Human diet-derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization

Phytother Res. 2024 Jan;38(1):280-304. doi: 10.1002/ptr.8043. Epub 2023 Oct 23.

Abstract

This review focuses on the potential ameliorative effects of polyphenolic compounds derived from human diet on hepatic diseases. It discusses the molecular mechanisms and recent advancements in clinical applications. Edible polyphenols have been found to play a therapeutic role, particularly in liver injury, liver fibrosis, NAFLD/NASH, and HCC. In the regulation of liver injury, polyphenols exhibit anti-inflammatory and antioxidant effects, primarily targeting the TGF-β, NF-κB/TLR4, PI3K/AKT, and Nrf2/HO-1 signaling pathways. In the regulation of liver fibrosis, polyphenolic compounds effectively reverse the fibrotic process by inhibiting the activation of hepatic stellate cells (HSC). Furthermore, polyphenolic compounds show efficacy against NAFLD/NASH by inhibiting lipid oxidation and accumulation, mediated through the AMPK, SIRT, and PPARγ pathways. Moreover, several polyphenolic compounds exhibit anti-HCC activity by suppressing tumor cell proliferation and metastasis. This inhibition primarily involves blocking Akt and Wnt signaling, as well as inhibiting the epithelial-mesenchymal transition (EMT). Additionally, clinical trials and nutritional evidence support the notion that certain polyphenols can improve liver disease and associated metabolic disorders. However, further fundamental research and clinical trials are warranted to validate the efficacy of dietary polyphenols.

Keywords: NAFLD; hepatocellular carcinoma; liver fibrosis; polyphenolic compound.

Publication types

  • Review

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Diet
  • Humans
  • Liver / metabolism
  • Liver Cirrhosis / drug therapy
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Non-alcoholic Fatty Liver Disease* / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Wnt Signaling Pathway

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases