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Protective effect of astaxanthin on liver fibrosis through modulation of TGF-β1 expression and autophagy.

Shen M, Chen K, Lu J, Cheng P, Xu L, Dai W, Wang F, He L, Zhang Y, Chengfen W, Li J, Yang J, Zhu R, Zhang H, Zheng Y, Zhou Y, Guo C - Mediators Inflamm. (2014)

Bottom Line: The same results were confirmed in bile duct liagtion, (BDL) model.These results were simultaneously confirmed in vivo and in vitro.In conclusion, our study showed that 80 mg/kg astaxanthin had a significant protective effect on liver fibrosis by suppressing multiple profibrogenic factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, Shanghai 200072, China.

ABSTRACT
Liver fibrosis is a common pathway leading to cirrhosis and a worldwide clinical issue. Astaxanthin is a red carotenoid pigment with antioxidant, anticancer, and anti-inflammatory properties. The aim of this study was to investigate the effect of astaxanthin on liver fibrosis and its potential protective mechanisms. Liver fibrosis was induced in a mouse model using CCL4 (intraperitoneal injection, three times a week for 8 weeks), and astaxanthin was administered everyday at three doses (20, 40, and 80 mg/kg). Pathological results indicated that astaxanthin significantly improved the pathological lesions of liver fibrosis. The levels of alanine aminotransferase aspartate aminotransferase and hydroxyproline were also significantly decreased by astaxanthin. The same results were confirmed in bile duct liagtion, (BDL) model. In addition, astaxanthin inhibited hepatic stellate cells (HSCs) activation and formation of extracellular matrix (ECM) by decreasing the expression of NF-κB and TGF-β1 and maintaining the balance between MMP2 and TIMP1. In addition, astaxanthin reduced energy production in HSCs by downregulating the level of autophagy. These results were simultaneously confirmed in vivo and in vitro. In conclusion, our study showed that 80 mg/kg astaxanthin had a significant protective effect on liver fibrosis by suppressing multiple profibrogenic factors.

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Related in: MedlinePlus

Effect of astaxanthin on HSC-T6, NCTC1469, and RAW264.7 cells. (a) The proliferation of HSC-T6 was detected by MTT. (b) The levels of α-SMA, β-pdfgr, and collagen I were detected by western blot. (c) The levels of beclin-1, LC3, TGF-β1, Smad2, and Smad3 were detected by western blot. (d) The expression of α-SMA in HSC-T6 cells was detected by immunofluorescence. (e) The apoptosis of NCTC1469 cells was detected by flow cytometry (n = 3, *P < 0.05 for TGF-β1 + AST(40) versus TGF-β1). (f) The result of western blot showed that astaxanthin decreased the expression of NF-κB in RAW264.7 cells.
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fig7: Effect of astaxanthin on HSC-T6, NCTC1469, and RAW264.7 cells. (a) The proliferation of HSC-T6 was detected by MTT. (b) The levels of α-SMA, β-pdfgr, and collagen I were detected by western blot. (c) The levels of beclin-1, LC3, TGF-β1, Smad2, and Smad3 were detected by western blot. (d) The expression of α-SMA in HSC-T6 cells was detected by immunofluorescence. (e) The apoptosis of NCTC1469 cells was detected by flow cytometry (n = 3, *P < 0.05 for TGF-β1 + AST(40) versus TGF-β1). (f) The result of western blot showed that astaxanthin decreased the expression of NF-κB in RAW264.7 cells.

Mentions: The HSC-T6 cells were treated with increasing concentrations of astaxanthin in an MTT assay. Results showed that astaxanthin caused a dose-depended reduction in HSC-T6 cells (Figure 7(a)). It indicated that astaxanthin could inhibit the proliferation of HSC-T6 cells. Here, we also calculated the IC50, which was used in our following experiment. On the other hand, astaxanthin (IC50) obviously decreased the expression of α-SMA, collagen I, and β-PDGFR with western blot (Figure 7(b)). The expression of α-SMA was also confirmed using immunofluorescence (Figure 7(d)). These results indicated that the activation of HSC-T6 was inhibited by astaxanthin (IC50).


Protective effect of astaxanthin on liver fibrosis through modulation of TGF-β1 expression and autophagy.

Shen M, Chen K, Lu J, Cheng P, Xu L, Dai W, Wang F, He L, Zhang Y, Chengfen W, Li J, Yang J, Zhu R, Zhang H, Zheng Y, Zhou Y, Guo C - Mediators Inflamm. (2014)

Effect of astaxanthin on HSC-T6, NCTC1469, and RAW264.7 cells. (a) The proliferation of HSC-T6 was detected by MTT. (b) The levels of α-SMA, β-pdfgr, and collagen I were detected by western blot. (c) The levels of beclin-1, LC3, TGF-β1, Smad2, and Smad3 were detected by western blot. (d) The expression of α-SMA in HSC-T6 cells was detected by immunofluorescence. (e) The apoptosis of NCTC1469 cells was detected by flow cytometry (n = 3, *P < 0.05 for TGF-β1 + AST(40) versus TGF-β1). (f) The result of western blot showed that astaxanthin decreased the expression of NF-κB in RAW264.7 cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4016904&req=5

fig7: Effect of astaxanthin on HSC-T6, NCTC1469, and RAW264.7 cells. (a) The proliferation of HSC-T6 was detected by MTT. (b) The levels of α-SMA, β-pdfgr, and collagen I were detected by western blot. (c) The levels of beclin-1, LC3, TGF-β1, Smad2, and Smad3 were detected by western blot. (d) The expression of α-SMA in HSC-T6 cells was detected by immunofluorescence. (e) The apoptosis of NCTC1469 cells was detected by flow cytometry (n = 3, *P < 0.05 for TGF-β1 + AST(40) versus TGF-β1). (f) The result of western blot showed that astaxanthin decreased the expression of NF-κB in RAW264.7 cells.
Mentions: The HSC-T6 cells were treated with increasing concentrations of astaxanthin in an MTT assay. Results showed that astaxanthin caused a dose-depended reduction in HSC-T6 cells (Figure 7(a)). It indicated that astaxanthin could inhibit the proliferation of HSC-T6 cells. Here, we also calculated the IC50, which was used in our following experiment. On the other hand, astaxanthin (IC50) obviously decreased the expression of α-SMA, collagen I, and β-PDGFR with western blot (Figure 7(b)). The expression of α-SMA was also confirmed using immunofluorescence (Figure 7(d)). These results indicated that the activation of HSC-T6 was inhibited by astaxanthin (IC50).

Bottom Line: The same results were confirmed in bile duct liagtion, (BDL) model.These results were simultaneously confirmed in vivo and in vitro.In conclusion, our study showed that 80 mg/kg astaxanthin had a significant protective effect on liver fibrosis by suppressing multiple profibrogenic factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, Shanghai 200072, China.

ABSTRACT
Liver fibrosis is a common pathway leading to cirrhosis and a worldwide clinical issue. Astaxanthin is a red carotenoid pigment with antioxidant, anticancer, and anti-inflammatory properties. The aim of this study was to investigate the effect of astaxanthin on liver fibrosis and its potential protective mechanisms. Liver fibrosis was induced in a mouse model using CCL4 (intraperitoneal injection, three times a week for 8 weeks), and astaxanthin was administered everyday at three doses (20, 40, and 80 mg/kg). Pathological results indicated that astaxanthin significantly improved the pathological lesions of liver fibrosis. The levels of alanine aminotransferase aspartate aminotransferase and hydroxyproline were also significantly decreased by astaxanthin. The same results were confirmed in bile duct liagtion, (BDL) model. In addition, astaxanthin inhibited hepatic stellate cells (HSCs) activation and formation of extracellular matrix (ECM) by decreasing the expression of NF-κB and TGF-β1 and maintaining the balance between MMP2 and TIMP1. In addition, astaxanthin reduced energy production in HSCs by downregulating the level of autophagy. These results were simultaneously confirmed in vivo and in vitro. In conclusion, our study showed that 80 mg/kg astaxanthin had a significant protective effect on liver fibrosis by suppressing multiple profibrogenic factors.

Show MeSH
Related in: MedlinePlus