Role of Terpenophenolics in Modulating Inflammation and Apoptosis in Cardiovascular Diseases: A Review

Abstract

One in every three deaths worldwide is caused by cardiovascular diseases (CVDs), estimating a total of 17.9 million deaths annually. By 2030, it is expected that more than 24 million people will die from CVDs related complications. The most common CVDs are coronary heart disease, myocardial infarction, stroke, and hypertension. A plethora of studies has shown inflammation causing both short-term and long-term damage to the tissues in many organ systems, including the cardiovascular system. In parallel to inflammation processes, it has been discovered that apoptosis, a mode of programmed cell death, may also contribute to CVD development due to the loss of cardiomyocytes. Terpenophenolic compounds are comprised of terpenes and natural phenols as secondary metabolites by plants and are commonly found in the genus Humulus and Cannabis. A growing body of evidence has shown that terpenophenolic compounds exhibit protective properties against inflammation and apoptosis within the cardiovascular system. This review highlights the current evidence elucidating the molecular actions of terpenophenolic compounds in protecting the cardiovascular system, i.e., bakuchiol, ferruginol, carnosic acid, carnosol, carvacrol, thymol and hinokitiol. The potential of these compounds is discussed as the new nutraceutical drugs that may help to decrease the burden of cardiovascular disorders.

Keywords: apoptosis; atherosclerosis; cardiovascular diseases (CVDs); inflammation; oxidative stress; phenolics; terpenes; terpenophenolics.

Figure 1

Summary of the signalling pathways involved in the development of heart failure. Hyperlipidemia, hypertension, and hyperglycemia trigger the generation of reactive oxygen species (ROS), which induces oxidative stress in the cardiomyocytes. ROS also induces inflammation responses and cell apoptosis mediated by the mitogen-activated protein kinase (MAPK) pathway. As a compensation mechanism to maintain the structural integrity of the heart, apoptotic cardiomyocytes were degraded and then replaced by myocardial fibrosis. On the contrary, the alteration in the architecture of the heart creates malfunction in both the systolic and diastolic flows, ultimately resulting in heart failure.

Figure 2

Chemical structures of the terpenophenolic compounds with potential to be used in the development of novel medications to treat cardiovascular diseases.

Figure 3

Terpenophenolic compounds exert their potential in attenuating the development of heart failure owing to their ability to counteract reactive oxygen species, oxidative stress, inflammation, apoptosis, and fibrosis via several molecular pathways.