title: Effects of Xie-Zhuo-Chu-Bi-Fang on miR-34a and URAT1 and their relationship in hyperuricemic mice.
abstract: BACKGROUND
  Xie-Zhuo-Chu-Bi-Fang (XZCBF) is an empirical formula that was developed based on the principles of traditional Chinese medicine, for the therapeutic purpose of treating hyperuricemia. XZCBF has been clinically utilized in the Department of Traditional Chinese Medicine at General Hospital of Guangzhou Military Command of PLA for many years and has exhibited favorable efficacy. The aim of the study is to evaluate the effects of XZCBF on the expression of uric acid transporter 1 (URAT1) and miR-34a in hyperuricemic mice and to determine, the correlation between the two expression levels.
  
  
  METHODS
  A hyperuricemic animal model was created by administering adenine and allantoxanic acid potassium salt to mice. The blood uric acid levels were measured in these model mice after treatment with XZCBF for 15 days. The potential targets of miR-34a were screened. The expression levels of miR-34a and URAT1 in the renal tissues collected from the model mice were determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and their correlation was further established by immunohistochemistry and in situ hybridization.
  
  
  RESULTS
  The uric acid levels in the model mice were significantly higher than those in the blank controls (P<0.05). These levels were significantly lower in the three groups receiving different doses of XZCBF (P<0.05), which was, in agreement with the downregulation of URAT1 and the upregulation of miR-34a in each group. The mRNA expression level of URAT1 was positively correlated with the concentration of uric acid but, negatively correlated with the expression level of miR-34a.
  
  
  CONCLUSIONS
  The ability of XZCBF to facilitate the excretion of uric acid and to lower its level in the model group was mediated by the upregulation of miR-34a and the inhibition of URAT1 mRNA expression, which suggests that XZCBF could be an option for the treatment of hyperuricemia in mice.
authors.affiliation: Department of Traditional Chinese Medicine, General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010, China. Electronic address: sunwf3@sina.com.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Sun
authors.affiliation: Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Ming-Min
authors.initials: MM
authors.lastname: Zhu
authors.affiliation: Department of Traditional Chinese Medicine, General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010, China; Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Traditional Chinese Medicine, General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010, China.
authors.forename: Xian-Xian
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: Department of Traditional Chinese Medicine, General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010, China.
authors.forename: Ying-Wan
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Department of Traditional Chinese Medicine, General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010, China. Electronic address: gzwxrong@yahoo.com.
authors.forename: Xin-Rong
authors.initials: XR
authors.lastname: Wu
authors.affiliation: Department of Traditional Chinese Medicine, General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Liu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006074:Gout Suppressants / Q000494:pharmacology* / Q000627:therapeutic use; D033461:Hyperuricemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation; D014527:Uric Acid / Q000097:blood
chemical_list: D004365:Drugs, Chinese Herbal; D006074:Gout Suppressants; C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C109687:Slc22a12 protein, mouse; C000601819:xie-zhuo-chu-bi-fang; D014527:Uric Acid
keywords: Astilbin (Pubchem CID: 119258); Colchicine (Pubchem CID: 6167); Ecdysterone (Pubchem CID: 5459840); Hyperuricemia; Kidney; URAT1; miR-34a