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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

Main HPLC fingerprinting of iYGJ decoction. S1: verbascoside; S2: ferulic acid
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Fig1: Main HPLC fingerprinting of iYGJ decoction. S1: verbascoside; S2: ferulic acid

Mentions: The analysis of the iYGJ fingerprint was performed on a Waters 2695 HPLC system equipped with a vacuum degasser, a quaternary pump, an autosampler and a Waters 2487 UV detector system, connected to Waters Empower software. A Diamonsil C18 column (250 mm × 4.6 mm, 5 μm) was used for separation. Optimum separation was achieved using gradient elution with 0.5 % formic acid in water (A) and methanol (B): 0–10 min (5 %B–10 %B), 10–60 min (10 %B–20 %B), 60–100 min (20 %B–40 %B), 100–120 min (40–90 %B), 120–130 min (90 %B). The flow rate was set at 1.0 ml/min and the injection volume was 20 μl. Column temperature was maintained at 30 and UV detection was read at 330 nm. The HPLC fingerprint of iYGJ is illustrated in Fig. 1.Fig. 1


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)

Main HPLC fingerprinting of iYGJ decoction. S1: verbascoside; S2: ferulic acid
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Main HPLC fingerprinting of iYGJ decoction. S1: verbascoside; S2: ferulic acid
Mentions: The analysis of the iYGJ fingerprint was performed on a Waters 2695 HPLC system equipped with a vacuum degasser, a quaternary pump, an autosampler and a Waters 2487 UV detector system, connected to Waters Empower software. A Diamonsil C18 column (250 mm × 4.6 mm, 5 μm) was used for separation. Optimum separation was achieved using gradient elution with 0.5 % formic acid in water (A) and methanol (B): 0–10 min (5 %B–10 %B), 10–60 min (10 %B–20 %B), 60–100 min (20 %B–40 %B), 100–120 min (40–90 %B), 120–130 min (90 %B). The flow rate was set at 1.0 ml/min and the injection volume was 20 μl. Column temperature was maintained at 30 and UV detection was read at 330 nm. The HPLC fingerprint of iYGJ is illustrated in Fig. 1.Fig. 1

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