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Sestrins (SESNs) are a family of evolutionarily conserved proteins among mammals. They have several body homeostatic functions such as antioxidant, metabolic, and anti-aging, and are required to regenerate hyperoxidized forms of peroxiredoxins and reactive oxygen species. Sestrin 2 has been studied as a therapeutic agent in obesity treatment. Gallic acid (GA) is a triphenolic compound with beneficial biological activities including anti-inflammatory, antidiabetic, antihypertensive, and antioxidant effects. Recent studies demonstrated the GA's ability to reduce body weight gain and improve glycemic parameters. In this sense, the present study aims to investigate the GA activating potential of Sestrin using the molecular docking method. The 3D structure of gallic acid was retrieved from the NCBI PubChem database and the chemical structure of the Sestrin2 protein from the RCSB Protein Data Bank (5DJ4). The docking calculus was performed via UCSF Chimera and AutoDock Vinaprograms. The results showed that amino acids Arg390, Glu451, Trp444, Thr386, Arg448, Thr374, Tyr375, Asn376, Thr377, Leu389, His454, Ser450, His86, and Val455 are very important for GA stabilization, resembling the interactions that permit Leucine to activate SESN2. In this context, the obesity therapeutic property of GA can be understood from a Sestrin activating process through amino acid metabolism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Hibiscus sabdariffa L. is a worldwide component for tea and beverages, being a natural source of anthocyanins, which are associated with cardiovascular activities. To investigate this relationship, we explored different methods of aqueous extraction on the anthocyanin content and antioxidant activity of H. sabdariffa L. calyx extract (HSCE). Pharmacological effects via platelet aggregation, calcium mobilization, cyclic nucleotide levels, vasodilator-stimulated phosphoprotein Ser157 and Ser239, and on the vasomotor response of aortic rings isolated from mice are studied herewith. We found that the application of ultrasonic turbolization, 20 min, combined with acidified water was significantly more effective in the extraction process, providing extracts with the highest levels of anthocyanins (8.73 and 9.63 mg/100 g) and higher antioxidant activity (6.66 and 6.78 μM trolox/g of sample). HSCE significantly inhibited (100-1000 μg/mL) arachidonic acid-induced platelet aggregation, reduced calcium mobilization, and increased cAMP and cGMP levels with VASPSer157 and VASPSer239 phosphorylation. Vasorelaxation reduction was confirmed by the aortic rings and endothelium assays treated with nitric oxide synthase inhibitors, soluble guanylyl cyclase (sGC) oxidizing agent, or Ca 2+ -activated K + channel inhibitor. The increasing of cGMP levels could be understood considering the sGC stimulation by HSCE compounds in the specific stimulus domain, which allows an understanding of the observed antiplatelet and vasorelaxant properties of H. sabdariffa L. calyx extract., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alibertia edulis leaf extract is commonly used in folk medicine, with rutin caffeic and vanillic acids being its major compounds. The Alibertia edulis leaf extract was investigated for its pharmacological effects via platelet aggregation, calcium mobilization, cyclic nucleotides levels, vasodilator-stimulated phosphoprotein Ser157 and Ser239 and protein kinase Cβ 2 phosphorylation, thromboxane B 2 , cyclooxygenases 1 and 2, docking and molecular dynamics. Alibertia edulis leaf extract significantly inhibited (100-1000 μg mL -1 ) platelet aggregation induced by different agonists. Arachidonic acid increased levels of calcium and thromboxane B 2 , phosphorylation of vasodilator-stimulated phosphoprotein Ser157 and Ser239, and protein kinase Cβ, which were significantly reduced by Alibertia edulis leaf extract, rutin, and caffeic acid as well mixtures of rutin/caffeic acid. Cyclooxygenase 1 activity was inhibited for Alibertia edulis leaf extract, rutin and caffeic acid. These inhibitions were firsrtly explored by specific stabilization of rutin and caffeic acid compared to diclofenac at the catalytic site from docking score and free-energy dissociation profiles. Then, simulations detailed the rutin interactions close to the heme group and Tyr385, responsible for catalyzing the conversion of arachidonic acid to its products. Our results reveal the antiplatelet aggregation properties of Alibertia edulis leaf extract, rutin and caffeic acid providing pharmacological information about its origin from cyclooxygenase 1 inhibition and its downstream pathway.

Phosphodiesterase type 5 (PDE-5) is an important enzyme involved in the hydrolysis of cyclic guanosine monophosphate (cGMP) to guanosine monophosphate (GMP). The inhibition of this protein leads to the accumulation of cGMP in cells with various biological and therapeutic effects. Several PDE-5 inhibitors exist, with Tadalafil being one of the most commonly studied and used in clinical therapy. In this study, we applied Molecular Dynamics simulations coupled to the ABF (Adaptive Biasing Force) method to study the effect of the mutation on the Gln817 residue (Q817G). The results of the free energy profiles made clear that the affinity of the inhibitor for PDE-5 is dependent on the amino acid residue Gln817. The hydrogen bond made between the side chain of glutamine and the indole ring of Tadalafil results in the stabilization of the ligand in the catalytic site. Despite the prominent role of this interaction, it is important to highlight the contribution of other residues of the catalytic domain for the stabilization of the compound, due to the set of polar, hydrophobic and electrostatic interactions performed by specific amino acid residues., (© 2018 John Wiley & Sons A/S.)

Campomanesia adamantium is a medicinal plant of the Brazilian Cerrado. Different parts of its fruits are used in popular medicine to treat gastrointestinal disorders, rheumatism, urinary tract infections and inflammations. Despite its widespread use by the local population, the mechanisms involving platelet aggregation and the inhibition of cyclooxygenase by C. adamantium are unknown. This study evaluated the chemical composition, antioxidant activities and potential benefits of the C. adamantium peel extract (CAPE) and its components in the platelet aggregation induced by arachidonic acid in platelet-rich plasma. Aspects of the pharmacological mechanism were investigated as follows: platelet viability, calcium mobilization, levels of the cyclic nucleotides cAMP and cGMP, thromboxane B 2 levels, and the inhibitory effects on COX-1 and COX-2 were studied in vitro and using molecular docking in the catalytic domain of these proteins. The major CAPE constituents standing out from the chemical analysis are the flavonoids, namely those of the flavones and chalcones class. The results showed that CAPE, quercetin and myricetin significantly decreased arachidonic acid-induced platelet aggregation; the assays showed that CAPE and quercetin decreased the mobilization of calcium and thromboxane B 2 levels in platelets and increased cAMP and cGMP levels. Moreover, CAPE inhibited the activity of COX-1 and COX-2, highlighting that quercetin could potentially prevent the access of arachidonic acid more to the catalytic site of COX-1 than COX-2. These results highlight CAPE's potential as a promising therapeutic candidate for the prevention and treatment of diseases associated with platelet aggregation.

The techniques used to monitor the quality of the biodiesel are intensely discussed in the literature, partly because of the different oil sources and their intrinsic physicochemical characteristics. This study aimed to monitor the thermal degradation of the fatty acid methyl esters of Sesamum indicum L. and Raphanus sativus L. biodiesels (SILB and RSLB, resp.). The results showed that both biodiesels present a high content of unsaturated fatty acids, ∼84% (SILB) and ∼90% (RSLB). The SILB had a high content of polyunsaturated linoleic fatty acid (18  :  2), about 49%, and the oleic monounsaturated (18  :  1), ∼34%. On the other hand, RSLB presented a considerable content of linolenic fatty acid (18  :  3), ∼11%. The biodiesel samples were thermal degraded at 110°C for 48 hours, and acid value, UV absorption, and fluorescence spectroscopy analysis were carried out. The results revealed that both absorption and fluorescence presented a correlation with acid value as a function of degradation time by monitoring absorptions at 232 and 270 nm as well as the emission at 424 nm. Although the obtained correlation is not completely linear, a direct correlation was observed in both cases, revealing that both properties can be potentially used for monitoring the biodiesel degradation.