肉桂醛缩氨基脲对黄嘌呤氧化酶的抑制作用研究

Inhibitory Effects of Cinnamic Aldehyde Semicarbazone on Activity of Xanthine Oxidase

摘要:

为研究肉桂醛缩氨基脲对黄嘌呤氧化酶（XOD）的抑制作用，以黄嘌呤为底物，测定肉桂醛缩氨基脲对黄嘌呤氧化酶活性的IC₅₀、抑制类型和抑制常数。抑制类型由Lineweaver-Burk双倒数作图法来判断，并计算相应的抑制常数（K_Ｉ和K_ＩＳ）。还研究了肉桂醛缩氨基脲对小鼠血尿酸质量浓度、血清XOD活性和肝脏XOD活性的影响。肉桂醛缩氨基脲对黄嘌呤氧化酶活性抑制效果显著，IC50为55.48 μmol/L，是混合型可逆抑制，抑制常数KＩ为27.25 μmol/L，K_ＩＳ为50.30 μmol/L。与模型组相比，肉桂醛缩氨基脲能显著降低小鼠血清尿酸质量浓度、血清XOD活性和肝脏XOD，呈显著性差异（P <0.05，n =10）。活性顺序是：别嘌呤醇>肉桂醛缩氨基脲>肉桂醛。肉桂醛缩氨基脲对黄嘌呤氧化酶活性抑制效果显著，能显著降低小鼠血尿酸质量浓度、血清XOD活性和肝脏XOD活性，是值得进一步研究的降低尿酸、治疗痛风的候选药物。

Abstract:

The inhibition mechanism of cinnamic aldehyde semicarbazone on xanthine oxidase activity was examined. The experiment examined the IC₅₀ values, inhibitory type, and the inhibitory constant value of cinnamic aldehyde semicarbazone on xanthine oxidase to analyze the oxidation of xanthine. The inhibition type was determined by Lineweaver - Burk double reciprocal plot and the corresponding inhibition constants (K_Ｉ and K_ＩＳ) were calculated. The experiment also examined the effects of cinnamic aldehyde semicarbazone on the concentration of serum uric acid，the activity of serum xanthine oxidase and liver xanthine oxidase in mice. Cinnamic aldehyde semicarbazone showed significant inhibitory effects on the activity of xanthine oxidase with IC₅₀ of 55.48 μmol/L，and it was the reversible inhibitor and competitive-uncompetitive mixed type inhibitor with K_Ｉ of 27.25 μmol/L and K_ＩＳ of 50.30 μmol/L. Compared with the model group, cinnamic aldehyde semicarbazone could significantly reduce the concentration of serum uric acid，the activity of serum xanthine oxidase and liver xanthine oxidase in mice (P <0.05，n =10). The active sequence was allopurinol>cinnamic aldehyde semicarbazone>cinnamyl aldehyde. Cinnamic aldehyde semicarbazone had significant inhibitory effects on the activity of xanthine oxidase. It could also significantly reduce the concentration of serum uric acid, the activity of serum xanthine oxidase and liver xanthine oxidase in mice. These results suggest the utilization of cinnamic aldehyde semicarbazone as a new drug candidate for reducing uric acid and treating gout.