Document Detail

Phytochemicals from Acacia confusa heartwood extracts reduce serum uric acid levels in oxonate-induced mice: their potential use as xanthine oxidase inhibitors.
MedLine Citation:
PMID:  20806936     Owner:  NLM     Status:  MEDLINE    
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.
Yu-Tang Tung; Chih-An Hsu; Chien-Shu Chen; Suh-Ching Yang; Chi-Chang Huang; Shang-Tzen Chang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of agricultural and food chemistry     Volume:  58     ISSN:  1520-5118     ISO Abbreviation:  J. Agric. Food Chem.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-15     Completed Date:  2011-01-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374755     Medline TA:  J Agric Food Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9936-41     Citation Subset:  IM    
School of Forestry and Resource Conservation, National Taiwan University, Taipei 106, Taiwan.
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MeSH Terms
Acacia / chemistry*
Drug Discovery*
Enzyme Inhibitors / therapeutic use*,  toxicity
Flavonoids / chemistry,  isolation & purification,  therapeutic use*
Hyperuricemia / blood,  chemically induced,  drug therapy*
Mice, Inbred ICR
Oxonic Acid / toxicity
Plant Extracts / chemistry*,  therapeutic use
Urate Oxidase / antagonists & inhibitors
Uric Acid / blood
Wood / chemistry
Xanthine Oxidase / antagonists & inhibitors*,  chemistry
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Flavonoids; 0/Plant Extracts; 0/potassium oxonate; 69-93-2/Uric Acid; 937-13-3/Oxonic Acid; EC Oxidase; EC Oxidase

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