Abstract
Activity-directed fractionation and purification processes were employed to identify xanthine oxidase (XO) inhibitory compounds from the leaves of Perilla frutescens. The total extract was evaluated in vitro on XO inhibitory activity and in vivo in an experimental model with potassium oxonate-induced hyperuricemia in mice which was used to evaluate anti-hyperuricemic activity. The crude extract showed expressive urate-lowering activity results. Solvent partitioning of the total extract followed by macroporous resin column chromatography of the n-butanol extract yielded four extracts and eluted parts. Among them, only the 70% ethanol eluted part of the n-butanol extract showed strong activity and therefore was subjected to separation and purification using various chromatographic techniques. Five compounds showing potent activity were identified by comparing their spectral data with literature values to be caffeic acid, vinyl caffeate, rosmarinic acid, methyl rosmarinate, and apigenin. These results indicate that pending further study, these compounds could be used as novel natural product agents for the treatment of hyperuricemia.
Highlights
Hyperuricemia is characterized by an abnormally high level of uric acid in the blood due to a metabolic disorder on its production or on its excretion [1]
Serum uric acid levels were elevated to 300.7 ± 20.8 μmol/L 2 h after intraperitoneal injection of potassium oxonate
The serum uric acid levels of the hyperuricemic group orally treated with the water extracts of P. frutescens leaves at doses of 500, 1000, and 2000 mg/kg for 7 days were significantly lowered to 193.7 ± 9.9, 188.7 ± 5.9, and 131.0 ± 10.4 μmol/L, respectively
Summary
Hyperuricemia is characterized by an abnormally high level of uric acid in the blood due to a metabolic disorder on its production or on its excretion [1]. Increasing clinical reports have shown that hyperuricemia is associated with an increasing risk of gout, and cardiovascular disorders, renal dysfunction, hyperlipidemia, hypertension, cancer, diabetes and metabolic syndromes [2,3,4,5] Lifestyle modifications such as weight reduction, decreased dietary purine intake and alcohol consumption may help to decrease blood uric acid, but many patients will still need medication to control their hyperuricemia. Severe adverse effects in some patients, including fever, skin rashes, allergic reactions, hepatitis, and nephropathy limit the clinical use of allopurinol [6] For this reason, xanthine oxidase inhibitors from natural products have been explored as viable, harmless, and nontoxic alternatives for the treatment of hyperuricemia [7,8,9]
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