Journal
WORLD JOURNAL OF GASTROENTEROLOGY
Volume 21, Issue 18, Pages 5473-5481Publisher
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v21.i18.5473
Keywords
Dihydromyricetin; Liver regeneration; Tumor necrosis factor-alpha
Categories
Funding
- Guangdong Medical College [XB1338, M2013024]
- Medical Research Fund of Guangdong Province [B2014306]
Ask authors/readers for more resources
AIM: To assess the effects of dihydromyricetin (DHM) as a hepatoprotective candidate in reducing hepatic injury and accelerating hepatocyte proliferation after carbon tetrachloride (CCl4) treatment. METHODS: C57 BL/6 mice were used in this study. Mice were orally administered with DHM (150 mg/kg) for 4 d after CCl4 treatment. Serum and liver tissue samples were collected on days 1, 2, 3, 5 and 7 after CCl4 treatment. The anti-inflammatory effect of DHM was assessed directly by hepatic histology detection and indirectly by serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and superoxide dismutase (SOD). Inflammatory cytokines, such as interleukin (IL)-1 beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha), were detected using ELISA kits. Proliferating cell nuclear antigen (PCNA) staining was used to evaluate the role of DHM in promoting hepatocyte proliferation. Hepatocyte apoptosis was measured by TUNEL assay. Furthermore, apoptosis proteins Caspases-3, 6, 8, and 9 were detected by Western blot. SP600125 were used to confirm whether DHM regulated liver regeneration through JNK/TNF-alpha pathways. RESULTS: DHM showed a strong anti-inflammatory effect on CCl4-induced liver injury in mice. DHM could significantly decrease serum ALT, AST, IL-1 beta, IL-6 and TNF-alpha and increase serum albumin, SOD and liver SOD compared to the control group after CCl4 treatment (P < 0.05). PCNA results indicated that DHM could significantly increase the number of PCNA positive cells compared to the control (348.9 +/- 56.0 vs 107.1 +/- 31.4, P < 0.01). TUNEL assay showed that DHM dramatically reduced the number of apoptotic cells after CCl4 treatment compared to the control (365.4 +/- 99.4 vs 90.5 +/- 13.8, P < 0.01). Caspase activity detection showed that DHM could reduce the activities of Caspases-8, 3, 6 and 9 compared to the control (P < 0.05). The results of Western blot showed that DHM increased the expression of JNK and decreased TNF-alpha expression. However, DHM could not affect TNF-alpha expression after SP600125 treatment. Furthermore, DHM could significantly improve the survival rate of acute liver failure (ALF) mice (73.3% vs 20.0%, P < 0.0001), and SP600125 could inhibit the effect of DHM. CONCLUSION: These findings demonstrate that DHM alleviates CCl4-induced liver injury, suggesting that DHM is a promising candidate for reversing liver injury and ALF.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available