Pharmacological mechanisms of the water leaves extract of Lysiphyllum strychnifolium for its anti-inflammatory and anti-hyperuricemic actions for gout treatment

Background: There have been anecdotal reports from Thai hyperuricemic patients that the leaves of Lysiphyllum strychnifolium could reduce plasma uric acid level and relieve inflammation of gout. However, no research to support these effects has been conducted. Objectives: This study was aimed to evaluate the anti-inflammatory and hypouricemic effects of L. strychnifolium leaves extract and to investigate the pharmacological mechanisms of these effects. Materials and Methods: The anti-inflammatory effect of L. strychnifolium was evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Effects of L. strychnifolium on xanthine oxidase (XO) were examined in vitro and in vivo using potassium oxonate (PO)-induced hyperuricemic mice. In addition, the antioxidant activity of L. strychnifolium was determined. Results: L. strychnifolium significantly reduced the mRNA expression of cyclooxygenase-II, inducible nitric oxide synthase, transforming growth factor-β, and tumor necrosis factor-α in LPS-stimulated RAW 264.7 cells ( P 50 and K i of 231 μg/ml and 177 μg/ml, respectively. Oral administration of L. strychnifolium (100 and 200 mg/kg) significantly lowered the plasma uric concentration ( P P L. strychnifolium did not significantly decrease the protein expression of solute carrier family 22 member 12 in the renal cortex. Total phenolic and flavonoid contents were determined to be 197.8 ± 5.8 mg gallic acid equivalence/g extract and 32.2 ± 1.2 mg quercetin equivalent/g extract, respectively. The IC 50 of the inhibition of 2,2-diphenyl-1-picrylhydrazyl radical was 44.32 μg/ml. Conclusion: The present study first provided scientific evidence for the anti-inflammatory, anti-hyperuricemic and antioxidant effects of L. strychnifolium leaves extract in vitro and in vivo , suggesting the possibility of this plant to treat gout. Abbreviations used: ABTS: 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid); COX-II: Cyclooxygenase-II; DMEM: Dulbecco's modified Eagle medium; DPPH: 2,2-Diphenyl-1-picrylhydrazyl; FBS: Fetal bovine serum; FRAP: Ferric reducing antioxidant power; GAE: Gallic acid equivalence; GLUT9: Glucose transporter 9; iNOS: Inducible nitric oxide synthase; LPS: Lipopolysaccharide; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; PO: Potassium oxonate; P/S: Penicillin/streptomycin; QE: Quercetin equivalent; SLC22A12: Solute carrier family 22 member 12; TNF-α: Tumor necrosis factor-α; TGF-β: Transforming growth factor-β; URAT: Urate-anion transporter 1; XO: Xanthine oxidase.