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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 liver injury. Histopathology was assessed with H&E (a, 200×) and Sirius red (b, 100×)
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Fig2: Effects of YGJ and iYGJ on CCl4-induced liver injury. Histopathology was assessed with H&E (a, 200×) and Sirius red (b, 100×)

Mentions: H&E staining revealed hepatocytes arranged in cords from central veins to portal area, with intact hepatic lobules in normal control mice. Damaged lobules and extensive necroinflammatory lesions were visible in CCl4 group livers. Compared to the CCl4 group, necroinflammatory hepatic lesions were reduced in groups treated with sorafenib, YGJ and iYGJ (Fig. 2a). Sirius red staining confirmed that modest collagen was present in the area of the portal and central veins in normal control mice, but in the CCl4 group, bridging collagen connecting the central veins and neighboring portal areas increased, and collagen fiber deposition was increased and pseudonodules were present. In contrast, in the sorafenib, YGJ and iYGJ groups, hepatic collagen deposition were significantly attenuated (Fig. 2b).Fig. 2


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 injury. Histopathology was assessed with H&E (a, 200×) and Sirius red (b, 100×)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Effects of YGJ and iYGJ on CCl4-induced liver injury. Histopathology was assessed with H&E (a, 200×) and Sirius red (b, 100×)
Mentions: H&E staining revealed hepatocytes arranged in cords from central veins to portal area, with intact hepatic lobules in normal control mice. Damaged lobules and extensive necroinflammatory lesions were visible in CCl4 group livers. Compared to the CCl4 group, necroinflammatory hepatic lesions were reduced in groups treated with sorafenib, YGJ and iYGJ (Fig. 2a). Sirius red staining confirmed that modest collagen was present in the area of the portal and central veins in normal control mice, but in the CCl4 group, bridging collagen connecting the central veins and neighboring portal areas increased, and collagen fiber deposition was increased and pseudonodules were present. In contrast, in the sorafenib, YGJ and iYGJ groups, hepatic collagen deposition were significantly attenuated (Fig. 2b).Fig. 2

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