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Yiguanjian decoction and its ingredients inhibit angiogenesis in carbon tetrachloride-induced cirrhosis mice.

Zhou YN, Mu YP, Fu WW, Ning BB, Du GL, Chen JM, Sun MY, Zhang H, Hu YY, Liu CH, Xu LM, Liu P - BMC Complement Altern Med (2015)

Bottom Line: Both YGJ and iYGJ improved serum biochemistries.Compared to the CCl4 treated animals, Hyp, α-SMA, collagen I, CD31, VEGF, VEGFR, and HIF-1α expression decreased in YGJ and iYGJ groups.YGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated with CCl4 by inhibiting the HIF-1α/VEGF signaling pathway, suggesting that anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic hypoxic microenvironment.

View Article: PubMed Central - PubMed

Affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. zhouyaning103@sina.com.

ABSTRACT

Background: Cirrhosis is associated with angiogenesis and disruption of hepatic vascular architecture. Yiguanjian (YGJ) decoction, a prescription from traditional Chinese medicine, is widely used for treating liver diseases. We studied whether YGJ or its ingredients (iYGJ) had an anti-angiogenic effect and explored possible mechanisms underlying this process.

Methods: Cirrhosis was induced with carbon tetrachloride (CCl4) (ip) in C57BL/6 mice for 6 weeks. From week 4 to week 6, cirrhotic mice were randomly divided into four groups: sorafenib-treated, YGJ-treated and iYGJ-treated mice and placebo. Serum biochemistries, hydroxyproline (Hyp) content and histopathological changes of hepatic tissues were measured as were α-smooth muscle actin (α-SMA), collagen I, CD31, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) 2 and hypoxia-inducible factor (HIF)-1α.

Results: Both YGJ and iYGJ improved serum biochemistries. Changes of histopathology showed that YGJ and iYGJ reduced hepatic tissue necroinflammatory and collagen fiber deposition in cirrhosis mice. Compared to the CCl4 treated animals, Hyp, α-SMA, collagen I, CD31, VEGF, VEGFR, and HIF-1α expression decreased in YGJ and iYGJ groups.

Conclusions: YGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated with CCl4 by inhibiting the HIF-1α/VEGF signaling pathway, suggesting that anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic hypoxic microenvironment.

No MeSH data available.


Related in: MedlinePlus

Effects of YGJ and iYGJ on CCl4-induced activation of HSC. a Immunohistochemistry of liver sections for α-SMA and collagen I (200×). b Intensity of collagen I (A, below) was assessed by image analysis. n = 5. c Western blot quantified protein expression of α-SMA. GAPDH expression was a control for equal protein loading. d Quantification of band intensities of expressed proteins. n = 3. Quantitative data were reported as means ± SD. #, compared to control group P < 0.05; *, compared to CCl4 model group P < 0.05
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Fig3: Effects of YGJ and iYGJ on CCl4-induced activation of HSC. a Immunohistochemistry of liver sections for α-SMA and collagen I (200×). b Intensity of collagen I (A, below) was assessed by image analysis. n = 5. c Western blot quantified protein expression of α-SMA. GAPDH expression was a control for equal protein loading. d Quantification of band intensities of expressed proteins. n = 3. Quantitative data were reported as means ± SD. #, compared to control group P < 0.05; *, compared to CCl4 model group P < 0.05

Mentions: Immunohistochemistry indicated that accumulation of the active HSC marker α-SMA in livers increased in the CCl4 group. This change was consistent with protein expression of α-SMA analyzed by Western blot, which also increased after CCl4 injection. Increased expression of α-SMA was followed by enhanced collagen I synthesis. Semi-quantification of immunohistochemical staining revealed that collagen I increased sharply after CCl4 injection, 6.5-fold above control values. After treatment with sorafenib, YGJ or iYGJ, expression of α-SMA decreased according to immunohistochemistry data, and this agreed with data confirmed by Western blot. Thus, collagen I expression was significantly suppressed by sorafenib, YGJ or iYGJ treatment (P < 0.05; Fig. 3).Fig. 3


Yiguanjian decoction and its ingredients inhibit angiogenesis in carbon tetrachloride-induced cirrhosis mice.

Zhou YN, Mu YP, Fu WW, Ning BB, Du GL, Chen JM, Sun MY, Zhang H, Hu YY, Liu CH, Xu LM, Liu P - BMC Complement Altern Med (2015)

Effects of YGJ and iYGJ on CCl4-induced activation of HSC. a Immunohistochemistry of liver sections for α-SMA and collagen I (200×). b Intensity of collagen I (A, below) was assessed by image analysis. n = 5. c Western blot quantified protein expression of α-SMA. GAPDH expression was a control for equal protein loading. d Quantification of band intensities of expressed proteins. n = 3. Quantitative data were reported as means ± SD. #, compared to control group P < 0.05; *, compared to CCl4 model group P < 0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4591631&req=5

Fig3: Effects of YGJ and iYGJ on CCl4-induced activation of HSC. a Immunohistochemistry of liver sections for α-SMA and collagen I (200×). b Intensity of collagen I (A, below) was assessed by image analysis. n = 5. c Western blot quantified protein expression of α-SMA. GAPDH expression was a control for equal protein loading. d Quantification of band intensities of expressed proteins. n = 3. Quantitative data were reported as means ± SD. #, compared to control group P < 0.05; *, compared to CCl4 model group P < 0.05
Mentions: Immunohistochemistry indicated that accumulation of the active HSC marker α-SMA in livers increased in the CCl4 group. This change was consistent with protein expression of α-SMA analyzed by Western blot, which also increased after CCl4 injection. Increased expression of α-SMA was followed by enhanced collagen I synthesis. Semi-quantification of immunohistochemical staining revealed that collagen I increased sharply after CCl4 injection, 6.5-fold above control values. After treatment with sorafenib, YGJ or iYGJ, expression of α-SMA decreased according to immunohistochemistry data, and this agreed with data confirmed by Western blot. Thus, collagen I expression was significantly suppressed by sorafenib, YGJ or iYGJ treatment (P < 0.05; Fig. 3).Fig. 3

Bottom Line: Both YGJ and iYGJ improved serum biochemistries.Compared to the CCl4 treated animals, Hyp, α-SMA, collagen I, CD31, VEGF, VEGFR, and HIF-1α expression decreased in YGJ and iYGJ groups.YGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated with CCl4 by inhibiting the HIF-1α/VEGF signaling pathway, suggesting that anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic hypoxic microenvironment.

View Article: PubMed Central - PubMed

Affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. zhouyaning103@sina.com.

ABSTRACT

Background: Cirrhosis is associated with angiogenesis and disruption of hepatic vascular architecture. Yiguanjian (YGJ) decoction, a prescription from traditional Chinese medicine, is widely used for treating liver diseases. We studied whether YGJ or its ingredients (iYGJ) had an anti-angiogenic effect and explored possible mechanisms underlying this process.

Methods: Cirrhosis was induced with carbon tetrachloride (CCl4) (ip) in C57BL/6 mice for 6 weeks. From week 4 to week 6, cirrhotic mice were randomly divided into four groups: sorafenib-treated, YGJ-treated and iYGJ-treated mice and placebo. Serum biochemistries, hydroxyproline (Hyp) content and histopathological changes of hepatic tissues were measured as were α-smooth muscle actin (α-SMA), collagen I, CD31, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) 2 and hypoxia-inducible factor (HIF)-1α.

Results: Both YGJ and iYGJ improved serum biochemistries. Changes of histopathology showed that YGJ and iYGJ reduced hepatic tissue necroinflammatory and collagen fiber deposition in cirrhosis mice. Compared to the CCl4 treated animals, Hyp, α-SMA, collagen I, CD31, VEGF, VEGFR, and HIF-1α expression decreased in YGJ and iYGJ groups.

Conclusions: YGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated with CCl4 by inhibiting the HIF-1α/VEGF signaling pathway, suggesting that anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic hypoxic microenvironment.

No MeSH data available.


Related in: MedlinePlus