In vitro and in vivo evidence of hypouricemic and anti-inflammatory activities of Maclura cochinchinensis (Lour.) Corner heartwood extract

Abstract

Maclura cochinchinensis (Lour.) Corner (MC) heartwood extracts have been used for the treatment of gout, hyperuricemia, and inflammation in Thai traditional medicine. Despite their traditional use, their mechanisms of action remain unknown. The aim of this study was to determine the mechanisms of MC heartwood extract activity using both in vitro and in vivo models. The extraction methods were optimized to yield the highest contents of biochemical compounds and antioxidant activities. The effects of MC heartwood extract on xanthine oxidase and its enzyme kinetics were determined in vitro and the antihyperuricemic effect was evaluated in potassium oxonate (PO)-induced hyperuricemic mice. The anti-inflammatory effect of MC heartwood extract was also tested against lipopolysaccharide-induced proinflammatory mRNA upregulation in RAW 264.7 mouse macrophage cells. Soxhlet extraction of MC heartwood with 70% ethanol produced stronger antioxidant activity, and higher total phenolic and flavonoid contents than conventional methods did (maceration or decoction). By using HPLC, we found that MC contains morin as a major constituent, which may account for its pharmacological activities. Moreover, administration of MC heartwood extract (500 mg/kg) markedly decreased uric acid levels in PO-induced hyperuricemic mice (p < 0.05). MC heartwood extract inhibited the hepatic activity of xanthine oxidase ex vivo by approximately 53%. In addition, MC heartwood extract markedly downregulated mRNA expression of inflammatory mediators (TNF-α, TGF-β, iNOS, and COX-2) and this inhibition was comparable with that of dexamethasone. Therefore, MC heartwood extract is a promising candidate as a natural treatment for inflammation and the hyperuricemia that causes gout. Keywords: Maclura cochinchinensis, gout, Inflammation, Xanthine oxidase, Antioxidant