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This manuscript presents the numerical optimization (through a mathematical model and an evolutionary algorithm) of the voltage-doubler boost converter, also called the series-capacitor boost converter. The circuit is driven by two transistors, each of them activated according to a switching signal. In the former operation, switching signals have an algebraic dependence from each other. This article proposes a new method to operate the converter. The proposed process reduces the input current ripple without changing any converter model parameter, only the driving signals. In the proposed operation, switching signals of transistors are independent of each other, providing an extra degree of freedom, but on the other hand, this produces an infinite number of possible combinations of duty cycles (the main parameter of switching signals) to achieve the desired voltage gain. In other words, this leads to a problem with infinite possible solutions. The proposed method utilizes an evolutionary algorithm to determine the switching functions and, at the same time, to minimize the input current ripple of the converter. A comparison made between the former and the proposed operation shows that the proposed process achieves a lower input current ripple while achieving the desired voltage gain.

Cholangiocarcinoma (CCA) comprises a group of heterogeneous biliary cancers with dismal prognosis. The etiologies of most CCAs are unknown, but primary sclerosing cholangitis (PSC) is a risk factor. Non-invasive diagnosis of CCA is challenging and accurate biomarkers are lacking. We aimed to characterize the transcriptomic profile of serum and urine extracellular vesicles (EVs) from patients with CCA, PSC, ulcerative colitis (UC), and healthy individuals. Serum and urine EVs were isolated by serial ultracentrifugations and characterized by nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting. EVs transcriptome was determined by Illumina gene expression array [messenger RNAs (mRNA) and non-coding RNAs (ncRNAs)]. Differential RNA profiles were found in serum and urine EVs from patients with CCA compared to control groups (disease and healthy), showing high diagnostic capacity. The comparison of the mRNA profiles of serum or urine EVs from patients with CCA with the transcriptome of tumor tissues from two cohorts of patients, CCA cells in vitro, and CCA cells-derived EVs, identified 105 and 39 commonly-altered transcripts, respectively. Gene ontology analysis indicated that most commonly-altered mRNAs participate in carcinogenic steps. Overall, patients with CCA present specific RNA profiles in EVs mirroring the tumor, and constituting novel promising liquid biopsy biomarkers.

AbstractBackground Millepora alcicornis is a branching hydrocoral common throughout the Caribbean Sea. Like other members of this genus, this species is capable of inducing skin eruptions and blisters with severe pain after contact. In the present study, we investigated the toxicity of theM. alcicornis aqueous extract on several animal models. Considering that some cnidarian hemolysins have been associated to local tissue damage, since they also induce lysis of other cell types, we also made a partial characterization of the hemolytic activity of M. alcicornis aqueous extract. This information is important for understanding the defense mechanisms of the “fire corals”.Methods The effects of pH, temperature, and some divalent cations on the hemolytic activity of the extract were assayed, followed by a zymogram analysis to detect the cytolysins and determine their approximate molecular weight. The toxicity of the aqueous extract was assayed in mice, by intravenous administration, and histopathological changes on several tissues were analyzed by light microscopy. The toxicity of the extract was also tested inArtemia salina nauplii, and the damages caused on the crustaceans were analyzed by transmission and scanning electron microscopy.Results The hemolytic activity of the hydrocoral extract was enhanced in the presence of Ca 2+ (≥2 mM), Mg 2+ (≥6 mM), and Ba2+ (≥0.1 mM); however, it was reduced in the presence of Cu2+(≥0.1 mM), Zn 2+ (≥6 mM), and EDTA (≥0.34 mM). Differences in the pH did not affect the hemolytic activity, but it was temperature-sensitive, since preincubation at ≥ 50 °C sharply reduced hemolysis. The zymogram showed the presence of two types of hemolysins: ~ 28–30 kDa proteins with phospholipase A 2 activity and ~ 200 kDa proteins that do not elicit enzymatic activity. The aqueous extract of this cnidarian was lethal to mice (LD 50 = 17 μg protein/g), and induced kidney, liver, and lung damages. Under denaturing conditions, the aqueous extract completely lost its toxic and hemolytic activities.Conclusions The results showed that the M. alcicornis aqueous extract contains two types of thermolabile hemolysins: proteins of approximately 28–30 kDa with PLA 2 activity, while the others are larger proteins of approximately 200 kDa, which do not possess PLA 2activity. Those thermolabile cytolysins, which are stable to pH changes and whose activity is calcium dependent, are capable of inducing damage in lung, kidney and liver tissues, resulting in a slow death of mice. M. alcicorniscytolysins also provoke tissue dissociation inArtemia salina nauplii that might be attributed to pore forming mechanisms.

Abstract Self-microemulsifying or self-nanoemulsifying drug delivery systems (SMEDDS/SNEDDS) are well known to improve the dissolution and increase the oral bioavailability of hydrophobic drugs, including herbal extracts. Organic extracts of Heliopsis longipes root and affinin, its main component, induce a vasodilator effect; however, they are poorly water soluble and therefore are difficult to administer and dose by the oral route. This research aimed to develop, through pseudo-ternary phase diagrams, a self-microemulsifying system prepared from an ethanolic extract of H. longipes root (HL-SMDS). In addition, the optimized lipid-based formulation was characterized and its in vitro gastrointestinal simulated dissolution was determined. The formulation composed of Transcutol, 55% (solubilizer); Tween80/PG, 10% (surfactant/co-solvent); Labrasol, 35% (surfactant); and the herbal extract was selected as optimal and identified as a SMEDDS, since when coming into contact with water, it forms a micro-emulsion with droplet sizes less than 100 nm. The stability tests showed that HL-SMDS remained stable over time under extreme conditions. Furthermore, the amount of affinin released from HL-SMDS at pH 1 and 6.8 was higher than that of the ethanolic extract from H. longipes root. These results indicate that HL-SMDS is a novel alternative to improve the aqueous solubility and therefore the oral bioavailability of the ethanolic extract of H. longipes root.

Tarantula venoms may be a natural source of new vasodilator components useful in pharmacological research. Moreover, biological function data of the venoms are important to enhance the knowledge about the biodiversity and evolution of these species. The present study aims to describe the vasodilatory activity induced by the venom of Poecilotheria ornata on isolated rat aortic rings. This venom induced a vasodilator activity that was significantly reduced after incubation with L-NAME or ODQ. Measurements of nitrite concentrations on rat aorta homogenates showed that the venom significantly increased the basal levels. Moreover, the venom attenuates the contraction induced by calcium. These results suggest that P. ornata venom contains a mixture of vasodilator components that act through the activation of the nitric oxide/cGMP pathway, as well as, through an endothelium-independent mechanism that involves the calcium influx into vascular smooth muscle cells.

Reef-forming cnidarians are essential for maintaining ecological balance. Unfortunately, coral reefs are endangered due to coral bleaching, which interrupts mutualistic symbiosis between Symbiodiniaceae algae and their coral hosts. Bleaching events result in very high coral mortality and the rapid deterioration of reef structures. Studies aimed at explaining the causes, mechanisms, and consequences of coral bleaching have been mainly conducted with anthozoans, while the impacts of thermal stress responsible for coral bleaching have been scarcely studied in hydrozoans, such as Millepora species (phylum Cnidaria, class Hydrozoa), which are the second most important reef-forming cnidarians. In the present study, the effects of thermal stress caused by the 2015–2016 El Niño on symbiont abundance, exoskeleton structure, and the biochemical composition of Millepora alcicornis were analyzed. Unbleached M. alcicornis specimens exhibited a higher abundance of Breviolum and Durisdinium species, which suggests that unbleached hydrocoral colonies might counteract thermal stress by hosting thermotolerant symbionts of the Durisdinium genus. Bleached hydrocorals exhibited lower levels of calcification than unbleached hydrocorals as well as changes in the microstructure of trabeculae and zooid pores. In contrast, thermal stress did not affect total calcium carbonate and carbohydrate content. Bleached tissues showed significantly higher levels of protein and refractory material, whereas their lipid content decreased considerably. The present study provides evidence that bleached M. alcicornis colonies suffered a decline in calcification and changes in the structure of their exoskeletons after being exposed to the 2015–2016 El Niño. The significant decrease in lipid content suggests that M. alcicornis primarily uses energy stores to maintain vital cellular processes at the expense of calcification.

Venoms from tarantulas contain low molecular weight vasodilatory compounds whose biological action is conceived as part of the envenomation strategy due to its propagative effects. However, some properties of venom-induced vasodilation do not match those described by such compounds, suggesting that other toxins may cooperate with these ones to produce the observed biological effect. Owing to the distribution and function of voltage-gated ion channels in blood vessels, disulfide-rich peptides isolated from venoms of tarantulas could be conceived into potential vasodilatory compounds. However, only two peptides isolated from spider venoms have been investigated so far. This study describes for the first time a subfraction containing inhibitor cystine knot peptides, PrFr-I, obtained from the venom of the tarantula Poecilotheria regalis. This subfraction induced sustained vasodilation in rat aortic rings independent of vascular endothelium and endothelial ion channels. Furthermore, PrFr-I decreased calcium-induced contraction of rat aortic segments and reduced extracellular calcium influx to chromaffin cells by the blockade of L-type voltage-gated calcium channels. This mechanism was unrelated to the activation of potassium channels from vascular smooth muscle, since vasodilation was not affected in the presence of TEA, and PrFr-I did not modify the conductance of the voltage-gated potassium channel Kv10.1. This work proposes a new envenomating function of peptides from venoms of tarantulas, and establishes a new mechanism for venom-induced vasodilation.

The 2015-2016 El Niño-southern oscillation or “ENSO” caused many M. complanata colonies that live in the Mexican Caribbean to experience extensive bleaching. The purpose of this work was to analyze the effect of bleaching on the cellular response of M. complanata, employing a transcriptomic approach with RNA-seq. As expected, bleached specimens contained a significantly lower chlorophyll content than unbleached hydrocorals. The presence of algae of the genera Durusdinium and Cladocopium was only found in tissues of unbleached M. complanata, which could be associated to the greater resistance that these colonies exhibited during bleaching. We found that 299 genes were differentially expressed in M. complanata bleached colonies following the 2015-2016 ENSO in the Mexican Caribbean. The differential expression analysis of bleached M. complanata specimens evidenced enriched terms for functional categories, such as ribosome, RNA polymerase and basal transcription factors, chaperone, oxidoreductase, among others. Our results suggest that the heat-shock response mechanisms displayed by M. complanata include: an up-regulation of endogenous antioxidant defenses; a higher expression of heat stress response genes; up-regulation of transcription-related genes, higher expression of genes associated to transport processes, inter alia. This study constitutes the first differential gene expression analysis of the molecular response of a reef-forming hydrozoan during bleaching.

To date, few studies have been carried out aimed at characterizing the toxins synthesized by hydrocorals of the genus Millepora. The purpose of this study was to explore the toxin diversity and antibacterial activity of the “fire coral” M. complanata using a transcriptomic data mining approach. In addition, the cytolytic and antibacterial activities of the M. complanata nematocyst proteome were experimentally confirmed. Cytolysins were predicted from the transcriptome by comparing against the Animal Toxin Annotation Project database, resulting in 190 putative toxins, including metalloproteases, hemostasis-impairing toxins, phospholipases, among others. The M. complanata nematocyst proteome was analyzed by 1D and 2D electrophoresis and zymography. The zymograms showed different zones of cytolytic activity: two zones of hemolysis at ~25 and ~205 kDa, two regions corresponding to phospholipase A2 (PLA2) activity around 6 and 25 kDa, and a proteolytic zone was observed between 50 and 205 kDa. The hemolytic activity of the proteome was inhibited in the presence of PLA2 and proteases inhibitors, suggesting that PLA2s, trypsin, chymotrypsin, serine-proteases, and matrix metalloproteases are responsible for the hemolysis. On the other hand, antimicrobial peptide sequences were retrieved from their transcripts with the amPEPpy software. This analysis revealed the presence of homologs to SK84, cgUbiquitin, Ubiquicidin, TroTbeta4, SPINK9-v1, and Histone-related antimicrobials in the transcriptome of this cnidarian. Finally, by employing disk diffusion and microdilution assays, we found that the nematocyst peptidome of M. complanata showed inhibitory activity against both Gram-positive and Gram-negative bacteria including S. enteritidis, P. perfectomarina, E. coli, and C. xerosis, among others. This is the first transcriptomic data mining analysis to explore the diversity of the toxins synthesized by an organism of the genus Millepora. Undoubtedly, this work provides information that will broaden our general understanding of the structural richness of cnidarian toxins.

Reef-forming cnidarians are extremely susceptible to the “bleaching” phenomenon caused by global warming. The effect of elevated seawater temperature has been extensively studied on Anthozoans; however, to date the impact of thermal stress on the expression of genes and proteins in Hydrozoan species has not been investigated. The present study aimed to determine the differential proteomic profile of Millepora alcicornis, which inhabits the Mexican Caribbean, in response to the El Niño-Southern Oscillation 2015–2016. Additionally, the cytolytic activity of the soluble proteomes obtained from normal and bleached M. alcicornis was assessed. Bleached specimens showed decreased symbiont’s density and chlorophyll a and c2 levels. After bleaching, we observed a differential expression of 17 key proteins, tentatively identified as related to exocytosis, calcium homeostasis, cytoskeletal organization, and potential toxins, including a metalloprotease, a phospholipase A2 (PLA2), and an actitoxin. Although, some of the differentially expressed proteins included potential toxins, the hemolytic, PLA2, and proteolytic activities elicited by the soluble proteomes from bleached and normal specimens were not significantly different. The present study provides heretofore-unknown evidence that thermal stress produces a differential expression of proteins involved in essential cellular processes of Hydrozoan species. Even though our results showed an over-expression of some potential toxin-related proteins, the cytolytic effect (as assessed by hemolytic, PLA2, and caseinolytic activities) was not increased in bleached M. alcicornis, which suggests that the cytolysis is mainly produced by toxins whose expression was not affected by temperature stress. These findings allow hypothesizing that this hydrocoral is able to prey heterotrophically when suffering from moderate bleaching, giving it a better chance to withstand the effects of high temperature.

Prunus serotina (black cherry), commonly known in Mexico as capulín, is used in Mexican traditional medicine for the treatment of cardiovascular, respiratory, and gastrointestinal diseases. Particularly, P. serotina seeds, consumed in Mexico as snacks, are used for treating cough. In the present study, nutritional and volatile analyses of black cherry seeds were carried out to determine their nutraceutical potential. Proximate analysis indicated that P. serotina raw and toasted seeds contain mostly fat, followed by protein, fiber, carbohydrates, and ash. The potassium content in black cherry raw and toasted seeds is high, and their protein digestibility-corrected amino acid scores suggest that they might represent a complementary source of proteins. Solid phase microextraction and gas chromatography/flame ionization detection/mass spectrometry analysis allowed identification of 59 and 99 volatile compounds in the raw and toasted seeds, respectively. The major volatile compounds identified in raw and toasted seeds were 2,3-butanediol and benzaldehyde, which contribute to the flavor and odor of the toasted seeds. Moreover, it has been previously demonstrated that benzaldehyde possesses a significant vasodilator effect, therefore, the presence of this compound along with oleic, linoleic, and α-eleostearic fatty acids indicate that black cherry seeds consumption might have beneficial effects on the cardiovascular system.

Aim of the study: To evaluate the anti-leishmanial activity and cytotoxicity of aqueous and organic extracts of ten plants used in Mexican traditional medicine as anti-parasitics. Materials and methods: For the organic extracts, plant material was macerated in dichloromethane (CH2Cl2) and dichloromethane/methanol (CH2Cl2/MeOH) (1:1) during two weeks; the aqueous extracts were prepared by infusion. The extracts were tested against promastigotes and intracellular amastigotes of Leishmania amazonensis. The cytotoxicity was assayed in parallel on peritoneal macrophages of BALB/c mice. Results: Four of the thirty extracts tested were active and selective against L. amazonensis promastigotes: Schinus molle (CH2Cl2 and CH2Cl2/MeOH), Lantana camara (CH2Cl2) and Prosopis laevigata (aqueous). These extracts had a median inhibitory concentration (IC50) against intracellular amastigotes under 50 μg/mL and a selectivity index (SI) higher than 5, which indicates that they constitute valuable candidates to obtain secondary metabolites with leishmanicidal activity. Conclusions: The results derived from this study indicate that L. camara, P. laevigata, and S. molle might provide interesting new leads for the development of antileishmanial drugs.

This study focused on the assessment of the vasorelaxant activity of the organic and aqueous extracts obtained from leaves and fruits of a Mexican hawthorn (Crataegus gracilior) on isolated rat aorta, and on the purification and identification of some of their secondary metabolites by the use of chromatographic and spectroscopic techniques. The results obtained showed that the methanol extract has a significantly more potent and effective vasorelaxant effect than the other tested extracts, with an EC50 = 8.69 ± 4.34 µg/mL and an Emax = 94.6% ± 11.30%, values that are close to that of acetylcholine, the positive control. From the same extract, two major triterpenes were isolated and identified as ursolic and corosolic acids by comparison of their experimental NMR spectroscopic data with those reported in the literature. Chlorogenic acid, rutin, quercetin, kaempferol and (+)-catechin were also identified using HPLC coupled with PDAD. All these compounds have already been proven to possess on their own antihypertensive effect and other benefits on cardiovascular diseases and they can support, at least in part, the traditional use of this plant species.

Coral bleaching caused by global warming has resulted in massive damage to coral reefs worldwide. Studies addressing the consequences of elevated temperature have focused on organisms of the class Anthozoa, and up to now, there is little information regarding the mechanisms by which reef forming Hydrozoans face thermal stress. In this study, we carried out a comparative analysis of the soluble proteome and the cytolytic activity of unbleached and bleached Millepora complanata (“fire coral”) that inhabited reef colonies exposed to the 2015−2016 El Niño-Southern Oscillation in the Mexican Caribbean. A differential proteomic response involving proteins implicated in key cellular processes, such as glycolysis, DNA repair, stress response, calcium homeostasis, exocytosis, and cytoskeleton organization was found in bleached hydrocorals. Four of the proteins, whose levels increased in bleached specimens, displayed sequence similarity to a phospholipase A2, an astacin-like metalloprotease, and two pore forming toxins. However, a protein, which displayed sequence similarity to a calcium-independent phospholipase A2, showed lower levels in bleached cnidarians. Accordingly, the hemolytic effect of the soluble proteome of bleached hydrocorals was significantly higher, whereas the phospholipase A2 activity was significantly reduced. Our results suggest that bleached M. complanata is capable of increasing its toxins production in order to balance the lack of nutrients supplied by its symbionts.

Recently, our research group demonstrated that uvaol and ursolic acid increase NO and H2S production in aortic tissue. Molecular docking studies showed that both compounds bind with high affinity to endothelial NO synthase (eNOS) and cystathionine gamma-lyase (CSE). The aim of this study was to identify hits with high binding affinity for the triterpene binding-allosteric sites of eNOS and CSE and to evaluate their vasodilator effect. Additionally, the mechanism of action of the most potent compound was explored. A high-throughput virtual screening (HTVS) of 107,373 compounds, obtained from four ZINC database libraries, was performed employing the crystallographic structures of eNOS and CSE. Among the nine top-scoring ligands, isoxsuprine showed the most potent vasodilator effect. Pharmacological evaluation, employing the rat aorta model, indicated that the vasodilation produced by this compound involved activation of the NO/cGMP and H2S/KATP signaling pathways and blockade of α1-adrenoceptors and L-type voltage-dependent Ca2+ channels. Incubation of aorta homogenates in the presence of isoxsuprine caused 2-fold greater levels of H2S, which supported our preliminary in silico data. This study provides evidence to propose that the vasodilator effect of isoxsuprine involves various mechanisms, which highlights its potential to treat a wide variety of cardiovascular diseases.

In Mexico black cherry (Prunus serotina Ehrh.) fruits are consumed fresh, dried or prepared in jam. Considering the evidence that has linked intake of fruits and vegetables rich in polyphenols to cardiovascular risk reduction, the aim of this study was to characterize the phenolic profile of black cherry fruits and to determine their antioxidant, vasorelaxant and antihypertensive effects. The proximate composition and mineral contents of these fruits were also assessed. Black cherry fruits possess a high content of phenolic compounds and display a significant antioxidant capacity. High-performance liquid chromatography/mass spectrometric analysis indicated that hyperoside, anthocyanins and chlorogenic acid were the main phenolic compounds found in these fruits. The black cherry aqueous extract elicited a concentration-dependent relaxation of aortic rings and induced a significant reduction on systolic blood pressure in L-NAME induced hypertensive rats after four weeks of treatment. Proximate analysis showed that black cherry fruits have high sugar, protein, and potassium contents. The results derived from this study indicate that black cherry fruits contain phenolic compounds which elicit significant antioxidant and antihypertensive effects. These findings suggest that these fruits might be considered as functional foods useful for the prevention and treatment of cardiovascular diseases.

The present paper reviews vasodilator compounds isolated from plants that were reported in the past 22 years (1990 to 2012) and the different mechanisms of action involved in their vasodilator effects. The search for reports was conducted in a comprehensive manner, intending to encompass those metabolites with a vasodilator effect whose mechanism of action involved both vascular endothelium and arterial smooth muscle. The results obtained from our bibliographic search showed that over half of the isolated compounds have a mechanism of action involving the endothelium. Most of these bioactive metabolites cause vasodilation either by activating the nitric oxide/cGMP pathway or by blocking voltage-dependent calcium channels. Moreover, it was found that many compounds induced vasodilation by more than one mechanism. This review confirms that secondary metabolites, which include a significant group of compounds with extensive chemical diversity, are a valuable source of new pharmaceuticals useful for the treatment and prevention of cardiovascular diseases.

Abstract Background: Scleractinian corals (stony corals) are the most abundant reef-forming cnidarians found in coral reefs throughout the world. Despite their abundance and ecological importance, information about the diversity of their toxins and their biological activities is very scarce. In this study, the chemical composition and the biological activities of the aqueous extracts of Pseudodiploria strigosa, Porites astreoides and Siderastrea siderea, three scleractinian corals from the Mexican Caribbean, have been assessed for the first time. Methods: Toxicity of the extracts was assessed in crickets; the presence of cytolysins was detected by the hemolysis assay; the vasoconstrictor activity was determined by the isolated rat aortic ring assay; the nociceptive activity was evaluated by the formalin test. The presence of phospholipases A2 (PLA2), serine proteases, and hyaluronidases was determined by enzymatic methods. Low-molecular-weight fractions were obtained by gel filtration chromatography and ultrafiltration. Results: Extracts from the three species were toxic to crickets, induced hemolysis in human and rat erythrocytes, produced vasoconstriction on isolated rat aortic rings, and presented phospholipase A2 and serine-protease activity. Despite the fact that these corals are not considered to be harmless to humans, the extracts generated significant nociceptive responses. The matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis of the low-molecular-weight fractions revealed the presence of peptides within a mass range of 3000 to 6000 Da. These fractions were toxic to crickets and two of them induced a transitory vasoconstrictor effect on isolated rat aortic rings. Conclusion: This study suggests that scleractinian corals produce low-molecular-weight peptides that are lethal to crickets and induce vasoconstriction.

Arterial hypertension is one of the main risk factors in the development of cardiovascular diseases. Therefore, it is important to look for new drugs to treat hypertension. In this study, we carried out the screening of 19 compounds (triterpenes, diterpenes, sesquiterpenes, lignans, and flavonoids) isolated from 10 plants used in Mexican traditional medicine to determine whether they elicited vascular smooth muscle relaxation and, therefore, could represent novel anti-hypertension drug candidates. The vasorelaxant activity of these compounds was evaluated on the isolated rat aorta assay and the results obtained from this evaluation showed that three compounds induced a significant vasodilatory effect: meso-dihydroguaiaretic acid [half maximal effective concentration (EC50), 49.9 ± 11.2 µM; maximum effect (Emax), 99.8 ± 2.7%]; corosolic acid (EC50, 108.9 ± 6.7 µM; Emax, 96.4 ± 4.2%); and 5,8,4′-trihydroxy-3,7-dimethoxyflavone (EC50, 122.3 ± 7.6 µM; Emax, 99.5 ± 5.4%). Subsequently, involvement of the NO/cyclic guanosine monophosphate (cGMP) and H2S/ATP-sensitive potassium channel (KATP) pathways on the vasodilator activity of these compounds was assessed. The results derived from this analysis showed that the activation of both pathways contributes to the vasorelaxant effect of corosolic acid. On the other hand, the vasodilator effect of meso-dihydroguaiaretic acid and 5,8,4′-trihydroxy-3,7-dimethoxyflavone, partly involves stimulation of the NO/cGMP pathway. However, these compounds also showed an important endothelium-independent vasorelaxant effect, whose mechanism of action remains to be clarified. This study indicates that meso-dihydroguaiaretic acid, corosolic acid, and 5,8,4′-trihydroxy-3,7-dimethoxyflavone could be used as lead compounds for the synthesis of new derivatives with a higher potency to be developed as drugs for the prevention and treatment of cardiovascular diseases.

Analyses of calcium compounds in cladodes, soluble dietary fiber (SDF), and insoluble dietary fiber (IDF) of Opuntia ficus indica are reported. The characterization of calcium compounds was performed by using Scanning Electron Microscopy, Energy Dispersive Spectrometry, X-ray diffraction, and infrared spectroscopy. Atomic Absorption Spectroscopy and titrimetric methods were used for quantification of total calcium and calcium compounds. Whewellite (CaC2O4·H2O), weddellite (CaC2O4·(H2O)2.375), and calcite (CaCO3) were identified in all samples. Significant differences (P≤0.05) in the total calcium contents were detected between samples. CaC2O4·H2O content in cladodes and IDF was significantly higher (P≤0.05) in comparison to that observed in SDF, whereas minimum concentration of CaCO3 was detected in IDF with regard to CaCO3 contents observed in cladodes and SDF. Additionally, molar ratio oxalate : Ca2+ in all samples changed in a range from 0.03 to 0.23. These results support that calcium bioavailability in O. ficus indica modifies according to calcium compounds distribution.

The present research aimed to isolate the non-polar secondary metabolites that produce the vasodilator effects induced by the dichloromethane extract of Prunus serotina (P. serotina) fruits and to determine whether the NO/cGMP and the H2S/KATP channel pathways are involved in their mechanism of action. A bioactivity-directed fractionation of the dichloromethane extract of P. serotina fruits led to the isolation of ursolic acid and uvaol as the main non-polar vasodilator compounds. These compounds showed significant relaxant effect on rat aortic rings in an endothelium- and concentration-dependent manner, which was inhibited by NG-nitro-l-arginine methyl ester (l-NAME), dl-propargylglycine (PAG) and glibenclamide (Gli). Additionally, both triterpenes increased NO and H2S production in aortic tissue. Molecular docking studies showed that ursolic acid and uvaol are able to bind to endothelial NOS and CSE with high affinity for residues that form the oligomeric interface of both enzymes. These results suggest that the vasodilator effect produced by ursolic acid and uvaol contained in P. serotina fruits, involves activation of the NO/cGMP and H2S/KATP channel pathways, possibly through direct activation of NOS and CSE.