflammation, fibrosis, apoptosis, and metabolic dysregulation. This review systematically integrates traditional knowledge with modern evidence from in vitro, in vivo, preclinical, and clinical studies to highlight plant-derived phytoconstituents with demonstrated benefits across the spectrum of liver diseases, including clinically investigated agents such as silymarin, glycyrrhizin, curcumin, resveratrol, and ginsenosides. Mechanistic sections summarize disease progression from inflammation to fibrosis, cirrhosis, and hepatocellular carcinoma, and delineate how specific phytoconstituents modulate signaling pathways, redox homeostasis, lipid metabolism, and cell death programs, while pharmacokinetic data address absorption, distribution, metabolism, excretion, and strategies to overcome low oral bioavailability. The article also contrasts the limitations of current synthetic drugs with regulatory advances for botanical products across major agencies (FDA, EMA, WHO, and Asian regulators), and outlines methodological innovations including high-throughput screening, cheminformatics, in silico docking, organoid and liver-on-chip models, and nanotechnology-based delivery systems that can accelerate phytoconstituent-driven drug development. Overall, this review provides a comprehensive framework that links ethnomedicinal use, experimental validation, regulatory context, and technological progress, and identifies priority phytoconstituents and research directions for translating plant-based hepatoprotective agents into standardized, clinically effective therapies for liver disease.