Hepatoprotective natural polyphenol extracts: molecular mechanisms, stabilization-delivery strategies, and translational bottlenecks for functional food applications
- 1Jilin University Engineering Laboratory for Translational Medicine of Hepatobiliary and Pancreatic Diseases, The Second Norman Bethune Clinical Medical College of Jilin University
- 2College of Food Science and Engineering, Jilin Agricultural University
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.
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BibTeX
@article{yao2026hepatoprotective,
title = {{Hepatoprotective natural polyphenol extracts: molecular mechanisms, stabilization-delivery strategies, and translational bottlenecks for functional food applications}},
author = {Xiaoxiao Yao and Ruining Zhang and Yi Wang and Yi’en Xiang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1988758},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1988758/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hepatoprotective natural polyphenol extracts: molecular mechanisms, stabilization-delivery strategies, and translational bottlenecks for functional food applications
AU - Xiaoxiao Yao
AU - Ruining Zhang
AU - Yi Wang
AU - Yi’en Xiang
PY - 2026
DA - 2026/10/23
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1988758
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1988758/full
AB - 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.
SN - 1664-3224
ER -