Abstract
Context: Chatuphalatika (CTPT), is a Thai herbal formulation mixture of Phyllanthus emblica Linn. (Euphorbiaceae), Terminalia belerica Linn. (Combretaceae), T. chebula and the fruit of T. arjuna (Roxb.) Wight & Arn. CTPT is considered to exert anti-inflammatory and antihyperuricemic effects, but there have been no reports to demonstrate these pharmacological effects in a quantitative manner.Objectives: To investigate the antioxidative, anti-inflammatory and antihyperuricemic effects of CTPT.Materials and methods: Antioxidant activities of CTPT extracts were measured in vitro by DPPH, ABTS and FRAP assays, and anti-inflammatory effect by measuring inflammatory mediator production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages. The mechanism of the hypouricemic effect was investigated using oxonate-induced hyperuricemic ddY mice treated with oral administrations of CTPT at 250, 500 and 1000 mg/kg.Results: Antioxidant activities of CTPT measured by ABTS and FRAP assays were 1.35 g TEAC/g extract and 10.3 mmol/100 g extract, respectively. IC50 for the inhibition of DPPH radical was 13.8 µg/mL. CTPT (10 µg/mL) significantly downregulated the mRNA expression of TNF-α and iNOS in RAW 264.7 cells. Lineweaver–Burk analysis of the enzyme kinetics showed that CTPT inhibited xanthine oxidase (XOD) activity in a noncompetitive manner with the Ki of 576.9 µg/mL. Oral administration of CTPT (1000 mg/kg) significantly suppressed uric acid production by inhibiting hepatic XOD activity, and decreased plasma uric acid levels in hyperuricemic mice by approximately 40% (p < 0.05).Conclusions: This study demonstrated for the first time the antioxidative, anti-inflammatory and antihyperuricemic effects of CTPT in vivo and in vitro, suggesting a possibility of using CTPT for the treatment of hyperuricemia in gout.
Highlights
Hyperuricemia has been established as a major risk factor in gout, which is caused by excess uric acid in blood due to increased production of uric acid and/or impaired renal urate excretion
The present results showed that allopurinol, a strong hepatic xanthine oxidase (XOD) inhibitor, had no effect on renal GLUT9 expression in hyperuricemic mice, which is consistent with a previous study (Hou et al 2012)
This study demonstrated for the first time the antioxidative, antiinflammatory and antihyperuricemic effects of CTPT extract in vivo and in vitro
Summary
Hyperuricemia has been established as a major risk factor in gout, which is caused by excess uric acid in blood due to increased production of uric acid and/or impaired renal urate excretion. During purine metabolism, increased xanthine oxidase (XOD) activity leads to the production of superoxide and uric acid. Until now, it has been unclear whether uric acid is an independent factor leading to cardiovascular disease and metabolic abnormalities. Epidemiological and biochemical studies examining uric acid formation have shown that uric acid leads to a worsening prognosis and increased cardiovascular events as do the free radicals and superoxides formed by xanthine oxidase activity. Allopurinol is the first-line drug for the treatment of hyperuricemia; an inadequate response is observed in some patients This drug may cause severe allergic hypersensitivity, such as Stevens–Johnson syndrome, especially in patients carrying the HLA-BÃ5801 allele (Kelkar et al 2011). Studies have focused on the development of agents possessing a safe combination of antiinflammatory, antioxidant and antihyperuricemic activities
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