Model Experiment durations Herbal medicine Pathological and biochemical changes; mechanism involved Reference Hepatotoxins Thioacetamide induced 6 wks Kaerophyllin Reduced collagen accumulation and fibrosis score. Reduced ALT, AST, and α -SMA. Reduced TNFα , IL-1β , MCP-1, ICAM-1; increased PPAR-γ . [34 ] 7 wks Silybin Reduced Tbil, ALT, and AST levels and necrotic zones and steatosis. Reversed loss of CYP3A and PXR; reduced α -SMA and improved anti-inflammatory cytokines secretion. [103 ] 8 wks Ethanolic extract of rhizomes of Z. officinale [104 ] 8/12 wks Magnesium lithospermate B Reduced ALT, AST and α -SMA, TGF-β 1, and collagen-α 1 (I). Inhibited NF-κ B activation, MCP-1, and H2 O2 induced ROS production. [105 ] 12 wks Chunggan extract Reduced inflammation, collagen deposition, and large septa formation. Reduced ALP, AST and Bil, MDA, iNOS, and TNFα ; increased TGF-β . [106 ] DEN/DMN induced 3 wks Jia-wei-xiao-yao-san Reduced SOD, lipid peroxidation, and xanthine oxidase activity. [107 ] 4 wks Yinchenhao decoction (YCHD group) and Yiguanjian (YGJ group) Reduced Hyp and α -SMA. Reduced TNFα , PDGF, MDA, and GST activity; increased L-FABP and transferrin. [108 ] 4 wks Huangqi decoction Reduced hepatocyte apoptosis. Decreased apoptotic effectors, cleaved-caspase-3, α -SMA, and TGF-β 1. [109 ] 4 wks Yinchenhao decoction, Yinchen Wuling San, and Zhizi Baipi decoction Reduced Hyp content and Tbil level. [110 ] 4 wks Anluohuaxianwan Reduced ALT, AST, and contents of HA. Increased MMP-2. [111 ] 4 wks Huangqi decoction [112 ] 4 wks Fuzheng Huayu and Huangqi decoction [38 ] 4 wks Fuzheng Huayu recipe Reduced Hyp content. Reduced TGF-β 1, its receptor, and p-Smad2/3. [35 ] 4 wks Xiaopi pill Decreased ALT, AST, ALP and Tbil, and α -SMA. Reduced TGF-β 1, TIMP-1, and HO-1. [113 ] 4 wks Modified Sinisan Reduced liver injury biomarkers. [114 ] 4 wks Yi Guan Jian Reduced fibrotic septa, degenerated hepatocytes, and collagen deposition. Reduced collagen α 1-I, TIMP-1, and α -SMA. [115 ] 6 wks Vaccinium corymbosum L.Decreased liver apoptosis, necrosis, and proliferation. Reduced hepatic lipid peroxidation, protein oxidation, and nitrotyrosine levels; increased GST activity. [116 ] 6 wks Boswellia serrata and Salvia miltiorrhiza extractsShowed normal liver parenchymal architecture and only mild fibrosis.α -SMA, collagen I– collagen III, CTGF, TGF-β 1, Smad3, and Smad7. [117 ] 15 wks Gexiazhuyu decoction Decreased GOT and GPT. Reduced collagen α -1 and α -SMA. [118 ] Corbrin Shugan capsule [119 ] CCl4 4 wks Biejiayinzi, Gexiazhuyu Tang, and Fugan Wan Gexiazhuyu Tang and Fugan Wan treatment improved inflammatory necrosis and fat degeneration. Reduced collagen accumulation. [120 ] 6 wks Fuzhenghuayu decoction Decreased ALT, AST, and Tbil. Reduced area ratio of liver fibrosis and α -SMA. [37 ] 6 wks Xiayuxue decoction Decreased Sirius red positive area. Reduced α -SMA and type I collagen. [121 ] 6 wks Diwu Yanggan Reduced ALT, AST, Hyp, and collagen deposition and tissue damage. Increased E-cadherin, TGF-nc; reduced vimentin, BMP-7, Hh ligand Shh, receptor Smo and Ptc, and Gli1. [33 ] 6 wks Xuefuzhuyu decoction Reduced ALT, AST, Tbil, and Hyp. No ECM deposition and reduced necroinflammatory foci. Decreased α -SMA, collagen I, CD31, VEGF, VEGFR-2, HIF-1 alpha, and ADMA; increased DDAH1. [32 ] 7 wks Ethanol extract of Cortex Dictamni Improved pathological grading. Reduced collagen deposition and Hyp content. Increased pY-STAT1. [122 ] 8 wks Baicalin Decreased Hy, steatosis, liver necrosis, and fibrotic septa formation. Reduced TGF-β 1 and PPARγ . [123 ] 8 wks Coptidis rhizoma aqueous extractReduced Tbil and AST. Improved histological changes. Reduced SOD and Erk1/2 inhibition [40 ] 8 wks Cichorium intybus L. extractReduced ALT, AST, Hyp, and histopathological changes. Increased GSH, SOD; reduced MDA. Reduced TGF-β 1 and α -SMA. [124 ] 8 wks Fuzhenghuayu decoction Reduced ALT, AST, and hepatocyte apoptosis. Decreased collagen deposition and inflammatory cell infiltration. Reduced α -SMA and Hyp. [37 ] 8 wks Acremoniumterricola milleretal mycelium Decreased HA, laminin, and procollagen type III levels, Hyp. Improved pathological changes. Restored SOD and GSH-Px, inhibited lipid peroxidation. Decreased TGF-β , Smad2/3 phosphorylation and increased Smad7 inhibitor. [125 ] 8 wks Rougan Huaqian granules Decreased AST and HA. Reduced α -SMA, LN, Col I, Col III, Col IV, and MMP-2. [126 ] 8 wks Fufang Biejia Ruangan pills Decreased ALT, AST. Reduced collagen deposition and improved hepatic lesion. Reduced hyaluronic acid Col IV, type III procollagen laminin, TGF-β 1, and Smad3. [127 ] 8 wks Ganfukang Decreased ALT and AST. Ameriolated ductular proliferation. Reduced α -SMA, MMP-2 and TIMP-1, synthesis of collagen, and activation of the Wnt/beta-catenin. [128 ] 8 wks Huisheng oral solution Inhibited collagen formation and improved liver function. Reduced Smad3, TGF-β 1, α -SMA, and TIMP-1. [129 ] 8 wks Methanol extracts of Ficus carica Linn. (Moraceae) leaves and fruits and Morus alba Linn. root barks Reduced ALT, AST and ALP, and total bilirubin. Improved hepatocellular architecture. Restored antioxidant related content. [130 ] 9 wks Dahuangzhechong pill Decreased ALT, AST, HA, laminin, type IV collagen, and procollagen III and reverses hepatic fibrosis. Reduced α -SMA, serum TNF ASIL-13, p38MAPK, and Erk phosphorylation. [131 ] 9 wks Xiayuxue decoction Inhibited liver injury, fatty degeneration, and collagen deposition. Blocked CD31, vWF, VEGF, VEGFR2, DAF, α -SMA, and MMP-2 and MMP-9 activities. [132 ] 9 wks Yiguanjian decoction Increased Cu/Zn SOD, DJ-1, glutathione S-transferase Yb-1 subunit, and aldo-keto reductase family 7, A2. [133 ] 9 wks Yiguanjian Increased SOD, Prxd6, transferrin, and L-FABP; decreased MDA, HSP70, and HO-1. [67 ] 9 wks Yiguanjian decoction Reduced collagen deposition. Suppressed α -SMA, Col I, TIMP-1, TIMP-2, MMP-13, and MMP-14 and activities of MMP-2 and MMP-9. [68 ] 12 wks Huganjiexian decoction Inhibited collagen type I, collagen type III, TGF-β 1, and PDGF-BB. [134 ] 12 wks Xiaozheng Rongmu powder Changes in ALT, AST, and Tbil are milder and with hepatocytes mitosis. [135 ] 12 wks Shuganjianpifang Decreased steatosis, collagen accumulation, ALT, AST, and Tbil. Increased Alb. Reduced BAX and increased Bcl-2. [136 ] 13 wks Yiguanjian decoction Reduced ALT, α -SMA, and collagen deposition. Decreased F480, Alb, EGFP, PKM2, Ki-67, and AFP. [69 ] Others Ovariectomized rats 8 wks Citrus unshiu peel extractDecreased hepatic lipid contents, AST, and ALT. Reduced hepatic lipid deposition. [137 ] Porcine serum induced 16 wks Roots of Paeonia lactiflora and Astragalus membranaceus Reduced liver damage and symptoms of liver fibrosis. Decreased HA, PC III, and Hyp. Restored SOD and GSH and inhibited lipid peroxidation. [138 ] Schistosomiasis induced 18 wks Radix Astragali, Salvia miltiorrhiza , and Angelica sinensis Some groups showed small reticulation and spot thickening in liver. Reduced ALT, albumin, and TBil. [139 ] 18 wks Danggui Buxue decoction Reversed fibrosis. [140 ] Combination therapy CCl4 + high lipid low protein diet 6 wks Danggui Buxue decoction Reduced hepatic fatty degeneration and collagen accumulation. Decreased ALT, AST, and TBil. Reduced MDA, TG, Hyp content, and MMP-2/9 activities; increased SOD. [141 ] CCl4 , bile duct ligation, alcohol fed 7 wks Coptidis rhizoma extract and bear bileReduced AST, Hyp, and Tbil. Decreased hepatic damage and fibrosis. Reduced peroxidative stress; increased SOD. [41 ] CCl4 + high fat emulsion 8 wks flavonoids from Litsea coreana Levl Reduced ALT, AST, HA, laminin, procollagen III N-terminal peptide, procollagenase IV, and Hyp. Reduced hepatocyte degeneration, inflammatory cell infiltration, and collagen deposition. Suppressed α -SMA, collagen I, TGF-β 1, and its receptor; increased PPARγ . [142 ] DMN and CCl4 induced 8 wks (DMN) + 10 wks (CCl4 ) Graptopetalum paraguayense Reduced ALT, AST, and Tbil. Suppressed collagen deposition. [143 ]
