Antifibrotic compounds from Liriodendron tulipifera attenuating HSC-T6 proliferation and TNF-α production in RAW264.7 cells.
The inhibition of hepatic stellate cell (HSC) proliferation has been considered as an effective therapeutic target for the treatment of liver fibrosis. The methanolic extract of Liriodendron tulipifera showed significant inhibitory activity against the proliferation of HSCs. Bioactivity-guided isolation afforded twelve compounds including (-)-sesamin (1), (-)-syringaresinol (2), (+)-dihydrodehydrodiconiferyl alcohol (3), salvinal (4), (+)-guaiacylglycerol-8-O-4'-dihydroconiferyl ether (5), (±)-guaiacylglycerol-8-O-4'-sinapyl alcohol ether (6), tanegool (7), (+)-5,5'-dimethoxy-7-oxolariciresinol (8), 3-hydroxy-4-methoxyacetophenone (9), 4-acetoxymethylphenol (10), (-)-paramicholide (11), and blumenol A (12). Among the compounds isolated, 2, 3 and 4 significantly attenuated the proliferation of the activated HSC-T6 cells. The maximal dose of these compounds, however, showed no cytotoxicity in primary cultured rat hepatocytes. Collagen deposition in the activated HSC-T6 cells was reduced by 2, 3 and 4. Also, the increased production of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α induced by lipopolysaccharide was decreased by 3 and 4 in RAW264.7 macrophage cells. Collectively, (-)-syringaresinol (2), (+)-dihydrodehydrodiconiferyl alcohol (3), and salvinal (4) isolated from L. tulipifera leaves and twigs exhibited selective antifibrotic activities toward the activated HSCs and suppressed TNF-α production in RAW264.7 macrophages. These compounds may be useful candidates for developing therapeutic agents for the prevention and treatment of hepatic fibrosis.
Department of Agronomy & Medicinal Plant Resources, College of Life Sciences and Natural Resources, Gyeongnam National University of Science and Technology.
Eun Ju
EJ
Jeong
Na-Hyun
NH
Kim
Jeong-Doo
JD
Heo
Ki Yong
KY
Lee
Jung-Rae
JR
Rho
Young Choong
YC
Kim
Sang Hyun
SH
Sung
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects; D008070:Lipopolysaccharides; D031567:Liriodendron; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D018547:Plant Stems; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D008070:Lipopolysaccharides; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen