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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.

Aging is one of the risk factors involved in the development of erectile dysfunction (ED). Growing evidence suggests that oxidative stress is the critical mediator of changes in endothelial function and penile vascular tone in the aging process. Thus, reducing reactive oxygen species (ROS) levels may preserve the bioactivity of the penile vasculature. Antioxidant compounds, such as carvacrol, limit the damage caused by ROS and, therefore, benefit the treatment of ED. Thus, this study aims to evaluate the effects of carvacrol on ED using the D-( +)-galactose aging model. The animals were divided into five groups: control, D-( +)-galactose 150 mg/kg, carvacrol 50 mg/kg or 100 mg/kg, and sildenafil 1.5 mg/kg treated daily for 8 weeks. The physiological, functional, and morphological characteristics of aging-associated ED were evaluated after treatment with carvacrol. Carvacrol prevented ED in a D-( +)-galactose-induced aging model by reducing hypercontractility, enhancing endothelial dysfunction in the rat corpus cavernosum, and improving endothelial health of rat cavernous endothelial cells. In addition, carvacrol prevented the destruction of erectile components essential for penile erection and promoted a reduction of penile tissue senescence, probably through mechanisms that involve the harmful modulation of oxidative stress. Carvacrol significantly improved the erectile function of rats in a D-( +)-galactose-induced aging model and has excellent potential as a new therapeutic alternative in treating erectile dysfunction. Graphical Abstract Mechanisms by which carvacrol prevents age-associated erectile dysfunction induced by D-galactose

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.

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.

Gastric cancer is the fifth most common and fourth type to cause the highest mortality rates worldwide. The leading cause is related to Helicobacter pylori ( H. pylori ) infection. Unfortunately, current treatments have low success rates, highlighting the need for alternative treatments against carcinogenic agents, specifically H. pylori . Noteworthy, natural origin products contain pharmacologically active metabolites such as flavonoids, with potential antimicrobial applications. Objective: This article overviews flavonoid-rich extracts’ biological and pharmacological activities. It focuses on using these substances against Helicobacter pylori infection to prevent gastric cancer. For this, PubMed and Science Direct databases were searched for studies that reported the activity of flavonoids against H. pylori , published within a 10-year time frame (2010 to August 2020). It resulted in 1,773 publications, of which 44 were selected according to the search criteria. The plant family primarily found in publications was Fabaceae (9.61%). Among the flavonoids identified after extraction, the most prevalent were quercetin (19.61%), catechin (13.72), epicatechin (11.76), and rutin (11.76). The potential mechanisms associated with anti- H. pylori activity to the extracts were: inhibition of urease, damage to genetic material, inhibition of protein synthesis, and adhesion of the microorganism to host cells. Conclusion: Plant extracts rich in flavonoids with anti- H. pylori potential proved to be a promising alternative therapy source, reinforcing the relevance of studies with natural products.

Leishmaniasis is a neglected tropical disease caused by Leishmania sp. The therapeutic arsenal is reduced and limited. In this context, acridine derivatives present themselves as promising leishmanicidal compounds. This paper involved synthesizing and evaluating the antileishmanial and immunomodulatory potential of spiro-acridine derivatives. Six spiro-acridine derivatives were obtained through nucleophilic substitution reactions between the acetohydrazide/acetamide intermediates and 9-carbaldehydeacridine, followed by spontaneous cyclization. IR, NMR, and HRMS confirmed the structures. These were analyzed in vitro against L. infantum and L. amazonensis to determine anti-promastigote, anti-amastigote, and cytotoxicity effects. Immunomodulatory activity was evaluated using CBA, DCF-DA, and DAF-FM diacetate. In silico evaluation included molecular docking and dynamics. The spiro-acridines showed a wide range of anti-promastigote activities (IC50 = 0.73–234.95 µM) and non-toxicity to red blood cells. AMTAC-02 and ACMD-03 demonstrated satisfactory anti-amastigote effect (IC50 = 10.47–13.50 µM), low toxicity to macrophages (CC50 = 27.22–569.50 µM), and cytokine and reactive species modulation. Molecular docking proposed cysteine protease B of L. amazonensis as a target, and molecular dynamics analysis highlighted the complex’s stability using RMSD, Rg, SASA, DCCM, PCA, and MM-PBSA (ΔG = −65.225 kJ/mol). Furthermore, QM-MM calculation provided the best energy for ACMD-03 (−199.30 au). Hence, AMTAC-02 and ACMD-03 demonstrated antileishmanial potential, making them promising entities for the development of leishmanicidal drug candidates.

The present study proposed the synthesis of a novel acridine derivative not yet described in the literature, chemical characterization by NMR, MS, and IR, followed by investigations of its antileishmanial potential. In vitro assays were performed to assess its antileishmanial activity against L. amazonensis strains and cytotoxicity against macrophages through MTT assay and annexin V-FITC/PI, and the ability to perform an immunomodulatory action using CBA. To investigate possible molecular targets, its interaction with DNA in vitro and in silico targets were evaluated. As results, the compound showed good antileishmanial activity, with IC50 of 6.57 (amastigotes) and 94.97 (promastigotes) µg mL−1, associated with non-cytotoxicity to macrophages (CC50 > 256.00 µg mL−1). When assessed by flow cytometry, 99.8% of macrophages remained viable. The compound induced an antileishmanial effect in infected macrophages and altered TNF-α, IL-10 and IL-6 expression, suggesting a slight immunomodulatory activity. DNA assay showed an interaction with the minor grooves due to the hyperchromic effect of 47.53% and Kb 1.17 × 106 M−1, and was sustained by docking studies. Molecular dynamics simulations and MM-PBSA calculations propose cysteine protease B as a possible target. Therefore, this study demonstrates that the new compound is a promising molecule and contributes as a model for future works.