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. 2023 Aug 2;8(6):e10579. doi: 10.1002/btm2.10579

TABLE 3.

Targets and new therapeutic strategies for hepatic fibrosis.

Targets MoA Therapeutics Modality Delivery systems References
Molecular level Gene Silenced the HMGB1 gene HMGB1‐siRNA siRNA NAL nanoparticles 73
Regulation of pro‐fibrotic genes in HSCs miRNA‐29b, miRNA‐122 miRNA Micelle 74
Noncoding RNAs Knockdown of miR‐221‐3p TuD‐miR‐221‐3p miRNA AAV8 76
Dysregulated miR‐34a Pterostilbene Small‐molecule N 78
Increased circRNA SCAR expression located in the mitochondria CircRNA SCAR expression vectors pcD‐ciR Mitochondria‐targeting NPs 84
Signaling pathway Inhibited TGF‐β1/Smad3 signaling Umbelliferone Small‐molecule N 85
Inhibited hedgehog signaling Vismodegib Small‐molecule cRGDyK‐liposome 87
Inhibited TGF‐β signaling TGF‐βR blocker Protein Lactococcus lactis 88
Cellular level Hepatocyte Hepatocyte protection Betulinic acid Small‐molecule Chitosan NPs 93
Improved fibrotic primary hepatocyte functions HNF4A mRNA mRNA Lipid NPs 94
HSCs Inhibited HSC activation Imatinib Small‐molecule Liposomes 96
HSC cytotoxicity activated GMO, miR‐29b Small‐molecule, miRNA PEG‐PLGA NPs 97
Inhibited HSC proliferation and activation Quercetin Small‐molecule Nanocages 98
Transformed aHSCs to quiescent phenotype Relaxin‐plasmid, miR‐30a‐5p mimic Gene, miRNA LPH NPs 99
Destroyed the Golgi structure and downregulated collagen I production Retinoic acid, DOX Small‐molecule Micelles 100
Broke down the dense collagen stroma and inhibited aHSC Collagenase, silibinin Enzyme, small‐molecule NPs 101
Thermal ablation Gold Inorganic material Nanorods 102
Hepatic immune cells Macrophage repolarized toward an anti‐fibrotic M1 phenotype CSF‐1R siRNA siRNA Nanohydrogel 104
Modulated M2 macrophages TSG‐6 Cytokine CaP@BSA NPs 105
Tissue level Reduced ROS levels PD‐MC Material Micelle 107
Reduced MMP‐9 mRNA expression MMP‐9 siRNA siRNA Vitamin A‐liposome 108

Abbreviations: GMO, Germacrone; HMGB1, human high mobility group box‐1; HNF4A, hepatocyte nuclear factor 4 alpha; MMP, matrix metalloproteinase; MoA, mechanism of action.