1,721,068 research outputs found
Neutral/negative α 1 -AR antagonists and calcium channel blockers at comparison in functional tests on guinea-pig smooth muscle and myocardium
No full textBackground: Constitutive (agonist-independent) activity is a prerogative of many G protein-coupled receptors (GPCRs) including α 1 -adrenoceptors (α 1 -ARs). Inhibition of such an activity at α 1 -AR subtypes by antagonists with negative efficacy is difficult to be adequately tested. Methods: In the present experimental approach, we compared the activity of three calcium channel blockers (nifedipine, diltiazem and verapamil) and of three potent benzodioxane-based α 1 -AR antagonists, differing for subtype selectivity and inverse agonist properties, in producing smooth muscle relaxation and negative inotropy under the same test conditions. We selected, as benzodioxane derivatives, (S)-WB4101, inverse agonist with slight α 1A /α 1B -α 1D AR selectivity, and two previously developed analogues. Both of these are potent antagonists at α 1D -AR, that is the α 1 - AR subtype suspected of the highest susceptibility to inverse agonists for its high degree of basal activity, but only one is inverse agonist. Results: We found that all the three benzodioxane-related α 1 -AR antagonists have significant intrinsic relaxant activity on non-vascular smooth muscle and moderate negative inotropic effect, while they do not relax aorta. Their potency is always lower than that of three calcium channel blockers. Conclusions: Intrinsic myorelaxant and negative inotropic activity of the three benzodioxane-based α 1 -AR antagonist is related neither to a particular profile of α 1 -AR subtype selectivity nor to whether or not being an inverse agonist, but it parallels the calcium antagonists effects indicating a direct interaction of the three α 1 -AR antagonists with L-type Ca 2+ channels
The effects of experimental conditions on extraction of polyphenols from African Nutmeg peels using NADESs-UAE: a multifactorial modelling technique
No full textAbstract Extraction of polyphenolic compounds from African nutmeg (Monodora myristica (Gaertn.)) peels using natural acidic deep eutectic solvents coupled to ultrasound-assisted extraction (NADESs-UAE) followed many factors at a time (MFAT) screening with response surface optimization was investigated. Fourteen different NADESs based on citric acid as hydrogen bond acceptor (HBA) were designed and tested. Sucrose, fructose, xylitol, glycerol, glycine, and glucose were used as hydrogen bond donors (HBDs). The responses studied are total phenolic compounds (TPC), total flavonoid compounds (TFC), and antioxidant activity (AA) based on cupric ion reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP). The UAE procedure was optimized with the most efficient NADES. Quadratic models produced satisfactory fitting of the experimental data regarding TPC (R2 = 0.9999, p < 0.0001), TFC (R2 = 0.9991, p < 0.0001), and AA- CUPRAC (R2 = 0.9988, p < 0.0001) and FRAP (R2 = 1.000, P < 0001). Ultrasound temperature 30°c, extraction time 5 min, solvent volume 25 ml, and solvent concentration 90% (v/v) were considered optimal conditions for the extraction models resulting in TPC 1290.9 ± 5.6 mg/g GAE db, TFC 2398.7 ± 23 µg/g QE db, CUPRAC 38.46 ± 0.4.4 µmol/g TE db, and FRAP 26.15 ± 0.11µmol/g TE db, respectively
Hibiscus Sabdariffa L. Flowers and Olea Europea L. Leaves Extract-Based Formulation for Hypertension Care: In Vitro Efficacy and Toxicological Profile
No full textOlea europaea L. leaves extract (Oe) and Hybiscus sabdariffa L. flowers extract (Hs) have calcium antagonistic properties. Aim of this work was to study the cardiovascular effects of Pres Phytum(®), a nutraceutical formulation containing a mixture of the two extracts and the excipients, and investigate its possible off-target effects, using in vitro biological assays on guinea pig isolated organs. Cardiovascular effects were assessed using guinea pig atria and aorta. The effects of Pres Phytum on spontaneous gastrointestinal, urinary, and respiratory tracts smooth muscle contractility were evaluated. Pres Phytum exerted a vasorelaxant effect (IC50 = 2.38 mg/mL) and a negative chronotropic effect (IC50 = 1.04 mg/mL) at concentrations lower than those producing smooth muscle spontaneous contractility alterations in the other organs. Compared to Pres Phytum, the mixture did not exert negative inotropic activity, while it maintained a negative chronotropic efficacy (IC50 = 1.04 mg/mL). These experimental data suggest a possible nutraceutical use of this food supplement for the management of preclinical hypertension
Apoptotic-induced Effects of Castanea sativa Bark Extract in Human SH-SY5Y Neuroblastoma Cells
No full textCastanea sativa Mill. wood extract (ENC) has health-promoting qualities such as antibacterial, antiviral, antispasmodic, cardio- and neuroprotective-activities. Its potential towards cancer cells of the central nervous system, however, is still unexplored. This study investigates the apoptotic-enhancing effect of ENC in human neuroblastoma SH-SY5Y cell line. This extract irreversibly decreased cell viability with IC50 of 142.8±20.2, 109.3±16.6 and 82.5±8.6 μg/mL for 24h, 48 and 72h of treatment, respectively. This was accompanied by cell shrinkage and tendency to round-up. A concentration-dependent increase in sub G0/G1 cells as well as a rise in cells with nuclear fragmentation and chromatin condensation, both typical of apoptosis, was also observed. In conclusion, the present findings provide initial data on the potential of ENC for neuroblastoma treatment and offer the rationale for further studies aimed at elucidating the full mechanism(s) underlying its effects
Long COVID‐19 gastrointestinal related disorders and traditional Chinese medicine: A network target‐based approach
No full text: The significant number of individuals impacted by the pandemic makes prolonged symptoms after COVID-19 a matter of considerable concern. These are numerous and affect multiple organ systems. According to the World Health Organization (WHO), prolonged gastrointestinal issues are a crucial part of post-COVID-19 syndrome. The resulting disruption of homeostasis underscores the need for a therapeutic approach based on compounds that can simultaneously affect more than one target/node. The present review aimed to check for nutraceuticals possessing multiple molecular mechanisms helpful in relieving Long COVID-19-specific gastrointestinal symptoms. Specific plants used in Keywords Chinese Medicine (TCM) expected to be included in the WHO Global Medical Compendium were selected based on the following criteria: (1) they are widely used in the Western world as natural remedies and complementary medicine adjuvants; (2) their import and trade are regulated by specific laws that ensure quality and safety (3) have the potential to be beneficial in alleviating intestinal issues associated with Long COVID-19. Searches were performed in PubMed, Elsevier, Google Scholar, Scopus, Science Direct, and ResearchGate up to 2023. Cinnamomum cassia, Glycyrrhiza uralensis, Magnolia officinalis, Poria cocos, Salvia miltiorrhiza, Scutellaria baicalensis, and Zingiber officinalis were identified as the most promising for their potential impact on inflammation and oxidative stress. Based on the molecular mechanisms of the phytocomplexes and isolated compounds of the considered plants, their clinical use may lead to benefits in gastrointestinal diseases associated with Long COVID-19, thanks to a multiorgan and multitarget approach
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