Huangqi decoction alleviates dimethylnitrosamine-induced liver fibrosis: An analysis of bile acids metabolic mechanism

详细信息    查看全文

• 作者：Ya-Nan Song^a ; ¹ ; ^{synabc.123@163.com" class="auth_mail" title="E-mail the corresponding author} ; Gui-Biao Zhang^a ; ¹ ; ^{kofy1234@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yi-Yu Lu^a ; ^{ava0048@163.com" class="auth_mail" title="E-mail the corresponding author} ; Qi-Long Chen^a ; ^{cqlw1975@126.com" class="auth_mail" title="E-mail the corresponding author} ; Li Yang^b ; ^{cpuyl@126.com" class="auth_mail" title="E-mail the corresponding author} ; Zheng-Tao. Wang^c ; ^{wangzht@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; Ping Liu^d ; ^{liuliver@vip.sina.com" class="auth_mail" title="E-mail the corresponding author} ; Shi-Bing Su^a ; ^{shibingsu07@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Bile acid ; Hepatic stellate cells ; Huangqi decoction ; Liver fibrosis ; Metabolic mechanism
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：2 August 2016
• 年：2016
• 卷：189
• 期：Complete
• 页码：148-156
• 全文大小：2091 K

文摘

Huangqi Decoction (HQD), a classical traditional Chinese medicine (TCM) formula, is used to treating liver injury in China. The aim of the study is to investigate mechanisms of HQD against dimethylnitrosamine (DMN)-induced liver fibrosis underlying metabolic profiles of bile acids.

Materials and methods

DMN-induced liver fibrosis rats were administrated HQD and its compounds, astragalosides (AS), glycyrrhizic acid (GA) and their combination. The anti-fibrosis effects were evaluated and targeted metabolomics by UPLC-MS was used to examine whether HQD had an influence on bile acid metabolism. The levels of mRNAs associated with bile acid metabolism were expressed by RT-PCR. Chenodeoxycholic acid (CDCA)-induced hepatic stellate cells (HSCs) proliferation and activation were examined using MTS assay and Western blot.

Results

Histopathological changes and serum liver function in HQD group had significant improvements (P<0.01). Concentrations of free bile acids and taurine conjugates were significantly increased in DMN group (P<0.05). HQD and its compounds restored the increased bile acids to normal levels, and HQD was more effected on parts of bile acids. Furthermore, the levels of mRNAs related bile acid synthesis and reabsorption such as CYP7A1, CYP8B1, CYP27A1, OATP2, OATP3, OATP4 and NTCP were significantly down-regulated in DMN group (P<0.05), mRNAs related excretion such as MRP3 and BESP were up-regulated (P<0.01), and CYP7A1, CYP8B1, OATP3, OATP4, NTCP and MRP3 restored to normal levels by HQD treatment. Moreover, CDCA-induced HSCs proliferation and activation were weaken by HQD (P<0.05) with down-regulated α-SMA, TGF-β1, p-Smad2 and p-Smad3 expressions.

Conclusions

HQD alleviated DMN-induced liver fibrosis with a better effect than its compounds, which may be involved in the regulation of bile acid metabolism enzyme. Moreover, HQD may inhibit CDCA-induced HSCs proliferation and activation.