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Moniliformediquinone as a potential therapeutic agent, inactivation of hepatic stellate cell and inhibition of liver fibrosis in vivo

View Article: PubMed Central - PubMed

ABSTRACT

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-β1 (TGF-β1), connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and type I collagen (COL-1), which modulated the hepatic fibrogenesis. Furthermore, MFD reduced the phosphorylation of p65 NFκB 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, α-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.

No MeSH data available.


Effects of MFD on serum AST and LDH in CCl4-treated mice. The data for serum LDH and AST are presented as mean ± SD from six mice per group. #P < 0.05, as compared to the control group; *P < 0.05, as compared to the CCl4-treated group
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Fig3: Effects of MFD on serum AST and LDH in CCl4-treated mice. The data for serum LDH and AST are presented as mean ± SD from six mice per group. #P < 0.05, as compared to the control group; *P < 0.05, as compared to the CCl4-treated group

Mentions: In order to evaluate hepatic tissue damage, serum enzyme levels of LDH and AST with/without CCl4-treated mice were determined by using standard enzymatic kits. As shown in Fig. 3, serum LDH and AST activity in mice treated with MFD alone did not significantly differ from that of the control group. AST and LDH activity of all CCl4-treated mice increased significantly as compared with that of the control group after the end of the experiment (P < 0.001). However, administration of the MFD significantly suppressed the CCl4-induced increase of LDH and AST activity, respectively (P < 0.01, P < 0.001).Fig. 3


Moniliformediquinone as a potential therapeutic agent, inactivation of hepatic stellate cell and inhibition of liver fibrosis in vivo
Effects of MFD on serum AST and LDH in CCl4-treated mice. The data for serum LDH and AST are presented as mean ± SD from six mice per group. #P < 0.05, as compared to the control group; *P < 0.05, as compared to the CCl4-treated group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5017031&req=5

Fig3: Effects of MFD on serum AST and LDH in CCl4-treated mice. The data for serum LDH and AST are presented as mean ± SD from six mice per group. #P < 0.05, as compared to the control group; *P < 0.05, as compared to the CCl4-treated group
Mentions: In order to evaluate hepatic tissue damage, serum enzyme levels of LDH and AST with/without CCl4-treated mice were determined by using standard enzymatic kits. As shown in Fig. 3, serum LDH and AST activity in mice treated with MFD alone did not significantly differ from that of the control group. AST and LDH activity of all CCl4-treated mice increased significantly as compared with that of the control group after the end of the experiment (P < 0.001). However, administration of the MFD significantly suppressed the CCl4-induced increase of LDH and AST activity, respectively (P < 0.01, P < 0.001).Fig. 3

View Article: PubMed Central - PubMed

ABSTRACT

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-&beta;1 (TGF-&beta;1), connective tissue growth factor (CTGF), &alpha;-smooth muscle actin (&alpha;-SMA), and type I collagen (COL-1), which modulated the hepatic fibrogenesis. Furthermore, MFD reduced the phosphorylation of p65 NF&kappa;B in HSC-T6 cells. In vivo, liver fibrosis was induced by CCl4 twice a week for 10&nbsp;weeks in mice. The administration of the MFD was started after 1&nbsp;week of CCl4 thrice-weekly; the MFD significantly reduced plasma aspartate transaminase (AST) and lactose dehydrogenase (LDH) as well as hepatic hydroxy-proline, &alpha;-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.

No MeSH data available.