Erectile dysfunction (ED) is defined as the inability to achieve and/or maintain penile erection sufficient for satisfactory sexual relations, and aging is one of the main risk factors involved. The D-(+)-Galactose aging model is a consolidated methodology for studies of cardiovascular aging; however, its potential for use with ED remain unexplored. The present study proposed to characterize a new experimental model for ED, using the D-(+)-Galactose aging model. For the experiments, the animals were randomly divided into three groups receiving: vehicle (CTL), D-galactose 150 mg/kg (DGAL), and D-(+)-galactose 150 mg/Kg + sildenafil 1.5 mg/Kg (DGAL+SD1.5) being administered daily for a period of eight weeks. All of the experimental protocols were previously approved by the Ethics Committee on the Use of Animals at the Federal University of Paraíba n° 9706070319. During the treatment, we analyzed physical, molecular, and physiological aspects related to the aging process and implicated in the development of ED. Our findings demonstrate for the first time that D-(+)-Galactose-induced aging represents a suitable experimental model for ED assessment. This was evidenced by an observed hyper-contractility in corpora cavernosa, significant endothelial dysfunction, increased ROS levels, an increase in cavernous tissue senescence, and the loss of essential penile erectile components.

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.

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.