Phytochemicals from acacia confusa heartwood extracts reduce serum uric acid levels in oxonate-induced mice

Their potential use as xanthine oxidase inhibitors

Yu Tang Tung, Chih An Hsu, Chien Shu Chen, Suh Ching Yang, Chi Chang Huang, Shang Tzen Chang

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

In this study, the antihyperuricemic effect of Acacia confusa heartwood extracts and their phytochemicals on potassium oxonate (PO)-induced acute hyperuricemia was investigated for the first time. All treatments at the same dosage (100 mmol/kg) were administered to the abdominal cavity of PO-induced hyperuricemic mice, and serum uric acid level was measured at 3 h after administration. In experimental mice, serum uric acid level was significantly suppressed by the administration of A. confusa heartwood extracts and their major phytochemicals, (-)-2,3-cis-3,4-cis-3,3′,4,4′,7,8- hexahydroxyflavan, (-)-2,3-cis-3,4-cis-4′-methoxy-3,3′,4,7,8- pentahydroxyflavan, melanoxetin, transilitin, and okanin, relative to the PO group. The direct inhibitory effect of these five compounds on xanthine oxidase (XOD) activity was examined using isothermal titration calorimetry (ITC). Among them, melanoxetin showed a more remarkable inhibitory effect on XOD activity than allopurinol, a clinical drug used for XOD inhibitor. To further understand the stereochemistry between XOD and melanoxetin (or allopurinol), structure-based molecular modeling was performed. Melanoxetin undergoes extended interactions in the hydrophobic region via the 3′,4′- dihydroxyphenyl moiety, thus accounting for its higher binding affinity to XOD than allopurinol. These results indicate that A. confusa heartwood extracts and their major phytochemicals exhibit strong XOD inhibitory effects, which reduce serum uric acid levels while inhibiting uric acid generation in purine metabolism.

Original languageEnglish
Pages (from-to)9936-9941
Number of pages6
JournalJournal of Agricultural and Food Chemistry
Volume58
Issue number18
DOIs
Publication statusPublished - Sep 22 2010

Fingerprint

Acacia confusa
Acacia
xanthine oxidase
Xanthine Oxidase
heartwood
Phytochemicals
uric acid
Uric Acid
phytopharmaceuticals
allopurinol
Allopurinol
mice
extracts
Serum
potassium
Gout Suppressants
hyperuricemia
Hyperuricemia
Calorimetry
Stereochemistry

Keywords

  • Acacia confusa
  • hyperuricemia
  • isothermal titration calorimetry
  • melanoxetin
  • molecular docking
  • xanthine oxidase

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

Cite this

Phytochemicals from acacia confusa heartwood extracts reduce serum uric acid levels in oxonate-induced mice : Their potential use as xanthine oxidase inhibitors. / Tung, Yu Tang; Hsu, Chih An; Chen, Chien Shu; Yang, Suh Ching; Huang, Chi Chang; Chang, Shang Tzen.

In: Journal of Agricultural and Food Chemistry, Vol. 58, No. 18, 22.09.2010, p. 9936-9941.

Research output: Contribution to journalArticle

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abstract = "In this study, the antihyperuricemic effect of Acacia confusa heartwood extracts and their phytochemicals on potassium oxonate (PO)-induced acute hyperuricemia was investigated for the first time. All treatments at the same dosage (100 mmol/kg) were administered to the abdominal cavity of PO-induced hyperuricemic mice, and serum uric acid level was measured at 3 h after administration. In experimental mice, serum uric acid level was significantly suppressed by the administration of A. confusa heartwood extracts and their major phytochemicals, (-)-2,3-cis-3,4-cis-3,3′,4,4′,7,8- hexahydroxyflavan, (-)-2,3-cis-3,4-cis-4′-methoxy-3,3′,4,7,8- pentahydroxyflavan, melanoxetin, transilitin, and okanin, relative to the PO group. The direct inhibitory effect of these five compounds on xanthine oxidase (XOD) activity was examined using isothermal titration calorimetry (ITC). Among them, melanoxetin showed a more remarkable inhibitory effect on XOD activity than allopurinol, a clinical drug used for XOD inhibitor. To further understand the stereochemistry between XOD and melanoxetin (or allopurinol), structure-based molecular modeling was performed. Melanoxetin undergoes extended interactions in the hydrophobic region via the 3′,4′- dihydroxyphenyl moiety, thus accounting for its higher binding affinity to XOD than allopurinol. These results indicate that A. confusa heartwood extracts and their major phytochemicals exhibit strong XOD inhibitory effects, which reduce serum uric acid levels while inhibiting uric acid generation in purine metabolism.",
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