Phytochemical basis, multitarget pharmacology, and translational perspectives of silymarin: emphasis on its antifibrotic effects
Year: 2026
Type: article
Abstract: This review critically evaluates the antifibrotic potential of silymarin by integrating its phytochemical composition, formulation-dependent exposure, molecular pharmacology, cross-organ preclinical evidence, and clinical translation, while distinguishing multicomponent silymarin extracts from purified silybin/silibinin and delivery-enhanced preparations. A structured, non-systematic evidence-mapping search of PubMed/MEDLINE, Web of Science, and Scopus covered English-language literature through December 2025. A targeted update of PubMed/MEDLINE and publisher records was performed through 9 August 2026, focusing on fibrosis, pharmacokinetics, formulation, drug delivery, ferroptosis, succinate metabolism, ANXA6, and related mechanisms. Preclinical studies indicate that silymarin-related interventions can modulate TGF-β/Smad signaling, oxidative and inflammatory pathways, fibroblast activation, myofibroblast differentiation, and extracellular-matrix turnover. Recent work has added hepatocyte succinate handling, FTH1-related ferroptosis, and ANXA6-associated stress signaling. Antifibrotic activity has been reported in liver, kidney, lung, peritoneal, and skin models, whereas human evidence remains limited and heterogeneous. Product composition, oral exposure, formulation, and endpoint selection may contribute to discordant clinical findings. Silymarin has biologically plausible multitarget antifibrotic activity, but current evidence does not establish it as an antifibrotic therapy. Future studies should use chemically defined preparations, exposure-informed dosing, validated target engagement, and fibrosis-centered outcomes.
Source: Frontiers in Pharmacology
Authors: Zhe Jin, Jing Zhu, Binghong Lu, Yabo Li, Yan Chen
Institution: Yangzhou University
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223303046