Monoterpenes and their derivatives as agents for cardiovascular disease management: A systematic review and meta-analysis

Monoterpenes are one of the most studied plant's secondary metabolites, they are found abundantly in essential oils of aromatic plants. They also have a great range of pharmacological properties, such as antihypertensive, bradycardic, antiarrhythmic and hypotensive. In the face of the burden caused by cardiovascular disease (CVDs) worldwide, studies using monoterpenes to assess their cardiovascular effects have increased over the years. This systematic review aimed to summarize the use of monoterpenes in animal models of any CVDs. PubMed, SCOPUS, LILACS and Web of Science databases were used to search for articles that used monoterpenes, in any type of administration, to treat or prevent CVDs in animal models. The PRISMA guidelines were followed. Two independent researchers extracted main characteristics of studies, methods and outcomes. Data obtained were analyzed qualitatively and quantitatively. At the ending of the search process, 33 articles were selected for the systematic review. Of these, 17 articles were included in the meta-analysis. A total of 16 different monoterpenes were found for the treatment of hypertension, myocardial infarction, pulmonary hypertension, cardiac hypertrophy and arrhythmia. The main actions include hypotension, bradycardia, vasodilatation, antiarrhythmic, and antioxidant and antiapoptotic properties. From our data, it can be suggested that monoterpenes may be a significant source for new drug development. However, there is still a need to apply these knowledge into clinical research and a long path to pursue before putting them in the market. The variability of cardiovascular effects demonstrated by the monoterpenes highlighted them as a promising candidates for treatment or prevention of CVDs. Nevertheless, studies that investigate their biological sites of action needs to be further encouraged. Main targets of action of monoterpenes in cardiovascular diseases. Red X = inhibition; Up red arrows: upregulation; Down red arrows: downregulation. α-HBDH: alpha-hydroxybutyric dehydrogenase; Akt: protein kinase B; Apaf-1: apoptotic protease-activating factor 1; ASK1-JNK: apoptosis signal-regulating kinase1- c-Jun NH(2)-terminal kinase; BAD: Bcl-2-associated death promoter; Bax: Bcl-2 associated protein X; Bcl-2: B-cell lymphoma protein 2; BNP: brain natriuretic peptide; CAT: catalase; CK: creatine kinase; CK-MB: creatine kinase-MB; cTnT: cardiac troponin levels; Cys: cysteine; eNOS: endothelial nitric oxide synthase; GOT: glutami