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2016 ; 14
(1
): 263
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Moniliformediquinone as a potential therapeutic agent, inactivation of hepatic
stellate cell and inhibition of liver fibrosis in vivo
#MMPMID27612633
Tseng TH
; Lin WL
; Chen ZH
; Lee YJ
; Shie MS
; Lee KF
; Shen CH
; Kuo HC
J Transl Med
2016[Sep]; 14
(1
): 263
PMID27612633
show ga
BACKGROUND: Moniliformediquinone (MFD), a phenanthradiquinone in Dendrobium
moniliforme, was synthesized in our laboratory. Beyond its in vitro inhibitory
effects on cancer cells, other biological activity of MFD is unknown. The purpose
of the present study was to investigate the effects of MFD on hepatic
fibrogenesis in vitro and in vivo. METHODS: Hepatic stellate HSC-T6 was cultured.
Cell viability assay and western blot analyses were performed. Male ICR mice were
evaluated on CCl4-induced hepatotoxicity using both histological examination and
immunohistochemical staining. RESULTS: First, in vitro study showed that the
synthesized MFD effectively attenuated the expression of transforming growth
factor-?1 (TGF-?1), connective tissue growth factor (CTGF), ?-smooth muscle actin
(?-SMA), and type I collagen (COL-1), which modulated the hepatic fibrogenesis.
Furthermore, MFD reduced the phosphorylation of p65 NF?B in HSC-T6 cells. In
vivo, liver fibrosis was induced by CCl4 twice a week for 10 weeks in mice. The
administration of the MFD was started after 1 week of CCl4 thrice-weekly; the MFD
significantly reduced plasma aspartate transaminase (AST) and lactose
dehydrogenase (LDH) as well as hepatic hydroxy-proline, ?-SMA, and COL-1
expression in CCl4-treated mice. Pathological analysis showed that the MFD
alleviated CCl4-induced hepatic inflammation, necrosis and fibrosis. These
results suggest that MFD possesses therapeutic potential for liver fibrosis.
CONCLUSIONS: The synthesized MFD exhibits anti-fibrotic potential by inactivation
of HSCs in vitro and decreases mouse hepatic fibrosis in vivo. Further
investigation into their clinical therapeutic potential is required.