Islam Muhammad Shahidul, Sharif Anjiya, Kwan Nathania, Tam Kam C
Department of Chemical Engineering, Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada.
Mol Pharm. 2022 May 2;19(5):1248-1272. doi: 10.1021/acs.molpharmaceut.2c00007. Epub 2022 Mar 25.
Bile acids, the endogenous steroid nucleus containing signaling molecules, are responsible for the regulation of multiple metabolic processes, including lipoprotein and glucose metabolism to maintain homeostasis. Within our body, they are directly produced from their immediate precursors, cholesterol C (low-density lipoprotein C, LDL-C), through the enzymatic catabolic process mediated by 7-α-hydroxylase (CYP7A1). Bile acid sequestrants (BASs) or amphiphilic resins that are nonabsorbable to the human body (being complex high molecular weight polymers/electrolytes) are one of the classes of drugs used to treat hypercholesterolemia (a high plasma cholesterol level) or dyslipidemia (lipid abnormalities in the body); thus, they have been used clinically for more than 50 years with strong safety profiles as demonstrated by the Lipid Research Council-Cardiovascular Primary Prevention Trial (LRC-CPPT). They reduce plasma LDL-C and can slightly increase high-density lipoprotein C (HDL-C) levels, whereas many of the recent clinical studies have demonstrated that they can reduce glucose levels in patients with type 2 diabetes mellitus (T2DM). However, due to higher daily dosage requirements, lower efficacy in LDL-C reduction, and concomitant drug malabsorption, research to develop an "ideal" BAS from sustainable or natural sources with better LDL-C lowering efficacy and glucose regulations and lower side effects is being pursued. This Review discusses some recent developments and their corresponding efficacies as bile removal or LDL-C reduction of natural biopolymer (polysaccharide)-based compounds.
胆汁酸是含有信号分子的内源性甾体核，负责调节多种代谢过程，包括脂蛋白和葡萄糖代谢以维持体内平衡。在我们体内，它们由其直接前体胆固醇C（低密度脂蛋白C，LDL-C）通过7-α-羟化酶（CYP7A1）介导的酶促分解代谢过程直接产生。胆汁酸螯合剂（BASs）或人体不可吸收的两亲性树脂（为高分子量聚合物/电解质复合物）是用于治疗高胆固醇血症（高血浆胆固醇水平）或血脂异常（体内脂质异常）的一类药物；因此，它们已在临床上使用了50多年，如脂质研究委员会 - 心血管病一级预防试验（LRC-CPPT）所示，具有很强的安全性。它们可降低血浆LDL-C，并可略微提高高密度脂蛋白C（HDL-C）水平，而最近的许多临床研究表明，它们可降低2型糖尿病（T2DM）患者的血糖水平。然而，由于每日剂量要求较高、降低LDL-C的疗效较低以及伴随的药物吸收不良，人们正在开展研究，以从可持续或天然来源开发一种“理想”的BAS，其具有更好的降低LDL-C疗效和血糖调节作用以及更低的副作用。本综述讨论了基于天然生物聚合物（多糖）的化合物在胆汁清除或降低LDL-C方面的一些最新进展及其相应疗效。
