Sharif Hina, Akash Muhammad Sajid Hamid, Rehman Kanwal, Irshad Kanwal, Imran Imran
Department of Pharmaceutical Chemistry, Government College University, Faisalabad, Pakistan.
Department of Pharmacy, University of Agriculture, Faisalabad, Pakistan.
J Food Biochem. 2020 Nov;44(11):e13449. doi: 10.1111/jfbc.13449. Epub 2020 Aug 27.
Under physiological conditions, endothelial cells act as protective barrier which prevents direct contact of blood with circulating factors via production of tissue plasminogen activator. Risk factors of metabolic disorders are responsible to induce endothelial dysfunction and may consequently lead to prognosis of atherosclerosis. This article summarizes the process of atherosclerosis which involves number of sequences including formation and interaction of AGE-RAGE, activation of polyol pathway, protein kinase C, and hexosamine-mediated pathway. All these mechanisms can lead to the development of oxidative stress which may further aggravate condition. Different pharmacological interventions are being used to treat atherosclerosis, however, these might be associated with mild to severe side effects. Therefore, plant-based bioactive compounds having potential to combat and prevent atherosclerosis in diabetic patients are attaining recent focus. By understanding process of development and mechanisms involved in atherosclerotic plaque formation, these bioactive compounds can be better option for future therapeutic interventions for atherosclerosis treatment. PRACTICAL APPLICATIONS: Atherosclerosis is one of major underlying disorders of cardiovascular diseases which occur through multiple mechanisms and is associated with metabolic disorders. Conventional therapeutic interventions are not only used to treat atherosclerosis, but are also commonly associated with mild to severe side effects. Therefore, nowadays, bioactive compounds having potential to combat and prevent atherosclerosis in diabetic patients are preferred. By understanding mechanisms involved in atherosclerotic plaque formation, bioactive compounds can be better understood for treatment of atherosclerosis. In this manuscript, we have focused on treatment strategies of atherosclerosis using bioactive compounds notably alkaloids and flavonoids having diverse pharmacological and therapeutic potentials with special focus on the mechanism of action of these bioactive compounds suitable for treatment of atherosclerosis. This manuscript will provide the scientific insights of bioactive compounds to researchers who are working in the area of drug discovery and development to control pathogenesis and development of atherosclerosis and its associated cardiometabolic disorders.
在生理条件下，内皮细胞作为一种保护屏障，通过产生组织纤溶酶原激活物来防止血液与循环因子直接接触。代谢紊乱的危险因素会导致内皮功能障碍，进而可能导致动脉粥样硬化的预后不良。本文总结了动脉粥样硬化的过程，该过程涉及多个环节，包括晚期糖基化终末产物（AGE）-受体（RAGE）的形成与相互作用、多元醇途径的激活、蛋白激酶C以及己糖胺介导的途径。所有这些机制都可能导致氧化应激的发生，进而使病情进一步加重。目前正在使用不同的药物干预措施来治疗动脉粥样硬化，然而，这些措施可能会伴有轻至重度的副作用。因此，具有对抗和预防糖尿病患者动脉粥样硬化潜力的植物源生物活性化合物近来备受关注。通过了解动脉粥样硬化斑块形成的发展过程和相关机制，这些生物活性化合物可能成为未来治疗动脉粥样硬化的更好选择。实际应用：动脉粥样硬化是心血管疾病的主要潜在病症之一，其通过多种机制发生，且与代谢紊乱相关。传统的治疗干预措施不仅用于治疗动脉粥样硬化，还通常伴有轻至重度的副作用。因此，如今具有对抗和预防糖尿病患者动脉粥样硬化潜力的生物活性化合物更受青睐。通过了解动脉粥样硬化斑块形成的相关机制，可以更好地理解生物活性化合物在治疗动脉粥样硬化方面的作用。在本手稿中，我们重点关注了使用生物活性化合物（特别是具有多种药理和治疗潜力的生物碱和黄酮类化合物）治疗动脉粥样硬化的策略，并特别关注了这些生物活性化合物适用于治疗动脉粥样硬化的作用机制。本手稿将为从事药物研发领域以控制动脉粥样硬化及其相关心脏代谢紊乱的发病机制和发展的研究人员提供生物活性化合物的科学见解。
