Limits...
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 liver angiogenesis. a Immunohistochemistry of liver sections for CD31 and VEGF (400×). b, f Western blot quantified protein expression of CD31, VEGF and VEGFR2. GAPDH expression was a control for equal protein loading. c, d, g Quantification of band intensities of expressed proteins. n = 3. e, h VEGF and VEGFR2 mRNA expression was measured by RT-PCR. 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
getmorefigures.php?uid=PMC4591631&req=5

Fig4: Effects of YGJ and iYGJ on CCl4-induced liver angiogenesis. a Immunohistochemistry of liver sections for CD31 and VEGF (400×). b, f Western blot quantified protein expression of CD31, VEGF and VEGFR2. GAPDH expression was a control for equal protein loading. c, d, g Quantification of band intensities of expressed proteins. n = 3. e, h VEGF and VEGFR2 mRNA expression was measured by RT-PCR. 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 revealed that CD31 and VEGF expression in the liver was up regulated after CCl4 treatment compared to controls. Notably, VEGF was observed not only in the hepatic sinusoid, but also in injured hepatocytes adjacent to the fibrotic septa around the portal area. In contrast, positive staining for CD31 and VEGF were decreased in the YGJ, iYGJ and sorafenib groups (Fig. 4a). Data from Western blot indicate that sorafenib, YGJ or iYGJ treatment reduced over-expression of CD31 and VEGF induced by CCl4, which is consistent with results of immunohistochemistry (P < 0.05; Fig. 4b, c, d). Moreover, VEGF mRNA was significantly increased in the CCl4 group compared to controls, but after sorafenib, YGJ or iYGJ treatment expression significantly decreased compared CCl4 treatment (P < 0.05; Fig. 4e). We next measured the effect of iYGJ on VEGFR2 with Western blot and PCR and noted that after CCl4 treatment, VEGFR2 expression was up regulated, but in the iYGJ treated group, VEGFR2 decreased markedly compared to the CCl4 group (P < 0.05; Fig. 4f, g, h).Fig. 4


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 liver angiogenesis. a Immunohistochemistry of liver sections for CD31 and VEGF (400×). b, f Western blot quantified protein expression of CD31, VEGF and VEGFR2. GAPDH expression was a control for equal protein loading. c, d, g Quantification of band intensities of expressed proteins. n = 3. e, h VEGF and VEGFR2 mRNA expression was measured by RT-PCR. 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

Fig4: Effects of YGJ and iYGJ on CCl4-induced liver angiogenesis. a Immunohistochemistry of liver sections for CD31 and VEGF (400×). b, f Western blot quantified protein expression of CD31, VEGF and VEGFR2. GAPDH expression was a control for equal protein loading. c, d, g Quantification of band intensities of expressed proteins. n = 3. e, h VEGF and VEGFR2 mRNA expression was measured by RT-PCR. 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 revealed that CD31 and VEGF expression in the liver was up regulated after CCl4 treatment compared to controls. Notably, VEGF was observed not only in the hepatic sinusoid, but also in injured hepatocytes adjacent to the fibrotic septa around the portal area. In contrast, positive staining for CD31 and VEGF were decreased in the YGJ, iYGJ and sorafenib groups (Fig. 4a). Data from Western blot indicate that sorafenib, YGJ or iYGJ treatment reduced over-expression of CD31 and VEGF induced by CCl4, which is consistent with results of immunohistochemistry (P < 0.05; Fig. 4b, c, d). Moreover, VEGF mRNA was significantly increased in the CCl4 group compared to controls, but after sorafenib, YGJ or iYGJ treatment expression significantly decreased compared CCl4 treatment (P < 0.05; Fig. 4e). We next measured the effect of iYGJ on VEGFR2 with Western blot and PCR and noted that after CCl4 treatment, VEGFR2 expression was up regulated, but in the iYGJ treated group, VEGFR2 decreased markedly compared to the CCl4 group (P < 0.05; Fig. 4f, g, h).Fig. 4

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