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Table 2 Pharmacological effects of natural products and herbal medicines with anti-liver fibrosis activity

From: Potent natural products and herbal medicines for treating liver fibrosis

Natural product/herbal medicine Pharmacological effect Model system References
Helioxanthin Inhibited HBV replication, suppressed IL-1-induced c-jun transcription and c-jun-mediated DNA binding activity of AP-1 HBV-producing HepG 2.2.15 cell line [44]
Wogonin Suppressed secretion of HBV antigens and reduced HBV DNA level through inhibition of HBV DNA polymerase activity HBV-producing MS-G2 cell line [46,47]
Matrine and oxymatrine Inhibited HBV surface antigen secretion, E antigen, and HBV DNA replication HBV-producing HepG 2.2.15 cell line [48,49]
Rhodiola kirilowii Maxim Inhibited HCV NS3 serine protease activity Cos-7(NS3/4A-SEAP) cell line [50]
Green tea Inhibited HCV viral entry and replication Primary human hepatocyte cells infected with HCV pseudoparticles, HCV-JFH1 viral culture system, patients with HCV infection and detectable viremia [51-53]
Glycyrrhizin acid Inhibited HCV full-length viral particle and HCV core gene expression syngenetically with IFNα, reduced hepatic inflammation, prevented apoptosis and inflammatory infiltrates HCV-infected liver cells, BALB/c mice [54-56]
Nobiletin Inhibited HCV absorption, reduced hepatic inflammation Human lymphoblastoid leukemia MOLT-4 cell line, and primary cultured rat hepatocytes [57,58]
Genistein Decreased levels of inflammation mediators, including IL-6, TNFα, and myeloperoxidase CCl4-induced rat hepatic fibrosis [61]
Salvianic acid A Inhibited proliferation of HSCs, reduced expression of TGF-β1 and collagen I/III HSC-T6 cell line [62]
Betulin, betulinic acid Inhibited expression of TNFα, TGF-β1, TIMP-1, TIMP-2, and MMP-2 Alcohol-induced liver fibrosis [63,64]
Gexia Zhuyu Tang Attenuated fibrogenesis and reduced inflammation, reduced CCl4-induced collagen deposition Late-stage liver fibrosis patients, CC4-induced mouse liver fibrosis [65,66]
Yanggan Wan Deactivated HSCs through epigenetic de-repression of PPAR-γ Bile duct-induced cholestatic mouse liver fibrosis [71]
Rosmarinic acid, baicalin De-repressed PPAR-γ through suppression of canonical Wnt signaling in activated HSCs Bile duct-induced cholestatic mouse liver fibrosis [71]
Yin Chen Hao Tang Decreased serum IFN-γ and IL-12 levels, inhibited α-SMA activation and transcription of its target genes Rat liver fibrosis model [75,76]
Paeoniflorin Reduced the size of egg granuloma, fibrosis scores, serum IL-13 levels, and hydroxyproline content, and blocked IL-13 signaling pathway CCl4-induced rat hepatic fibrosis [77,78]
Oleanolic acid, ursolic acid Inhibited bile acid production by blocking the interaction between FXR and its coactivator SRC-3 and endogenous ligand chenodeoxycholic acid, suppressed expression of FXR-targeted bile salt export protein, reduced hepatic free radicals through increasing hepatic transcription of Nrf2 target genes HepG2 cell line, wild-type and Nrf2-null mice [80-82]
Silymarin Protected liver from further damage through antioxidant and anti-inflammatory activity CCl4-induced rat liver fibrosis [84,85]
Silybinin Inhibited TGF-β1-induced collagen secretion and oxidase stress Thioacetamide-induced rat liver fibrosis [86]
Acanthus ilicifolius alkaloid A Reduced lipid peroxidation and oxidative stress CCl4-induced mouse liver fibrosis [87,88]
Curcumin Suppressed multiple proangiogenic factors that modulate cannabinoid receptors, inhibited ECM expression, decreased collagen deposition, increased serum MMP-13 and glutathione levels CCl4-induced rat liver fibrosis [89-91]
β-caryophyllene Exhibited high scavenging activity against hydroxyl radicals and superoxide anions, inhibited lipid peroxidation, suppressed expression of Col1a1 and TIMP-1 CCl4-induced mouse liver fibrosis [93]
Diwu Yanggan formula Modulated the EMT and MET balance CCl4-induced rat liver fibrosis [94]
Salvianolic acid B Abrogated EMT-induced fibrogenesis Renal fibrosis model [96]
Fuzheng Huayu tablet Reversed EMT in the fibrotic kidney through suppression of α-SMA, TGF-β1, and nuclear translocation of SMAD3; induced apoptosis through p38 and SAPK/JNK pathways; decreased transcription of TIMP-1, PDGF-B, and PDGF receptor β1; reversed HBV-induced fibrosis and cirrhosis; prevented TGF-β1-induced EMT Renal fibrosis model, HSC-T6 cells, patients with chronic hepatitis B, patients with cirrhosis caused by hepatitis B, renal fibrosis rats [95,97-105,122,123]
Fufang Biejia Ruangan pill Downregulated TGF-β1/SMAD pathway transduction Rats, HSC-T6 cell line, and clinical trial [45,49]
Silybin-phospholipids and vitamin E complex Reduced liver fibrosis scores and downregulated fibrosis markers, deactivated HSCs and downregulated TGF-β1 and TNFα Fatty liver-associated HCV-positive patients [109,110]
Obeticholic acid Inhibited synthesis and accumulation of bile acid in the liver, reduced liver inflammation and fibrosis Patients with type 2 diabetes and non-alcoholic fatty liver disease [111,112]
Docosahexaenoic acid Suppressed Procol1α1 and TGF-β1, inhibited hepatic inflammation and oxidative stress markers, including TLR4, TLR9, CD14, MyD88, and NADPH oxidase subunits Western diet-induced NASH in Ldlr(−/−) mice [114]