title: Huangqi decoction alleviates dimethylnitrosamine-induced liver fibrosis: An analysis of bile acids metabolic mechanism.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: synabc.123@163.com.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Song
authors.affiliation: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: kofy1234@163.com.
authors.forename: Gui-Biao
authors.initials: GB
authors.lastname: Zhang
authors.affiliation: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: ava0048@163.com.
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Lu
authors.affiliation: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: cqlw1975@126.com.
authors.forename: Qi-Long
authors.initials: QL
authors.lastname: Chen
authors.affiliation: Research Center for Traditional Chinese Medicine and System biology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203 China. Electronic address: cpuyl@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: wangzht@hotmail.com.
authors.forename: Zheng-Tao
authors.initials: ZT
authors.lastname: Wang
authors.affiliation: E-institutes of Traditional Chinese Internal Medicine, Shanghai Municipal Education Commission, Shanghai 201203, China. Electronic address: liuliver@vip.sina.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: shibingsu07@163.com.
authors.forename: Shi-Bing
authors.initials: SB
authors.lastname: Su
mesh_terms: D000818:Animals; D027885:Astragalus propinquus; D001647:Bile Acids and Salts / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D049109:Cell Proliferation / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002851:Chromatography, High Pressure Liquid; D004128:Dimethylnitrosamine; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods; D020011:Protective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D020011:Protective Agents; D012333:RNA, Messenger; C027492:Huang Qi; D004128:Dimethylnitrosamine; D006909:Hydroxyproline
keywords: Bile acid; Hepatic stellate cells; Huangqi decoction; Liver fibrosis; Metabolic mechanism