Luteolin-4'-O-glucoside and its aglycone, two major flavones of Gnaphalium affine D. Don, resist hyperuricemia and acute gouty arthritis activity in animal models

Background: Gnaphalium affine D. Don is a folk medicine of China believed to be efficacious in the treatment of many ailments, including hyperuricemia and gout. Purpose: Based on a previous study, we isolated two flavones, luteolin and luteolin-4'-O-glucoside, from G. affine. Our aim was to assess the potential beneficial effects of treatment and mechanisms of these two flavones on hyperuricemia and acute gouty arthritis. Methods: The model of potassium oxonate (PO)-induced hyperuricemia and monosodium urate (MSU) crystalinduced inflammation in mice has been established. We evaluated serum uric acid (Sur), xanthine oxidase (XO) activity, protein expression of urate transporter 1 (mURAT1) and glucose transporter 9 (mGLUT9) in renal and kidney protection in a hyperuricemia model. In addition, paw swelling and levels of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in serum were assessed in MSU crystal- induced mice. Results: Luteolin and luteolin-4'-O-glucoside showed a potent clinical effect in treating hyperuricemia and gout. We observed that the two flavones possess potent effect in hyperuricemia mice by decreasing the level of mURAT1 and inhibiting XO activity, which contribute to enhancing uric acid (UA) excretion and improving hyperuricemia-induced renal dysfunction. In addition, luteolin and luteolin-4'-O-glucoside also alleviated paw swelling and inflammation induced by MSU crystals. Further investigation implied that luteolin and luteolin-4'O-glucoside improved the symptoms of inflammation by decreasing the levels of IL-1 beta and TNF-alpha Conclusion: The present study suggests that luteolin and luteolin-4'-O-glucoside could be developed as therapeutics for treating hyperuricemia and gouty arthritis.