- 作者: Ting-Chun Weng; Chien-Chang Shen; Yung-Tsung Chiu; Yun-Lian Lin; Cheng-Deng Kuo; Yi-Tsau Huang
- 作者服務機構: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
Activation of hepatic stellate cells (HSCs) plays a crucial role in liver fibrogenesis.
armepavine (Arm, C19H23O3N), an active compound from Nelumbo nucifera, has been
shown to exert immunosuppressive effects on T lymphocytes and on lupus nephritic mice.
The aim of this study was to investigate whether Arm could exert anti-hepatic fibrogenic
effects in vitro and in vivo. A cell line of rat HSCs (HSC-T6) was stimulated with tumor
necrosis factor-α (TNF-α) or lipopolysaccharide (LPS) to evaluate the inhibitory effects
of Arm. An in vivo therapeutic study was conducted in bile duct-ligated (BDL) rats. BDL
rats were given Arm (3 or 10 mg/kg) by gavage twice daily for 3 weeks starting from the
onset of BDL. Liver sections were taken for fibrosis scoring, immuno-fluorescence
staining and quantitative real-time mRNA measurements. In vitro, Arm (1-10 μM)
concentration-dependently attenuated TNF-α- and LPS-stimulated α-SMA protein
expression and AP-1 activation by HSC-T6 cells without adverse cytotoxicity. Arm also
suppressed TNF-α-induced collagen collagen deposition, NFκB activation and MAPK
(p38, ERK1/2, and JNK) phosphorylations. In vivo, Arm treatment significantly reduced
plasma AST and ALT levels, hepatic α-SMA expression and collagen contents, and
fibrosis scores of BDL rats as compared with vehicle treatment. Moreover, Arm
attenuated the mRNA expression levels of col 1α2, TGF-β1, TIMP-1, ICAM-1, iNOS, and
IL-6 genes, but up-regulated metallothionein genes. Our study results showed that Arm
exerted both in vitro and in vivo antifibrotic effects in rats, possibly through anti-NF-κB
activation pathways. - 中文關鍵字: --
- 英文關鍵字: --