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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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Effect of astaxanthin on the regulation of autophagy in HSCs. (a) The analysis of western blotting showed that astaxanthin (40 mg/kg and 80 mg/kg) obviously decreased the expression of LC3-II and beclin-1. (b) The mRNA levels of beclin-1 were decreased by astaxanthin (40 mg/kg and 80 mg/kg) compared to CCL4 group, and the level of LC3 was decreased only with the dose of 80 mg/kg. Data are expressed as mean ± SD (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4). (c) The areas of positive cells of LC3 and beclin-1, mainly expressed in HSCs as showed, were visibly diminished by astaxanthin (40 mg/kg and 80 mg/kg) (original magnification: ×200). (d) The IODs of LC3 and beclin-1 were analyzed by Image-pro Plus 6.0. There existed a significant decrease with astaxanthin (40 mg/kg and 80 mg/kg) treatment (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4).
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fig5: Effect of astaxanthin on the regulation of autophagy in HSCs. (a) The analysis of western blotting showed that astaxanthin (40 mg/kg and 80 mg/kg) obviously decreased the expression of LC3-II and beclin-1. (b) The mRNA levels of beclin-1 were decreased by astaxanthin (40 mg/kg and 80 mg/kg) compared to CCL4 group, and the level of LC3 was decreased only with the dose of 80 mg/kg. Data are expressed as mean ± SD (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4). (c) The areas of positive cells of LC3 and beclin-1, mainly expressed in HSCs as showed, were visibly diminished by astaxanthin (40 mg/kg and 80 mg/kg) (original magnification: ×200). (d) The IODs of LC3 and beclin-1 were analyzed by Image-pro Plus 6.0. There existed a significant decrease with astaxanthin (40 mg/kg and 80 mg/kg) treatment (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4).

Mentions: Autophagy can exacerbate liver fibrosis through the degradation of lipid droplets to provide energy. In this study, we determined the expression of LC3 and beclin-1 in all groups, which could indicate the level of autophagy. The expression of LC3 and beclin-1 decreased following astaxanthin (40 mg/kg and 80 mg/kg) administration both at the mRNA and protein levels (Figures 5(a) and 5(b). Immunohistochemical staining showed that LC3 and beclin-1 were mainly expressed in the cytoplasm of HSCs, and the areas of positive cells were significantly decreased by astaxanthin (40 mg/kg and 80 mg/kg) (Figure 5(c)), analyzed with Image-Pro Plus 6.0. In addition, we used electron microscopy to observe autophagosomes. Compared with the control group, increased lysosomes and autophagosomes were observed in the CCL4-treated group. As expected, following astaxanthin administration, cell structure showed more integrity, with fewer lysosomes and autophagosomes (Figure 6). These results indicated that astaxanthin might attenuate liver fibrosis through downregulation of autophagy in HSCs.


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 the regulation of autophagy in HSCs. (a) The analysis of western blotting showed that astaxanthin (40 mg/kg and 80 mg/kg) obviously decreased the expression of LC3-II and beclin-1. (b) The mRNA levels of beclin-1 were decreased by astaxanthin (40 mg/kg and 80 mg/kg) compared to CCL4 group, and the level of LC3 was decreased only with the dose of 80 mg/kg. Data are expressed as mean ± SD (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4). (c) The areas of positive cells of LC3 and beclin-1, mainly expressed in HSCs as showed, were visibly diminished by astaxanthin (40 mg/kg and 80 mg/kg) (original magnification: ×200). (d) The IODs of LC3 and beclin-1 were analyzed by Image-pro Plus 6.0. There existed a significant decrease with astaxanthin (40 mg/kg and 80 mg/kg) treatment (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: Effect of astaxanthin on the regulation of autophagy in HSCs. (a) The analysis of western blotting showed that astaxanthin (40 mg/kg and 80 mg/kg) obviously decreased the expression of LC3-II and beclin-1. (b) The mRNA levels of beclin-1 were decreased by astaxanthin (40 mg/kg and 80 mg/kg) compared to CCL4 group, and the level of LC3 was decreased only with the dose of 80 mg/kg. Data are expressed as mean ± SD (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4). (c) The areas of positive cells of LC3 and beclin-1, mainly expressed in HSCs as showed, were visibly diminished by astaxanthin (40 mg/kg and 80 mg/kg) (original magnification: ×200). (d) The IODs of LC3 and beclin-1 were analyzed by Image-pro Plus 6.0. There existed a significant decrease with astaxanthin (40 mg/kg and 80 mg/kg) treatment (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4).
Mentions: Autophagy can exacerbate liver fibrosis through the degradation of lipid droplets to provide energy. In this study, we determined the expression of LC3 and beclin-1 in all groups, which could indicate the level of autophagy. The expression of LC3 and beclin-1 decreased following astaxanthin (40 mg/kg and 80 mg/kg) administration both at the mRNA and protein levels (Figures 5(a) and 5(b). Immunohistochemical staining showed that LC3 and beclin-1 were mainly expressed in the cytoplasm of HSCs, and the areas of positive cells were significantly decreased by astaxanthin (40 mg/kg and 80 mg/kg) (Figure 5(c)), analyzed with Image-Pro Plus 6.0. In addition, we used electron microscopy to observe autophagosomes. Compared with the control group, increased lysosomes and autophagosomes were observed in the CCL4-treated group. As expected, following astaxanthin administration, cell structure showed more integrity, with fewer lysosomes and autophagosomes (Figure 6). These results indicated that astaxanthin might attenuate liver fibrosis through downregulation of autophagy in HSCs.

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