Table 2.
Chinese medicine and their derivatives equipped with antifibrotic property.
| Drugs | Categories | Mechanisms | Signaling pathways | Phenotypes | Cells or animal models | Reference |
|---|---|---|---|---|---|---|
| Chloroquine | Monomer | LC3-II protein accumulation | Stemness, invasion, and metastasis ↓ of CAF-CM-treated Huh7 | CAFs | (150) | |
| Curcumin | Herbal extract | CTGF suppression | NF-κB and ERK | Type I collagen ↓ in HSC | Primary HSCs | (155) |
| PPARγ stimulation | PPARγ-ROS; PDGF and EGF signaling | Oxidative stress, inflammation ↓; α-SMA and collagen I ↓ in HSC; serum AST, ALT, and ALP ↓; liver histological architecture improved | CCl4-induced liver fibrotic rats; primary HSCs | (156–159) | ||
| α-Lipoic acid; N-acetylcysteine | Monomer | Oxidative stress reduction and MMP13 induction | TGF-α signaling | Collagen deposition ↓; serum AST, ALT, and γ-GT ↓; GSH ↑ | CCl4-induced liver fibrotic rats | (156) |
| Magnesium isoglycyrrhizinate | Herbal extract | Heme oxygenase-1 stimulation | Heme oxygenase-1/ferrostatin-1 | Fibrotic scar formation ↓; ferroptosis-related cell death of HSC | CCl4-induced liver fibrotic rats | (147) |
| Artemether | Monomer | Tumor-suppressor p53 stimulation | Liver injury and fibrotic scar formation ↓; ferroptosis-related cell death of HSC | CCl4-induced liver fibrotic mice; primary HSCs | (148) | |
| IRP2 accumulation | IRP2–iron–ROS axis | Production of iron and ROS ↑ in HSC; ferroptosis-related cell death of HSC | Activated LX2 | (149) | ||
| Osthole | Monomer | Nuclear translocation of p65 suppression; oxidative stress reduction and inflammation inhibition | TGF-β1/NF-κB | Plasma AST and ALT ↓; histological architecture and hepatic fibrosis scores improved; collagen and α-SMA ↓ | Thioacetamide-induced liver fibrotic rats; activated HSC-T6 and LX2 | (160) |
| Ginkgo biloba extract | Herbal extract | Oxidative stress reduction; NF-κB p65 suppression | TGF-β1/NF-κB | Serum ALT, AST, HA, and LN ↓; histopathologic scores of liver fibrosis ↓; collagen I and α-SMA ↓ | CCl4-induced liver fibrotic rats; primary HSCs | (161, 162) |
| 18α-Glycyrrhizin; glycyrrhetinic acid; glycyrrhizin | Monomer | Blockade of the translocation of NF-κB | NF-κB | α-SMA ↓ in HSC; HSC apoptosis; procollagen I and III ↓ | CCl4-induced liver fibrotic rats; primary HSCs | (163, 164) |
| NLRP3 inhibition; inflammation-mediated hepatic farnesoid X receptor inhibition; restoration of bile acid homeostasis | Hepatic steatosis, inflammation, and fibrosis improved; serum bile acid accumulation ↓ | Methionine- and choline-deficient diet-induced NASH mice model | (153) | |||
| Baicalin | Monomer | TGF-β1 suppression; PPARγ stimulation | HSC activation ↓ | CCl4-induced liver fibrotic rats | (145) | |
| Silymarin | Monomer | CTGF and hepatic hydroxyproline decrease; SOD and GPx increase | Plasma AST and ALT ↓; hepatic fibrosis formation ↓ | CCl4-induced liver fibrotic rats | (165) | |
| Boswellia serrata and Salvia miltiorrhiza combination | Herbal extract | CTGF, TGF-β1, Smad3, and Smad7 reduction | TGF-β signaling | Histological severity of fibrosis improved; α-SMA ↓; collagen I, II, and III ↓ | DMN-induced liver fibrotic rats | (166) |
| Sedum sarmentosum total flavanones | Herbal extract | Smad2/3, Smad4 decrease; Smad7 increase | Smads pathway | Serum ALT, AST, HA, and LN ↓; α-SMA ↓ | CCl4-induced liver fibrotic rats | (133) |
| Methyl ferulic acid | Monomer | TGF-β1/Smad and NOX4/ROS | HSC proliferation ↓; α-SMA and collagen I ↓ | Activated LX2 | (47) | |
| Praziquantel | Monomer | Smad7 increase | TGF-β/Smad signaling | Activation of HSC ↓; collagen matrix ↓ | CCl4-induced liver fibrotic mice; activated HSC-LX2, fibroblast-like cell line MES13, and fibroblast cell line NIH3T3 | (167) |
| Conophylline | Alkaloid | G protein-coupled receptor 68 suppression | α-SMA ↓ in CAFs; cancer-promoting effects of CAFs ↓; cytokines including IL-6, IL-8, CXCL2, angiogenin, and OPN ↓ produced by CAFs | Primary CAFs | (52) | |
| Coptisine | Alkaloid | Blocked secretion of CAF-derived exosomal circCCT3; changed glucose metabolism in HCC cells | circCCT3/HK2 | Cell viability and metastasis ↓ of CAF-CM-treated Huh7 and HepG2 | Primary CAFs; clinical HCC tumors | (151, 152) |
| Salvianolic acid A | Monomer | Apoptosis of HSC | PI3K/AKT/mTOR; Bcl-2/Bax; caspase-3/cleaved caspase-3 | Liver fibrosis index ↓; collagen deposition ↓; activation of HSC ↓; synthesis of extracellular matrix ↓ | CCl4-induced liver fibrotic rats; primary CAFs | (134) |
| Xiaoyaosan | Decoction | p-FoxO3a, p-Smad3, and p-Akt decrease | TGF-β/Smad and Akt/FoxO3 | Liver function improved; fibrotic changes alleviated; α-SMA and collagen I ↓ | CCl4-induced liver fibrotic rats; activated LX2 | (135) |
| Yinchenhao decoction | Decoction | Cleaved caspase-3 decrease in L02 cells; p-ERK1/2, PI3K, and Bcl-XL protein increase in L02 cells; Bax and cleaved caspase-8 increase in LX2 cells | Apoptosis-related signaling | Liver fibrosis improved; apoptosis of hepatic parenchyma cells ↓; LX2 cell proliferation ↓ | DMN-induced liver fibrotic rats; human hepatic L02 cells and activated LX2 cells | (136) |
| Phillygenin | Monomer | TLR4, MyD88, IKKβ, p65, IκBα, and TAK1 molecular docking | TLR4/MyD88/NF-κB | Collagen I and α-SMA ↓ in LX2; IL-6, IL-1β, and TNF-α ↓ in LX2 | Activated LX2 cells | (154) |
| Forsythiae fructus | Herbal extract | TLR4/MyD88/NF-κB and TGF-β/Smads signaling | Hepatic histopathological injury, abnormal liver function, fibrosis, and inflammation improved; α-SMA and collagen-1 ↓ | CCl4-induced liver fibrotic rats | (168) |
CAF, cancer-associated fibroblasts; CM, conditioned medium; CTGF, connective tissue growth factor; NF-κB, nuclear factor-κB; HSC, hepatic stellate cell; PPARγ, peroxisome proliferator-activated receptor γ ; ROS, reactive oxygen species; PDGF, platelet-derived growth factor; EGF, epidermal growth factor; α-SMA, α-smooth muscle actin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; CCL4, carbon tetrachloride; MMP, matrix metalloproteinase; TGF, transforming growth factor; γ-GT, γ-glutamyl transferase; GSH, L-glutathione; IRP2, iron regulatory protein 2; HA, hyaluronic acid; LN, laminin; NLRP3, nucleotide-binding and oligomerization domain-like receptor containing pyrin domain containing 3; NASH, non-alcoholic steatohepatitis; SOD, superoxide dismutase; DMN, N-nitrosodimethylamine; Bcl-2, B-cell lymphoma-2; Bax, BCL2-associated X; IL, interleukin; TNF, tumor necrosis factor; TLR, Toll-like receptors. ↑：upregulation, ↓：downregulation.