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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]