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Chronic venous disease (CVD) is a prevalent condition in adults, significantly affecting the global elderly population, with a higher incidence in women than in men. The modulation of gene expression through microRNA (miRNA) partly regulated the development of cardiovascular disease (CVD). Previous research identified a functional analysis of seven genes (CDS2, HDAC5, PPP6R2, PRRC2B, TBC1D22A, WNK1, and PABPC3) as targets of miRNAs related to CVD. In this context, miRNAs emerge as essential candidates for CVD diagnosis, representing novel molecular and biological knowledge. This work aims to identify, by network analysis, the miRNAs involved in CVD as potential biomarkers, either by interacting with small molecules such as toxins and pollutants or by searching for new drugs. Our study shows an updated landscape of the signaling pathways involving miRNAs in CVD pathology. This latest research includes data found through experimental tests and uses predictions to propose both miRNAs and genes as potential biomarkers to develop diagnostic and therapeutic methods for the early detection of CVD in the clinical setting. In addition, our pharmacological network analysis has, for the first time, shown how to use these potential biomarkers to find small molecules that may regulate them. Between the small molecules in this research, toxins, pollutants, and drugs showed outstanding interactions with these miRNAs. One of them, hesperidin, a widely prescribed drug for treating CVD and modulating the gene expression associated with CVD, was used as a reference for searching for new molecules that may interact with miRNAs involved in CVD. Among the drugs that exhibit the same miRNA expression profile as hesperidin, potential candidates include desoximetasone, curcumin, flurandrenolide, trifluridine, fludrocortisone, diflorasone, gemcitabine, floxuridine, and reversine. Further investigation of these drugs is essential to improve the treatment of cardiovascular disease. Additionally, supporting the clinical use of miRNAs as biomarkers for diagnosing and predicting CVD is crucial.

Peripheral venous hypertension has emerged as a prominent characteristic of venous disease (VD). This disease causes lower limb edema due to impaired blood transport in the veins. The phlebotonic drugs in use showed moderate evidence for reducing edema slightly in the lower legs and little or no difference in the quality of life. To enhance the probability of favorable experimental results, a virtual screening procedure was employed to identify molecules with potential therapeutic activity in VD. Compounds obtained from multiple databases, namely AC Discovery, NuBBE, BIOFACQUIM, and InflamNat, were compared with reference compounds. The examination of structural similarity, targets, and signaling pathways in venous diseases allows for the identification of compounds with potential usefulness in VD. The computational tools employed were rcdk and chemminer from R-Studio and Cytoscape. An extended fingerprint analysis allowed us to obtain 1846 from 41,655 compounds compiled. Only 229 compounds showed pharmacological targets in the PubChem server, of which 84 molecules interacted with the VD network. Because of their descriptors and multi-target capacity, only 18 molecules of 84 were identified as potential candidates for experimental evaluation. We opted to evaluate the berberine compound because of its affordability, and extensive literature support. The experiment showed the proposed activity in an acute venous hypertension model.

Chiranthodendron pentadactylon Larreat is a tree native to southeastern Mexico and Guatemala. Its flower is used in Mexican folk medicine to treat a variety of diseases, including conditions of blood pressure. However, scientific information on its usefulness in this pathology is lacking. The present study evaluates the effect of a methanolic extract (ME) from the flower and its active constituents on heart rate (HR) and mean arterial pressure (MAP) in anesthetized rats (MAPHR). The study also analyzed the effects on rat-isolated aortic rings (RIAR) and the rat mesenteric arterial bed (MABR). Active fractions were chromatographed, which led to the isolation of cyanidin 3- O -glucoside (C3G) identified through HPLC. The Chiranthodendron pentadactylon flowers produced hypotensive and vasorelaxant effects associated with C3G. The vasorelaxant effect is a mechanism underlying the synthesis and release of nitric oxide (NO). Neither cholinergic receptors nor prostaglandins are involved. ME and C3G cause cardiovascular depression in anesthetized rats via cholinergic and prostanoid mechanisms. Our research expands the scientific understanding of the flowers on the rat cardiovascular system. This amplifies the appreciation of the flower's ethnomedicine employed to control blood pressure. However, researchers need to conduct toxicity studies to determine the safety of this plant.

Many natural products have been acquired from plants for their helpful properties. Medicinal plants are used for treating a variety of pathologies or symptoms. The axes of many pathological processes are inflammation, oxidative stress, and senescence. This work is focused on identifying Mexican medicinal plants with potential anti-oxidant, anti-inflammatory, anti-aging, and anti-senescence effects through network analysis and chemoinformatic screening of their phytochemicals. We used computational methods to analyze drug-like phytochemicals in Mexican medicinal plants, multi-target compounds, and signaling pathways related to anti-oxidant, anti-inflammatory, anti-aging, and anti-senescence mechanisms. A total of 1373 phytochemicals are found in 1025 Mexican medicinal plants, and 148 compounds showed no harmful functionalities. These compounds displayed comparable structures with reference molecules. Based on their capacity to interact with pharmacological targets, three clusters of Mexican medicinal plants have been established. Curatella americana , Ximenia americana , Malvastrum coromandelianum , and Manilkara zapota all have anti-oxidant, anti-inflammatory, anti-aging, and anti-senescence effects. Plumeria rubra , Lonchocarpus yucatanensis , and Salvia polystachya contained phytochemicals with anti-oxidant, anti-inflammatory, anti-aging, and anti-senescence reported activity. Lonchocarpus guatemalensis , Vallesia glabra , Erythrina oaxacana , and Erythrina sousae have drug-like phytochemicals with potential anti-oxidant, anti-inflammatory, anti-aging, and anti-senescence effects. Between the drug-like phytochemicals, lonchocarpin, vallesine, and erysotrine exhibit potential anti-oxidant, anti-inflammatory, anti-aging, and anti-senescence effects. For the first time, we conducted an initial virtual screening of selected Mexican medicinal plants, which was subsequently confirmed in vivo, evaluating the anti-inflammatory activity of Lonchocarpus guatemalensis Benth in mice.