The Role of Punicalagin and Its Metabolites in Atherosclerosis and Risk Factors Associated with the Disease

Abstract

Atherosclerotic cardiovascular disease (ACVD) is the leading cause of death worldwide. Although current therapies, such as statins, have led to a marked reduction in morbidity and mortality from ACVD, they are associated with considerable residual risk for the disease together with various adverse side effects. Natural compounds are generally well-tolerated; a major recent goal has been to harness their full potential in the prevention and treatment of ACVD, either alone or together with existing pharmacotherapies. Punicalagin (PC) is the main polyphenol present in pomegranates and pomegranate juice and demonstrates many beneficial actions, including anti-inflammatory, antioxidant, and anti-atherogenic properties. The objective of this review is to inform on our current understanding of the pathogenesis of ACVD and the potential mechanisms underlying the beneficial actions of PC and its metabolites in the disease, including the attenuation of dyslipidemia, oxidative stress, endothelial cell dysfunction, foam cell formation, and inflammation mediated by cytokines and immune cells together with the regulation of proliferation and migration of vascular smooth muscle cells. Some of the anti-inflammatory and antioxidant properties of PC and its metabolites are due to their strong radical-scavenging activities. PC and its metabolites also inhibit the risk factors of atherosclerosis, including hyperlipidemia, diabetes mellitus, inflammation, hypertension, obesity, and non-alcoholic fatty liver disease. Despite the promising findings that have emerged from numerous in vitro, in vivo, and clinical studies, deeper mechanistic insights and large clinical trials are required to harness the full potential of PC and its metabolites in the prevention and treatment of ACVD.

Pomegranate Extract Administration Reverses Loss of Motor Coordination and Prevents Oxidative Stress in Cerebellum of Aging Mice

“…The main active compounds of our pomegranate extract (see Table S1) are polyphenols and punicalagins. Many articles show that punicalagin has different biological activities, such as in cancer, cardiovascular diseases, liver diseases, and inflammation [60][61][62][63]. Recently, a pharmacological study found that this substance and its polyphenols had significant neuroprotective potential against Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and chronic mild stress [20,23,25,64,65].…”

The association between vitamin K intake and dyslipidemia in US adults: the mediating effect of insulin resistance

“…Dyslipidemia is one of the most common chronic diseases, which is characterized by elevated total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), as well as depressed high-density lipoprotein cholesterol (HDL-C). 1 The accumulation of cholesterol triggers a stress response, leading to apoptotic necrosis and the gradual formation of stable atherosclerotic lesions, ultimately resulting in the development of cardiovascular disease (CVD), 2 which is the most common clinical consequence of dyslipidemia. 3 Environmental (such as poor dietary habits, 4 and poor lifestyle such as smoking and drinking 5 ) and genetic factors are important risk factors in the development of dyslipidemia.…”