A standardized aqueous extract of Anoectochilus formosanus ameliorated thioacetamide-induced liver fibrosis in mice: the role of Kupffer cells.
Anoectochilus formosanus is used in traditional folk medicine as an hepatoprotective agent. The purpose of this study was to investigate the effects of a standardized aqueous extract of A. formosanus (SAEAF) on thioacetamide (TAA)-induced liver fibrosis. An in vitro study showed that the inhibitive effect of kinsenoside, a major component of SAEAF, on tumor necrosis factor alpha (TNF-alpha) secretion from Kupffer cells might be derived at least partly from downregulation of LPS-receptor Toll-like receptor 4 (TLR4) signaling. Hepatic fibrosis was produced by TAA (200 mg/kg, i.p.) 3 times per week for 12 weeks. Mice in the three TAA groups were treated daily with distilled water and SAEAF (1.0, 0.2 g/kg) via gastrogavage throughout the experimental period. The mice that received the SAEAF treatment had significantly reduced plasma alanine aminotransferase activity, relative liver weights, and hepatic hydroxyproline contents. A histological examination also confirmed that SAEAF reduced the degree of fibrosis caused by TAA treatment. RT-PCR analysis showed that SAEAF treatment reduced mRNA expression of collagen (alpha1)(I), lipopolysaccharide-binding protein, CD14, TLR4, and TNF receptor 1. An immunohistochemical examination also indicated that SAEAF reduced the number of CD68-positive cells (macrophages). In conclusion, oral administration of SAEAF significantly reduced TAA-induced hepatic fibrosis in mice, probably through inhibition of hepatic Kupffer cell activation.
Wu
Jin-Bin
JB
Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan.
Chuang
Hin-Ru
HR
Yang
Li-Chan
LC
Lin
Wen-Chuan
WC
D000209:Acute-Phase Proteins; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism / Q000494:pharmacology; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002352:Carrier Proteins; D015536:Down-Regulation / Q000187:drug effects; D006909:Hydroxyproline / Q000009:adverse effects / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008519:Medicine, Traditional; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013853:Thioacetamide / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein; D000097382:CD68 Molecule
D000209:Acute-Phase Proteins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002352:Carrier Proteins; D006909:Hydroxyproline; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D013853:Thioacetamide; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C495345:TLR4 protein, human