Hepatoprotective natural polyphenol extracts: molecular mechanisms, stabilization-delivery strategies, and translational bottlenecks for functional food applications
Year: 2026
Type: review
Abstract: Natural polyphenols exert multi-target hepatoprotective activities via orchestrating hepatic redox homeostasis, lipid metabolism, and hepatic innate-adaptive immune responses, yet their clinical and food-grade translation is hampered by poor stability, low bioavailability and dose-dependent safety risks. This review integrates polyphenol classification with critical toxicological analysis to address pro-oxidant, endocrine-disrupting, and immune-perturbing hazards under high-dose supplementation. We systematically construct multipathway hepatoprotective networks, highlighting polyphenol-driven immunomodulatory effects including macrophage polarization, NLRP3 inflammasome repression, and immunometabolic reprogramming, alongside classical antioxidant, anti-inflammatory, lipid-homeostasis-regulating, anti-pyroptotic, anti-apoptotic and antifibrotic outputs. Four stabilization-delivery approaches are assessed, alongside key bottlenecks including crude extract batch variation, incomplete recognition of gut-liver immune crosstalk, costly nanocarriers and deficient quantitative immune-phenotyping evaluation systems. An integrated strategy combining molecular modification, green stabilization, hepatocyte-/immune-cell-responsive delivery and therapeutic-efficacy traceability is proposed to advance polyphenol-based hepatoprotective candidates for immune-mediated liver injury.
Source: Frontiers in Immunology
Authors: Xiaoxiao Yao, Ruining Zhang, Yi Wang, Yi’en Xiang
Language: English
Subfield: Biochemistry (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223378335