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Osthole ameliorates hepatic fibrosis and inhibits hepatic stellate cell activation.

Liu YW, Chiu YT, Fu SL, Huang YT - J. Biomed. Sci. (2015)

Bottom Line: Additionally, osthole reduced the expression of fibrosis-related genes significantly.Furthermore, osthole decreased TNF-α-triggered NF-κB activities significantly.In addition, osthole suppressed HSCs activation in vitro significantly.

View Article: PubMed Central - PubMed

Affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, No. 155, Li-Nong Street, Sec. 2, Taipei, 11221, Taiwan. yaweiliu19850417@gmail.com.

ABSTRACT

Background: Hepatic fibrosis is a dynamic process which ultimately leads to cirrhosis in almost patients with chronic hepatic injury. However, progressive fibrosis is a reversible scarring response. Activation of hepatic stellate cells (HSCs) is the prevailing process during hepatic fibrosis. Osthole is an active component majorly contained in the fruit of Cnidium monnieri (L.) Cusson. This present study investigated the therapeutic effects of osthole on rat liver fibrosis and HSC activation.

Results: We established the thioacetamide (TAA)-model of Sprague-Dawley (SD) rats to induce hepatic fibrosis. Rats were divided into three groups: control, TAA, and TAA + osthole (10 mg/kg). In vivo, osthole significantly reduced liver injury by diminishing levels of plasma AST and ALT, improving histological architecture, decreasing collagen and α-SMA accumulation, and improving hepatic fibrosis scores. Additionally, osthole reduced the expression of fibrosis-related genes significantly. Osthole also suppressed the production of fibrosis-related cytokines and chemokines. Moreover, nuclear translocation of p65 was significantly suppressed in osthole-treated liver. Osthole also ameliorated TAA-induced injury through reducing cellular oxidation. Osthole showed inhibitory effects in inflammation-related genes and chemokines production as well. In vitro, we assessed osthole effects in activated HSCs (HSC-T6 and LX-2). Osthole attenuated TGF-β1-induced migration and invasion in HSCs. Furthermore, osthole decreased TNF-α-triggered NF-κB activities significantly. Besides, osthole alleviated TGF-β1- or ET-1-induced HSCs contractility.

Conclusions: Our study demonstrated that osthole improved TAA-caused liver injury, fibrogenesis and inflammation in rats. In addition, osthole suppressed HSCs activation in vitro significantly.

No MeSH data available.


Related in: MedlinePlus

General profiles in control rats and TAA-induced fibrotic rats with or without osthole treatment. a Rat liver images from three groups: control rats were given only CMC (n = 8); and TAA-group rats were given CMC with TAA injection (n = 10); TAA + osthole-group rats were gavage osthole (10 mg/kg) in CMC with TAA injection (n = 10). The protocol of treatment was described in the Methods. Scale bar represents 1 cm for livers. b Plasma levels of ALT and AST from all groups. c Liver weight was recorded after sacrifice. Data are shown as mean ± SD of 8 rats in each group.*p < 0.05; **p < 0.01, compared with other groups
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Fig1: General profiles in control rats and TAA-induced fibrotic rats with or without osthole treatment. a Rat liver images from three groups: control rats were given only CMC (n = 8); and TAA-group rats were given CMC with TAA injection (n = 10); TAA + osthole-group rats were gavage osthole (10 mg/kg) in CMC with TAA injection (n = 10). The protocol of treatment was described in the Methods. Scale bar represents 1 cm for livers. b Plasma levels of ALT and AST from all groups. c Liver weight was recorded after sacrifice. Data are shown as mean ± SD of 8 rats in each group.*p < 0.05; **p < 0.01, compared with other groups

Mentions: To identify the therapeutic effect of osthole in TAA rats, we first observed the liver condition of each group. In macroscopic views, control livers showed smooth surface and brown color, but TAA-group livers displayed pink and numerous irregular nodules. Livers from TAA + osthole rats exhibited normally dark red color without surface nodularity (Fig. 1a). The mortality among three groups was not significantly different (Additional file 3: Figure S2). We further assessed the effect of osthole treatment on liver injury by biochemical analyses of plasma enzymes. TAA-injected rats showed significantly higher ALT and AST activities than control rats, suggesting hepatic injury due to TAA. Results also showed that the group had lower levels of ALT and AST than the TAA group (Fig. 1b). There was no renal impairment according to the value of creatinine in all groups (data none shown). The body weight of TAA-treated rats was significantly lighter than that of control rats, and there was no difference in body weight between TAA-treated rats with and without osthole treatment (Additional file 4: Figure S3). There was no difference in liver weight between control and TAA rats. However, TAA + osthole-treated rats showed a significant decrease in liver weight compared with TAA rats (Fig. 1c), suggesting that osthole treatment diminished hepatic injury in TAA rats.Fig. 1


Osthole ameliorates hepatic fibrosis and inhibits hepatic stellate cell activation.

Liu YW, Chiu YT, Fu SL, Huang YT - J. Biomed. Sci. (2015)

General profiles in control rats and TAA-induced fibrotic rats with or without osthole treatment. a Rat liver images from three groups: control rats were given only CMC (n = 8); and TAA-group rats were given CMC with TAA injection (n = 10); TAA + osthole-group rats were gavage osthole (10 mg/kg) in CMC with TAA injection (n = 10). The protocol of treatment was described in the Methods. Scale bar represents 1 cm for livers. b Plasma levels of ALT and AST from all groups. c Liver weight was recorded after sacrifice. Data are shown as mean ± SD of 8 rats in each group.*p < 0.05; **p < 0.01, compared with other groups
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522080&req=5

Fig1: General profiles in control rats and TAA-induced fibrotic rats with or without osthole treatment. a Rat liver images from three groups: control rats were given only CMC (n = 8); and TAA-group rats were given CMC with TAA injection (n = 10); TAA + osthole-group rats were gavage osthole (10 mg/kg) in CMC with TAA injection (n = 10). The protocol of treatment was described in the Methods. Scale bar represents 1 cm for livers. b Plasma levels of ALT and AST from all groups. c Liver weight was recorded after sacrifice. Data are shown as mean ± SD of 8 rats in each group.*p < 0.05; **p < 0.01, compared with other groups
Mentions: To identify the therapeutic effect of osthole in TAA rats, we first observed the liver condition of each group. In macroscopic views, control livers showed smooth surface and brown color, but TAA-group livers displayed pink and numerous irregular nodules. Livers from TAA + osthole rats exhibited normally dark red color without surface nodularity (Fig. 1a). The mortality among three groups was not significantly different (Additional file 3: Figure S2). We further assessed the effect of osthole treatment on liver injury by biochemical analyses of plasma enzymes. TAA-injected rats showed significantly higher ALT and AST activities than control rats, suggesting hepatic injury due to TAA. Results also showed that the group had lower levels of ALT and AST than the TAA group (Fig. 1b). There was no renal impairment according to the value of creatinine in all groups (data none shown). The body weight of TAA-treated rats was significantly lighter than that of control rats, and there was no difference in body weight between TAA-treated rats with and without osthole treatment (Additional file 4: Figure S3). There was no difference in liver weight between control and TAA rats. However, TAA + osthole-treated rats showed a significant decrease in liver weight compared with TAA rats (Fig. 1c), suggesting that osthole treatment diminished hepatic injury in TAA rats.Fig. 1

Bottom Line: Additionally, osthole reduced the expression of fibrosis-related genes significantly.Furthermore, osthole decreased TNF-α-triggered NF-κB activities significantly.In addition, osthole suppressed HSCs activation in vitro significantly.

View Article: PubMed Central - PubMed

Affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, No. 155, Li-Nong Street, Sec. 2, Taipei, 11221, Taiwan. yaweiliu19850417@gmail.com.

ABSTRACT

Background: Hepatic fibrosis is a dynamic process which ultimately leads to cirrhosis in almost patients with chronic hepatic injury. However, progressive fibrosis is a reversible scarring response. Activation of hepatic stellate cells (HSCs) is the prevailing process during hepatic fibrosis. Osthole is an active component majorly contained in the fruit of Cnidium monnieri (L.) Cusson. This present study investigated the therapeutic effects of osthole on rat liver fibrosis and HSC activation.

Results: We established the thioacetamide (TAA)-model of Sprague-Dawley (SD) rats to induce hepatic fibrosis. Rats were divided into three groups: control, TAA, and TAA + osthole (10 mg/kg). In vivo, osthole significantly reduced liver injury by diminishing levels of plasma AST and ALT, improving histological architecture, decreasing collagen and α-SMA accumulation, and improving hepatic fibrosis scores. Additionally, osthole reduced the expression of fibrosis-related genes significantly. Osthole also suppressed the production of fibrosis-related cytokines and chemokines. Moreover, nuclear translocation of p65 was significantly suppressed in osthole-treated liver. Osthole also ameliorated TAA-induced injury through reducing cellular oxidation. Osthole showed inhibitory effects in inflammation-related genes and chemokines production as well. In vitro, we assessed osthole effects in activated HSCs (HSC-T6 and LX-2). Osthole attenuated TGF-β1-induced migration and invasion in HSCs. Furthermore, osthole decreased TNF-α-triggered NF-κB activities significantly. Besides, osthole alleviated TGF-β1- or ET-1-induced HSCs contractility.

Conclusions: Our study demonstrated that osthole improved TAA-caused liver injury, fibrogenesis and inflammation in rats. In addition, osthole suppressed HSCs activation in vitro significantly.

No MeSH data available.


Related in: MedlinePlus