茯苓叶降低高脂血症大鼠血脂异常和氧化应激及其潜在靶点的研究

D. E. Uti, U. Ibiam, W. A. Omang, P. A. Udeozor, G. Umoru, S. Nwadum, Inalegwu Bawa, E. Alum, J. Mordi, E. O. Okoro, U. Obeten, Eucharia N. Onwe, S. Zakari, Ohunene Rukayat Opotu, P. M. Aja
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引用次数: 3

摘要

摘要本研究旨在探讨降血脂药Buchholzia coriacea (BCE)溶剂提取物对高脂血症的治疗作用,并鉴定其潜在的生物活性成分。以Wistar白化病大鼠为研究对象,将其分为7组:正常对照组,正常大鼠400mg /kg.b。BCE (NRG组)、高脂血症对照组(HPC组)、标准对照药物阿托伐他汀(SC组)以及200、400和800 mg/kg.b的高脂血症大鼠。分别为T1、T2、T3组。通过与乙酰辅酶a羧化酶(ACC)和脂肪酸合成酶(FASN)的硅结合分析了BCE提取物中可能具有功能的化合物。通过虚拟筛选、吸收分布、代谢排泄和毒性预测分析,确定了化合物的结合亲和力和药物样性质。通过气相色谱-质谱联用分析,鉴定出了BCE叶提取物中含有生物碱、皂苷、黄酮类、酚类、萜类等44种化合物。与HPC组相比,BCE显著降低了三酰甘油、总胆固醇、低密度脂蛋白、极低密度脂蛋白、动脉粥样硬化系数、动脉粥样硬化指数和冠状动脉危险指数水平,同时提高了高密度脂蛋白水平和心脏保护指数。BCE降低了丙二醛的含量,丙二醛在HPC中表现出很高的水平。超氧化物歧化酶和谷胱甘肽过氧化物酶活性以及谷胱甘肽水平在BCE处理后增加,否则HPC会降低。在已鉴定的BCE化合物中,lupenone和2,7-二甲基萘对ACC和FASN的结合亲和力最高,表明这两种化合物可能是具有降脂特性的生物活性BCE成分。研究发现,BCE可通过调节血脂、保护心血管功能、抑制氧化应激等方式抑制高脂血症。BCE可能是探索治疗血脂异常新药的天然来源。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Buchholzia coriacea Leaves Attenuated Dyslipidemia and Oxidative Stress in Hyperlipidemic Rats and Its Potential Targets In Silico
Abstract The study aimed to investigate how the solvent extract of Buchholzia coriacea (BCE), a widely known hypolipidemic agent, could contribute to hyperlipidemia treatment and identify the potential bioactive compounds. We studied Wistar albino rats, dividing them into seven groups: the normal control, normal rats treated with 400 mg/kg.b.wt of BCE (NRG group), the hyperlipidemic control (HPC group), hyperlipidemic rats treated with atorvastatin, a standard control drug (SC group), as well as 200, 400, and 800 mg/kg.b.wt of BCE extract respectively (T1, T2, T3 groups). The potential compounds that functioned in BCE extract were analyzed by in silico binding to acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN). The binding affinities and drug-like properties of the compounds were determined using virtual screening and absorption distribution metabolism excretion and toxicity prediction analysis. The gas chromatography-mass spectrometry analysis identified alkaloids, saponins, flavonoids, phenols, terpenoids, and 44 chemical compounds in the leaf extract of BCE. BCE significantly reduced the levels of triacylglycerol, total cholesterol, low-density lipoprotein, very low-density lipoprotein, atherogenic coefficient, atherogenic index, and coronary risk index, while enhancing the levels of high-density lipoprotein and cardioprotective index in comparison to the HPC group. The BCE reduced malondialdehyde quantities, which exhibit high levels in HPC. Superoxide dismutase and glutathione peroxidase activities as well as glutathione levels, which are otherwise reduced in HPC, were increased upon the BCE treatment. Among the identified BCE compounds, lupenone and 2,7-dimethylnaphthalene exhibited the highest binding affinities to ACC and FASN, suggesting that these two compounds might be the bioactive BCE components displaying hypolipidemic properties. BCE is found to be beneficial in blocking hyperlipidemia through the modulation of lipid profile, the protection of cardiovascular function, as well as the suppression of oxidative stress. BCE may be a natural source for exploring novel drugs for the treatment of dyslipidemia.
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