Preprint / Version 1

Inhibitory Effects of Apium graveolens on Xanthine Oxidase Activity and Serum Uric Acid Levels in Hyperuricemic Mice

Authors

  • Karim Dolati Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
  • Hassan Rakhshandeh Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
  • Mohsen Golestani Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
  • Fatemeh Forouzanfar Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
  • Roya Sadeghnia Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
  • Hamid Sadeghnia Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran

Keywords:

Apium graveolens, hyperuricemia, xanthine dehydrogenase (XDH), xanthine oxidase (XO), hypouricemic agent

Abstract

Celery (Apium graveolens) is traditionally used to treat rheumatism and cardiovascular disorders. Hyperuricemia is considered as a predisposing factor for gout and is also suggested to be associated with coronary artery disease. In the present study, the effect of hydroalcoholic extracts from A. graveolens (AGE) against potassium oxonate (PO)-induced hyperuricemia was investigated in mice. AGE (250, 500, and 1,000 mg/kg) or allopurinol (5 mg/kg, as positive control) were orally administrated 1 h after PO injection (250 mg/kg, ip) for two weeks. After that, the serum uric acid level and hepatic xanthine dehydrogenase (XDH) and xanthine oxidase (XO) activities were measured. In addition, the antioxidant activity of AGE was determined by assessment of hepatic lipid peroxidation, in vivo and the ferric reducing/antioxidant power assay, in vitro. The extract exhibited good capacity to reduce ferric ion to ferrous ion with mean value of 63.8±8.5 μmol/g. The data also showed that oxonate treatment produced a significant increase in serum uric acid level (4.6 vs. 2.3 mg/ dL, P<0.001), liver XO/XDH activities (P<0.01 and P<0.001, respectively), and hepatic lipid peroxides levels (about two fold, P<0.01), compared to the healthy mice. AGE significantly decreased the serum uric acid level, hepatic XO/XDH activities, and lipid peroxidation, in a dose-dependent manner. Oral administration of 1,000 mg/kg AGE for two weeks reversed the elevated serum uric acid level (2.7 vs. 4.6 mg/dL, P<0.001) and significantly inhibited liver XO/XDH activities (P<0.001) and diminished hepatic lipid peroxidation (0.45 vs. 0.82 nmol/mg protein, P<0.05), compared with hyperuricemic mice. AGE (1,000 mg/kg) per se did not significantly modify these parameters. Our results demonstrated that AGE could reduce the serum uric acid level via inhibition of hepatic XDH/XO and indicated its potential utility as an effective hypouricemic bioactive agent or functional food. Keywords: Apium graveolens, hyperuricemia, xanthine dehydrogenase (XDH), xanthine oxidase (XO), hypouricemic agent

Author Biographies

Hassan Rakhshandeh, Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran

Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran

Hamid Sadeghnia, Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran

Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran

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