The global population above 60 years has been growing exponentially in the last decades, which is accompanied by an increase in the prevalence of age-related chronic diseases, highlighting cardiovascular diseases (CVDs), such as hypertension, atherosclerosis, and heart failure. Aging is the main risk factor for these diseases. Such susceptibility to disease is explained, at least in part, by the increase of oxidative stress, in which it damages cellular components such as proteins, DNA, and lipids. In addition, the chronic inflammatory process in aging “inflammaging” also contributes to cell damage, creating a stressful environment which drives to the development of CVDs. Taken together, it is possible to identify the molecular connection between oxidative stress and the inflammatory process, especially by the crosstalk between the transcription factors Nrf-2 and NF-κB which are mediated by redox signalling and are involved in aging. Therapies that control this process are key targets in the prevention/combat of age-related CVDs. In this review, we show the basics of inflammation and oxidative stress, including the crosstalk between them, and the implications on age-related CVDs.

Carvacrol, a phenolic monoterpene, has diverse biological activities, highlighting its antioxidant and antihypertensive capacity. However, there is little evidence demonstrating its influence on vascular regeneration. Therefore, we evaluated the modulation of carvacrol on endothelial repair induced by endothelial progenitor cells (EPC) in hypertension. Twelve-week-old spontaneously hypertensive rats (SHR) were treated with a vehicle, carvacrol (50 or 100 mg/kg/day), or resveratrol (10 mg/kg/day) orally for four weeks. Wistar Kyoto (WKY) rats were used as the normotensive controls. Their systolic blood pressure (SBP) was measured weekly through the tail cuff. The EPCs were isolated from the bone marrow and peripherical circulation and were quantified by flow cytometry. The functionality of the EPC was evaluated after cultivation through the quantification of colony-forming units (CFU), evaluation of eNOS, intracellular detection of reactive oxygen species (ROS), and evaluation of senescence. The superior mesenteric artery was isolated to evaluate the quantification of ROS, CD34, and CD31. Treatment with carvacrol induced EPC migration, increased CFU formation and eNOS expression and activity, and reduced ROS and senescence. In addition, carvacrol reduced vascular ROS and increased CD31 and CD34 expression. This study showed that treatment with carvacrol improved the functionality of EPC, contributing to the reduction of endothelial dysfunction.

Cardiovascular diseases are the primary cause of morbidity and mortality worldwide. The function and structure of blood vessels play a crucial role in the development and aggravation of these diseases. Natural products, such as aromatic plants, present a wide variety of terpenes content. Monoterpenes, a selected group of terpenes, have two building blocks of five-carbon isoprene (C₅H₈) unit. Moreover, different monoterpenes have shown pharmacological activity in the cardiovascular system, particularly in vascular function, which is mediated, at least in part, by modulating the nitric oxide pathway, oxidative stress, inflammation, and calcium signaling. Therefore, this review addresses the role of monoterpenes as pharmacological tools in the vascular system, providing mechanisms of action and their biological effects.

Carvacrol is a monoterpene found in essential oils from various plants. Several pharmacological properties have already been described for carvacrol, including antimicrobial, anti-inflammatory, anticarcinogenic, antioxidant, vasorelaxant and hypotensive activities. The present study evaluated the effect of carvacrol on hypertensive rats with erectile dysfunction. Twelve-week-old spontaneously hypertensive rats (SHR) were treated with vehicle, carvacrol (50 or 100 mg/kg/day) or sildenafil (1.5 mg/kg/day), intragastrically, for four weeks. Wistar Kyoto (WKY) rats were used as the normotensive controls. All substances tested reduced systolic blood pressure during the treatment period. The intracavernosal pressure/mean arterial pressure ratio of the hypertensive rats was improved by carvacrol and sildenafil treatments. In isolated rat corpora cavernosa, the acetylcholine- and SNP-induced relaxation responses were significantly increased by carvacrol or sildenafil treatments. In SHR corpora cavernosa, treatment with carvacrol attenuated the hypercontractility induced by phenylephrine or electrical field stimulation. Phe-induced hypercontractility in the presence of tempol was not altered when compared to the response induced by carvacrol alone. In rat corpora cavernosa fluorescence intensity emitted by the DHE probe was significantly reduced in SHR treated (carvacrol or sildenafil) groups when compared to that emitted in the SHR-CTL. This study showed that carvacrol improves the erectile function of hypertensive rats and reduces endothelial dysfunction, smooth muscle cell hypercontractility and superoxide anion generation.

Aging is a major risk factor for chronic diseases, including cardiovascular diseases. Endothelial cells (ECs) are particularly vulnerable to age-related stress, and endothelial senescence contributes to vascular aging. In the present study, we applied a triple-screening strategy to identify terpenes that modulate senescence-associated phenotypes in endothelial cells. Rat aortic endothelial cells (RAECs) were exposed to D-galactose to induce a senescence-associated phenotype, and 20 g/L was selected for subsequent experiments. Subsequently, twenty terpenes were tested at four concentrations (10⁻⁹, 10⁻⁸, 10⁻⁷, and 10⁻⁶ mol/L) using three phenotypic readouts: senescence-associated β-galactosidase (SA-β-Gal) activity, cell viability, and oxidative stress. The screening identified multiple terpenes that reduced SA-β-Gal activity and oxidative stress, while five compounds improved cell viability under D-galactose conditions. Among them, citral, terpinolene, and farnesol were the only compounds that showed concordant beneficial effects across the three screening endpoints at the same concentration. In addition, 1R-(-)-myrtenol and trans-caryophyllene showed lower SA-β-Gal activity and preferentially reduced cell viability in D-galactose-treated cells, warranting follow-up studies to determine whether they exhibit senolytic activity. Overall, these findings identify terpene candidates that modulate senescence-associated phenotypes in ECs and support further mechanistic studies to define their senescence-related actions and potential relevance for natural-product-based strategies targeting EC dysfunction.