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Effects of Xie-Zhuo-Chu-Bi-Fang on miR-34a and URAT1 and their relationship in hyperuricemic mice.

AbstractETHNOPHARMACOLOGICAL RELEVANCE:
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.
MATERIALS AND 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.
AuthorsWei-Feng Sun, Ming-Min Zhu, Jing Li, Xian-Xian Zhang, Ying-Wan Liu, Xin-Rong Wu, Zhi-Gang Liu
JournalJournal of ethnopharmacology (J Ethnopharmacol) Vol. 161 Pg. 163-9 (Feb 23 2015) ISSN: 1872-7573 [Electronic] Ireland
PMID25535087 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Chemical References
  • Drugs, Chinese Herbal
  • Gout Suppressants
  • MIRN34 microRNA, mouse
  • MicroRNAs
  • Organic Anion Transporters
  • RNA, Messenger
  • Slc22a12 protein, mouse
  • xie-zhuo-chu-bi-fang
  • Uric Acid
Topics
  • Animals
  • Disease Models, Animal
  • Drugs, Chinese Herbal (pharmacology, therapeutic use)
  • Gene Expression Regulation (drug effects)
  • Gout Suppressants (pharmacology, therapeutic use)
  • Hyperuricemia (blood, drug therapy, genetics, metabolism)
  • Kidney (drug effects, metabolism)
  • Male
  • Mice
  • MicroRNAs (genetics, metabolism)
  • Organic Anion Transporters (antagonists & inhibitors, genetics, metabolism)
  • RNA, Messenger (metabolism)
  • Up-Regulation
  • Uric Acid (blood)

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