The effects of Tao-Hong-Si-Wu on hepatic necroinflammatory activity and fibrosis in a murine model of chronic liver disease

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• 作者：Shengyan Xi^a ; ¹ ; ^{xishengyan@xmu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Mengmeng Shi^a ; ¹ ; Xueqiang Jiang^b ; Gerald Y. Minuk^c ; Yao Cheng^a ; Ying Peng^a ; Yuewen Gong^d ; Yangxinzi Xu^c ; Xinrong Wang^a ; Jiaqi Yang^d ; Lifeng Yue^e ; Yanhui Wang^a
• 关键词：THSWD ; Tao-Hong-Si-Wu decoction ; TCM ; traditional Chinese medicine ; CCl4 ; carbon tetrachloride ; VEGF ; vascular endothelial growth factor ; KDR ; kinase insert domain-containing receptor ; AST ; aspartate aminotransferase ; ALT ; alanine aminotransferase ; Alb ; albumin ; TBIL ; total bilirubin ; HA ; hyaluronic acid ; LN ; laminin ; ANOVA ; analysis of variance ; ELISA ; enzyme-linked immunosorbent assay ; HE ; hematoxylin and eosin
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：2 March 2016
• 年：2016
• 卷：180
• 期：Complete
• 页码：28-36
• 全文大小：4340 K

文摘

Tao-Hong-Si-Wu decoction (THSWD) is a traditional Chinese herbal medicine that has been used for centuries in the treatment of Chinese patients with chronic liver disease. Recently, THSWD has been reported to alter vascular endothelial growth factor (VEGF) induced angiogenesis, raising the possibility that in addition to its anti-inflammatory properties; THSWD might also inhibit hepatic blood flow associated fibrosis.

Aim

To document the effects of THSWD on hepatic necroinflammatory disease activity, fibrosis and VEGF signaling in a murine model of chronic liver disease.

Methods

Sixty adult mice were equally divided into six study groups. Five groups were exposed to subcutaneous carbon tetrachloride (0.1 ml/10 g BW) for six weeks. Three of the five groups were treated with different concentrations of THSWD (4.25, 8.50, 17.00 g/kg), one with 0.1 mg/kg of Colchicine (positive control), and one with physiologic saline (negative control). Mice in the sixth group were not exposed to CCl₄ and remained untreated (healthy controls). Liver enzymes/function tests, hyaluronic acid and laminin levels were measured in serum, and hepatic histology, VEGF, Flt-1 and kinase insert domain-containing receptor (KDR), Akt and phosphorylated Akt (pAkt) expression were documented in liver tissue at the end of treatment.

Results

Hepatic necroinflammatory disease activity and fibrosis were significantly attenuated in THSWD treated mice in a dose dependent manner. These beneficial results were similar and often exceeded those achieved with Colchicine. In addition, VEGF, Flt-1, KDR, Akt and pAkt mRNA and protein expression were reduced in TSHWD treated mice.

Conclusions

In this animal model of chronic liver disease, THSWD decreased hepatic necroinflammatory disease and fibrosis. Inhibition of VEGF expression and downstream signaling were associated with these findings. Further studies with this and other TCMs as treatment for chronic liver disease are warranted.