血脂灵片对脂肪酸合酶的体外抑制作用

Inhibition of Fatty Acid Synthase in vitro by Xuezhiling Tablets

摘要:

目的: 研究血脂灵片对脂肪酸合酶(fatty acid synthase,FAS)的体外抑制作用,并初步探索其作用机制。 方法: 以乙酰辅酶A(AcCoA),丙二酰辅酶A(MalCoA),乙酰乙酰辅酶A(AcAcCoA),乙酰乙酸乙酯,丁烯酸乙酯,原型辅酶Ⅱ(NADPH)等为底物,采用紫外分光光度法,通过测定340 nm下NADPH吸光度值的变化进行FAS活性测定,研究不同剂量血脂灵片对FAS全反应及不同活性中心的体外抑制作用。 结果: 血脂灵片对FAS具有抑制作用,给药浓度达到150 mg·L^-1时,能够抑制51%的酶活性,且对FAS的抑制具有剂量和时间依赖关系。对于FAS的不同活性中心,血脂灵片作用不同,其对烯酰还原反应和AcAcCoA还原反应的抑制稍强于酮酰还原反应,随着给药浓度的增加,对各活性中心的抑制能力逐渐增强,当给药浓度达到150 mg·L^-1时,各个活性中心剩余活性均小于70%,但仍保留有50%以上的剩余活性。 结论: 血脂灵片对FAS具有一定的抑制作用,且对FAS的抑制是通过作用于多个位点实现的。实验为血脂灵片降血脂作用与靶点FAS有关的推断提供了实验依据,并为血脂灵片应用于肥胖症等FAS靶点相关疾病提供了参考。

Abstract:

Objective:To study the inhibition of fatty acid synthase (FAS) by Xuezhiling tablets in vitro, and explore its mechanism of action. Method: The ultraviolet spectroscopy was used to evaluate the activity of FAS through monitoring the alteration of absorbance(A) value of reduced nicotinamide-adenine dinucleotide phosphate(NADPH) and the substrates were respectively acetyl coenzyme A(AcCoA), malonyl-CoA(MalCoA), acetoacetyl-coenzymeA(AcAcCoA), ethyl acetoacetate, ethyl crotonate, NADPH for different active sites. The inhibition of FAS by overall reduction and different active sites was separately detected after the treatment with different doses of Xuezhiling tablets. Result: The activity of FAS could be inhibited by Xuezhiling tablets. After the treatment with Xuezhiling tablets (150 mg·L^-1), the inhibition ratio was 51% with manner if time and dose relationship. For the different active sites of FAS, Xuezhiling tablets displayed different abilities. It showed more potential in inhibiting the enoyl reduction and AcAcCoA reduction than keto-acyl reduction, and it was also dose dependent for the different active sites. The residual activity of different active sites was less than 70%,and more than 50%, when FAS was treated with Xuezhiling tablets at the concentration of 150 mg·L^-1. Conclusion: FAS can be inhibited by Xuezhiling tablets, and this ability was attributed to inhibit the different active sites of FAS. This article prove that the ratiocination about the lowering blood lipids of Xuezhiling tablets is related to FAS and it can be a reference for Xuezhiling tablets used for obesity and other disease that related to FAS.