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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 HIF-1α. a Western blot quantified protein expression of HIF-1α. GAPDH expression was a control for equal protein loading. b Quantification of band intensities of expressed proteins. n = 3. c HIF-1α 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
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Fig5: Effects of YGJ and iYGJ on HIF-1α. a Western blot quantified protein expression of HIF-1α. GAPDH expression was a control for equal protein loading. b Quantification of band intensities of expressed proteins. n = 3. c HIF-1α 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: Western blot and RT-PCR combined to indicate that expression of HIF-1α was significantly increased in the CCl4 group compared controls. As expected, protein and gene expressions of HIF-1α were all down regulated significantly by YGJ and iYGJ (P < 0.05). Also, the extent of YGJ and iYGJ in HIF-1α protein down-regulation was greater than after sorafenib treatment (Fig. 5).Fig. 5


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 HIF-1α. a Western blot quantified protein expression of HIF-1α. GAPDH expression was a control for equal protein loading. b Quantification of band intensities of expressed proteins. n = 3. c HIF-1α 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

Fig5: Effects of YGJ and iYGJ on HIF-1α. a Western blot quantified protein expression of HIF-1α. GAPDH expression was a control for equal protein loading. b Quantification of band intensities of expressed proteins. n = 3. c HIF-1α 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: Western blot and RT-PCR combined to indicate that expression of HIF-1α was significantly increased in the CCl4 group compared controls. As expected, protein and gene expressions of HIF-1α were all down regulated significantly by YGJ and iYGJ (P < 0.05). Also, the extent of YGJ and iYGJ in HIF-1α protein down-regulation was greater than after sorafenib treatment (Fig. 5).Fig. 5

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