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Cytotechnology

, Volume 71, Issue 1, pp 181–192 | Cite as

Anti-hyperuricemic effect of isorhamnetin in cultured hepatocytes and model mice: structure–activity relationships of methylquercetins as inhibitors of uric acid production

  • Shin-ichi AdachiEmail author
  • Shinji Kondo
  • Yusuke Sato
  • Fumiaki Yoshizawa
  • Kazumi Yagasaki
Article
  • 106 Downloads

Abstract

Hyperuricemia is an important risk factor for gout. Isorhamnetin (3′-O-methylquercetin) is an O-methylated flavonol, which occurs in onion, almond and sea buckthorn. It is also one of the metabolites of quercetin in mammals. In the present study, we investigated anti-hyperuricemic effect of isorhamnetin adopting both cultured hepatocytes and mice with hyperuricemia induced by purine bodies. In cultured hepatocytes, isorhamnetin as well as quercetin significantly and dose-dependently inhibited uric acid (UA) production. We also examined the inhibitory effects on UA production of other mono-methylquercetins, i.e., tamarixetin, 3-O-methylquercetin, azaleatin, and rhamnetin in addition to isorhamnetin for studying their structure–activity relationships. From the results obtained, hydroxyl groups at C-3, C-5, and especially C-7, but not C-3′ and C-4′ of quercetin are demonstrated to play a critical role in suppressing UA production in the AML12 hepatocytes. Oral administration of isorhamnetin significantly reduced plasma and hepatic UA levels in the hyperuricemic model mice. Isorhamnetin also decreased hepatic xanthine oxidase (XO) activity without changes in XO protein expression, indicating that anti-hyperuricemic effect of isorhamnetin could be, at least partly, attributable to suppression of UA production by directly inhibiting XO activity in the liver. These findings demonstrate that isorhamnetin has a potent anti-hyperuricemic effect and may be a potential candidate for prevention and remediation of hyperuricemia.

Keywords

Isorhamnetin AML12 hepatocyte Hyperuricemia Uric acid 

Abbreviations

BSS

Balanced salt solution

GMP

Guanosine-5′-monophosphate

IMP

Inosine-5′-monophosphate

UA

Uric acid

XO

Xanthine oxidase

Notes

Acknowledgements

This work was supported in part by the Reginal Innovation Strategy Support Program, MEXT, Japan, and in part by JSPS KAKENHI Grant Nos. JP16K16273 and JP15K07424. Authors are grateful to Keiichiro Numao, Kento Kobayashi, Kazusa Narita, Yuki Takami for their excellent technical assistance.

Compliance with ethical standards

Conflict of interest

Authors declare that they have no conflict of interest.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Shin-ichi Adachi
    • 1
    Email author
  • Shinji Kondo
    • 1
  • Yusuke Sato
    • 2
  • Fumiaki Yoshizawa
    • 2
    • 3
  • Kazumi Yagasaki
    • 1
  1. 1.Center for Bioscience Research and EducationUtsunomiya UniversityUtsunomiyaJapan
  2. 2.Faculty of AgricultureUtsunomiya UniversityUtsunomiyaJapan
  3. 3.Graduate School of Agricultural ScienceTokyo University of Agriculture and TechnologyTokyoJapan

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