Imine Derivatives of Benzoxazole Attenuate High-Fat Diet-Induced Hyperlipidemia by Modulation of Lipid-Regulating Genes

作者：Maryam Zaib, Muhammad Nasir Hayat Malik, Ramla Shabbir, Muhammad Naveed Mushtaq, Waqas Younis, Shah Jahan, Ishtiaq Ahmed, Hafiz Aamir Ali Kharl · 发表于：ACS Omega · 年份：2023 · DOI：10.1021/acsomega.3c00443 · 被引用次数：5 · 研究领域：Computational Drug Discovery Methods、Biochemical Acid Research Studies、Pharmacogenetics and Drug Metabolism

High Resolution Image Download MS PowerPoint Slide Purpose: Hyperlipidemia being the prominent risk factor of cardiovascular diseases and side effects associated with the current lipid-lowering drugs have attracted the interest of scientists in the quest for new alternatives. In view of the diverse pharmacological potentials of benzoxazole (BZX) compounds, this study was designed to evaluate the antihyperlipidemic activity of imine derivatives of BZX in high-fat diet (HFD)-fed rats. Methods: Hyperlipidemia was induced in Sprague–Dawley rats by using HFD for 28 days. On the 28th day, blood samples were collected, and animals having serum triglycerides (TG) greater than 400 mg/dL and total cholesterol (TC) greater than 280 mg/dL were selected for further study. Hyperlipidemic rats were daily treated with either a vehicle or simvastatin (SIM; 20 mg/kg) or BZX compounds (10, 20, and 30 mg/kg), for 12 consecutive days. After the specified time duration, hyperlipidemic biomarkers were evaluated in the blood samples of sacrificed rats. Liver samples were collected for histopathological and mRNA analyses. Binding affinities of BZX derivatives with different targets were assessed by molecular docking. Results: The present study revealed that the BZX derivatives dose-dependently reduced the serum levels of TC, TG, low-density lipoprotein, and very low-density lipoprotein along with improvement in high-density lipoprotein levels. Similarly, all the compounds reduced HFD-induced alanine ...