The dual actions of Sanmiao wan as a hypouricemic agent: down-regulation of hepatic XOD and renal mURAT1 in hyperuricemic mice.
BACKGROUND
Sanmiao wan (SMW) is widely used for the treatment of gout and hyperuricemia in traditional Chinese medicine.


OBJECTIVE
The aim of the present study was to investigate the hypouricemic effects of SMW and its possible mechanism in potassium oxonate-induced hyperuricemic mice.


METHODS
SMW at 489, 978 and 1956 mg/kg was orally administered to hyperuricemic and normal mice, and standard drug allopurinol (2.5mg/kg) was served as a positive control. The effects of SMW on serum, urine and liver levels of uric acid, serum levels of creatinine, and activity of hepatic xanthine oxidase (XOD) were measured in mice. Moreover, the effects of SMW on the mRNA and protein levels of hepatic XOD and renal urate transporter 1 (mURAT1) in mice were analyzed by semi-quantitative RT-PCR and Western blotting methods, respectively.


RESULTS
SMW significantly reduced uric acid levels in serum and liver, inhibited hepatic XOD activity, mRNA and protein levels in hyperuricemic mice. Furthermore, SMW could effectively down-regulate renal mURAT1 mRNA and protein levels of hyperuricemic mice. And it reversed oxonate-induced elevation in serum creatinine levels of mice. However, SMW did not show any effects in normal mice.


CONCLUSIONS
These findings suggested that SMW produced dual hypouricemic actions by suppressing hepatic XOD to reduce uric acid production and down-regulating renal mURAT1 to decrease urate reabsorption and enhance urate excretion in hyperuricemic mice.
Wang
Xing
X
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Han kou Road 22, Nanjing 210093, PR China.
Wang
Cai-Ping
CP
Hu
Qing-Hua
QH
Lv
Yao-Zhong
YZ
Zhang
Xian
X
Ouyang
Zhen
Z
Kong
Ling-Dong
LD
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D015536:Down-Regulation; D006074:Gout Suppressants / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014969:Xanthine Oxidase / Q000378:metabolism*
D017931:DNA Primers; D006074:Gout Suppressants; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C109687:Slc22a12 protein, mouse; D000493:Allopurinol; D014969:Xanthine Oxidase