Dioscin in liver diseases: pharmacological mechanisms, translational potential and future perspectives

Abstract

Dioscin (C45H72O16, DIO) is a naturally occurring steroidal saponin widely distributed in medicinal plants of the Dioscoreaceae, Liliaceae, and Fabaceae families. Given its remarkable hepatoprotective properties, DIO has attracted increasing attention in recent years. Based on literature retrieved from Web of Science, PubMed, ScienceDirect, and CNKI, this review systematically summarizes the pharmacological activities, molecular mechanisms, toxicological characteristics, and pharmacokinetic properties of DIO in liver diseases. Available evidence demonstrates that DIO exhibits significant therapeutic potential against various liver disorders, including liver injury, metabolic dysfunction-associated steatotic liver disease, cholestatic liver disease, liver fibrosis, and hepatocellular carcinoma. Mechanistically, DIO exerts hepatoprotective effects by regulating oxidative stress, inflammation, lipid metabolism, bile acid homeostasis, apoptosis, autophagy, and ferroptosis through multiple signaling pathways, including Keap1/Nrf2, TGF-β1/Smad, PI3K/Akt/mTOR, Wnt/β-catenin, TLR4/MyD88/NF-κB, and SLC7A11/GPX4. Toxicological studies indicate that DIO is generally well tolerated at therapeutic doses, whereas prolonged exposure or high-dose administration may induce hepatotoxicity, mild hematological toxicity, and gastrointestinal toxicity. Pharmacokinetic investigations reveal that DIO displays slow absorption, extremely low oral bioavailability, and prolonged intestinal retention. After absorption, it is distributed mainly to the liver and lungs, and undergoes deglycosylation, oxidation, and glucuronidation, with fecal excretion serving as the primary elimination route. In addition, this review covers the botanical sources, biological characteristics, novel drug delivery systems, and current research challenges associated with DIO. Overall, it provides a comprehensive basis for the further development and clinical translation of DIO in the prevention and treatment of liver diseases.