-
PloS One 2023Ephedra sinica Stapf. is a shrubby plant widely used in traditional Chinese medicine due to its high level of medicinal value, thus, it is in high demand. Ephedrine (E)...
Ephedra sinica Stapf. is a shrubby plant widely used in traditional Chinese medicine due to its high level of medicinal value, thus, it is in high demand. Ephedrine (E) and pseudoephedrine (PE) are key medicinal components and quality indicators for E. sinica. These two ephedrine-type alkaloids are basic elements that exert the medicinal effect of E. sinica. Recently, indiscriminate destruction and grassland desertification have caused the quantity and quality of these pharmacological plants to degenerate. Predicting potentially suitable habitat for high-quality E. sinica is essential for its future conservation and domestication. In this study, MaxEnt software was utilized to map suitable habitats for E. sinica in Inner Mongolia based on occurrence data and a set of variables related to climate, soil, topography and human impact. The model parametrization was optimized by evaluating alternative combinations of feature classes and values of the regularization multiplier. Second, a geospatial quality model was fitted to relate E and PE contents to the same environmental variables and to predict their spatial patterns across the study area. Outputs from the two models were finally coupled to map areas predicted to have both suitable conditions for E. sinica and high alkaloid content. Our results indicate that E. sinica with high-quality E content was mainly distributed in the Horqin, Ulan Butong and Wulanchabu grasslands. E. sinica with high-quality PE content was primarily found in the Ordos, Wulanchabu and Ulan Butong grasslands. This study provides scientific information for the protection and sustainable utilization of E. sinica. It can also help to control and prevent desertification in Inner Mongolia.
Topics: Humans; Ephedrine; Ephedra sinica; Alkaloids; Drugs, Chinese Herbal; China; Pseudoephedrine; Ephedra
PubMed: 37083689
DOI: 10.1371/journal.pone.0283967 -
Blood Pressure Dec 2022Beta-blockers have solid documentation in preventing cardiovascular complications in the treatment of hypertension; atenolol, metoprolol, oxprenolol and propranolol... (Review)
Review
Diverse pharmacological properties, trial results, comorbidity prescribing and neural pathophysiology suggest European hypertension guideline downgrading of beta-blockers is not justified.
Beta-blockers have solid documentation in preventing cardiovascular complications in the treatment of hypertension; atenolol, metoprolol, oxprenolol and propranolol demonstrate proven cardiovascular prevention in hypertension mega-trials. Hypertension is characterised by activation of the sympathetic nervous system from early to late phases, which makes beta-blockers an appropriate treatment seen from a pathophysiological viewpoint, especially in patients with an elevated heart rate. Beta-blockers represent a heterogenous class of drugs with regard to both pharmacodynamic and pharmacokinetic properties. This position is manifest by reference to another clinical context, beta-blocker treatment of heart failure, where unequivocally there is no class effect (no similar benefit from all beta-blockers); there are good and less good beta-blockers for heart failure. Analogous differences in beta-blocker efficacy is also likely in hypertension. Beta-blockers are widely used for the treatment of diseases comorbid with hypertension, in approximately 50 different concomitant medical conditions that are frequent in patients with hypertension, leading to many de facto beta-blocker first choices in clinical practice. Thus, beta-blockers should be regarded as relevant first choices for hypertension in clinical practice, particularly if characterised by a long half-life, highly selective beta-1 blocking activity and no intrinsic agonist properties.SUMMARYBeta-blockers have solid documentation in preventing cardiovascular complications in the treatment of hypertension; atenolol, metoprolol, oxprenolol and propranolol demonstrate proven cardiovascular prevention in hypertension mega-trialsHypertension is characterised by activation of the sympathetic nervous system from early to late phases, which makes beta-blockers an appropriate treatment seen from a pathophysiological viewpoint, especially in patients with an elevated heart rateBeta-blockers represent a heterogenous class of drugs with regard to both pharmacodynamic and pharmacokinetic propertiesThis position is manifest by reference to another clinical context, beta-blocker treatment of heart failure, where unequivocally there is no class effect (no similar benefit from all beta-blockers); there are good and less good beta-blockers for heart failureAnalogous differences in beta-blocker efficacy is also likely in hypertensionBeta-blockers are widely used for the treatment of diseases comorbid with hypertension, in approximately 50 different concomitant medical conditions that are frequent in patients with hypertension, leading to many de facto beta-blockers first choices in clinical practiceThese observations, in totality, inform our opinion that beta-blockers are relevant first choices for hypertension in clinical practice and this fact needs highlightingFurther, these arguments suggest European hypertension guideline downgrading of beta-blockers is not justified.
Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Atenolol; Cardiovascular Diseases; Comorbidity; Heart Failure; Humans; Hypertension; Metoprolol; Oxprenolol; Propranolol
PubMed: 36029011
DOI: 10.1080/08037051.2022.2110858 -
Molecules (Basel, Switzerland) Oct 2020Extracts of [L.] Kunth have previously been demonstrated to have in vivo estrogenic-like effects, thereby functioning as an anti-osteoporotic agent. However, the...
Extracts of [L.] Kunth have previously been demonstrated to have in vivo estrogenic-like effects, thereby functioning as an anti-osteoporotic agent. However, the compounds responsible for these effects have not yet been determined. Therefore, the aim of this study is to isolate and elucidate potential compounds with estrogenic activity. The structures of the isolated compounds were identified using 1D H and C-NMR and confirmed by 2D FT-NMR. The estrogenic activity was evaluated using the E-SCREEN assay, and a molecular docking study was performed to predict the binding affinity of the isolated compounds to estrogen receptors. In this experiment, we successfully isolated three phenylpropanoids and two lignan derivatives, namely, 6-allyl-5-methoxy-1,3-benzodioxol-4-ol (), pachypostaudin B (), pellucidin A (), dillapiole (), and apiol (). Among these compounds, the isolation of and from is reported for the first time in this study. Activity assays clearly showed that the ethyl acetate extract and its fractions, subfractions, and isolated compounds exerted estrogenic activity. Methanol fraction of the ethyl acetate extract produced the highest estrogenic activity, while and had partial agonist activity. Some compounds (derivates of dillapiole and pellucidin A) also had, in addition, anti-estrogenic activity. In the docking study, the estrogenic activities of - appeared to be mediated by a classical ligand-dependent mechanism as suggested by the binding interaction between the compounds and estrogen receptors; binding occurred on Arg 394 and His 524 of the alpha receptor and Arg 346 and His 475 of the beta receptor. In summary, we reveal that is a promising anti-osteoporotic agent due to its estrogenic activity, and the compounds responsible for this activity were found to be lignan and phenylpropanoid derivatives. The presence of other compounds in either the extract or fraction may contribute to a synergistic effect, as suggested by the higher estrogenic activity of the methanol fraction. Hence, we suggest further research on the osteoporotic activity and safety of the identified compounds, especially regarding their effects on estrogen-responsive organs.
Topics: Estrogen Receptor alpha; Estrogen Receptor beta; Humans; Lignans; MCF-7 Cells; Models, Molecular; Molecular Docking Simulation; Peperomia; Phytoestrogens; Propanols
PubMed: 33114252
DOI: 10.3390/molecules25214914 -
Journal of Molecular Biology Jun 2023Membranes form the first line of defence of bacteria against potentially harmful molecules in the surrounding environment. Understanding the protective properties of...
Membranes form the first line of defence of bacteria against potentially harmful molecules in the surrounding environment. Understanding the protective properties of these membranes represents an important step towards development of targeted anti-bacterial agents such as sanitizers. Use of propanol, isopropanol and chlorhexidine can significantly decrease the threat imposed by bacteria in the face of growing anti-bacterial resistance via mechanisms that include membrane disruption. Here we have employed molecular dynamics simulations and nuclear magnetic resonance to explore the impact of chlorhexidine and alcohol on the S. aureus cell membrane, as well as the E. coli inner and outer membranes. We identify how sanitizer components partition into these bacterial membranes, and show that chlorhexidine is instrumental in this process.
Topics: Anti-Bacterial Agents; Chlorhexidine; Escherichia coli; Magnetic Resonance Spectroscopy; Staphylococcus aureus; Cell Membrane; 1-Propanol; 2-Propanol; Hand Sanitizers
PubMed: 37330283
DOI: 10.1016/j.jmb.2023.167953 -
European Journal of Pharmaceutical... Feb 2023Most drugs, especially those with acidic or neutral moieties, are bound to the plasma protein albumin, whereas basic drugs are preferentially bound to human alpha-1-acid...
Most drugs, especially those with acidic or neutral moieties, are bound to the plasma protein albumin, whereas basic drugs are preferentially bound to human alpha-1-acid glycoprotein (AGP). The protein binding of the long-established drugs ephedrine and pseudoephedrine, which are used in the treatment of hypotension and colds, has so far only been studied with albumin. Since in a previous study a stereoselective binding of ephedrine and pseudoephedrine to serum but not to albumin was observed, the aim of this study was to check whether the enantioselective binding behavior of ephedrine and pseudoephedrine, in addition to the derivatives methylephedrine and norephedrine, is due to AGP and to investigate the influence of their different substituents and steric arrangement. Discontinuous ultrafiltration was used for the determination of protein binding. Characterization of ligand-protein interactions of the drugs was obtained by saturation transfer difference nuclear magnetic resonance spectroscopy. Docking experiments were performed to analyze possible ligand-protein interactions. The more basic the ephedrine derivative is, the higher is the affinity to AGP. There was no significant difference in the binding properties between the individual enantiomers and the diastereomers of ephedrine and pseudoephedrine.
Topics: Humans; Ephedrine; Ligands; Orosomucoid; Phenylpropanolamine; Protein Binding; Pseudoephedrine
PubMed: 36402307
DOI: 10.1016/j.ejps.2022.106333 -
Angewandte Chemie (International Ed. in... Jun 2022Caryoynencin is a toxic and antifungal fatty acid derivative produced by a number of plant-pathogenic and insect-protective bacteria (Trinickia caryophylli and...
Caryoynencin is a toxic and antifungal fatty acid derivative produced by a number of plant-pathogenic and insect-protective bacteria (Trinickia caryophylli and Burkholderia spp.). In addition to the reactive tetrayne unit, the presence of an allylic alcohol moiety is critical for antimicrobial activities. By a combination of mutational analyses, heterologous expression and in vitro reconstitution experiments we show that the cytochrome P450 monooxygenase CayG catalyzes the complex transformation of a saturated carbon backbone into an allylic alcohol. Unexpectedly, CayG employs a ferritin-like protein (CayK) or a rubredoxin (CayL) component for electron transport. A desaturation-hydroxylation sequence was deduced from a time-course study and in vitro biotransformations with pathway intermediates, substrate analogues, protegencin congeners from Pseudomonas protegens Pf-5, and synthetic derivatives. This unusual multifunctional oxygenase may inspire future biocatalytic applications.
Topics: Cytochrome P-450 Enzyme System; Hydroxylation; Oxidation-Reduction; Propanols
PubMed: 35416382
DOI: 10.1002/anie.202203264 -
Scientific Reports Jan 2021Beta-adrenergic blocking agents (abbreviated as beta-blockers) have been used for treating various cardiovascular diseases. However, the potential for asthma... (Meta-Analysis)
Meta-Analysis
Beta-adrenergic blocking agents (abbreviated as beta-blockers) have been used for treating various cardiovascular diseases. However, the potential for asthma exacerbation is one of the major adverse effects of beta-blockers. This study aimed to compare the level of risk for an asthma attack in patients receiving various beta-blockers. We searched for randomized controlled trials (RCTs) of either placebo-controlled or active-controlled design. The current network meta-analysis (NMA) was conducted under a frequentist model. The primary outcome was the incidence of asthmatic attack. A total of 24 RCTs were included. Overall NMA revealed that only oral timolol [risk ratio (RR) = 3.35 (95% confidence interval (CI) 1.04-10.85)] and infusion of propranolol [RR = 10.19 (95% CI 1.29-80.41)] were associated with significantly higher incidences of asthma attack than the placebo, whereas oral celiprolol [RR = 0.39 (95% CI 0.04-4.11)], oral celiprolol and propranolol [RR = 0.46 (95% CI 0.02-11.65)], oral bisoprolol [RR = 0.46 (95% CI 0.02-11.65)], oral atenolol [RR = 0.51 (95% CI 0.20-1.28)], infusion of practolol [RR = 0.80 (95% CI 0.03-25.14)], and infusion of sotalol [RR = 0.91 (95% CI 0.08-10.65)] were associated with relatively lower incidences of asthma attack than the placebo. In participants with a baseline asthma history, in addition to oral timolol and infusion of propranolol, oral labetalol, oxprenolol, propranolol, and metoprolol exhibited significantly higher incidences of asthma attack than did the placebo. In conclusion, oral timolol and infusion of propranolol were associated with a significantly higher risk of developing an asthma attack in patients, especially in those with a baseline asthma history, and should be avoided in patients who present a risk of asthma.Trial registration: PROSPERO CRD42020190540.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Atenolol; Bisoprolol; Cardiovascular Diseases; Celiprolol; Disease Progression; Female; Humans; Incidence; Infusions, Intravenous; Male; Practolol; Propranolol; Randomized Controlled Trials as Topic; Risk; Sotalol; Status Asthmaticus; Timolol
PubMed: 33432057
DOI: 10.1038/s41598-020-79837-3 -
BMC Oral Health Dec 2022Disinfection of surgical guides is mandatory for intraoperative use. Virgin Coconut Oil may be a potent alternative disinfectant; however, its effect has not been fully...
BACKGROUND/OBJECTIVES
Disinfection of surgical guides is mandatory for intraoperative use. Virgin Coconut Oil may be a potent alternative disinfectant; however, its effect has not been fully discussed in dentistry. The objectives of this study were to compare the morphological and the volumetric dimensional changes of 3D printed surgical guides after immersion in three disinfectants: 100%Virgin Coconut Oil, 2% Glutaraldehyde, and 70% Ethyl Alcohol and to assess the antimicrobial effectiveness of the tested disinfectants.
MATERIALS AND METHODS
A surgical guide was designed using open platform software to print thirty guides and then cut them into two halves (N = 60). Pre-disinfection scans of the first half of the three study groups (n = 30) were performed using Cone-beam Computed Tomography, then immersed for 20 min in three disinfectants as follows: group VCO was immersed in 100% Virgin Coconut Oil, group GA was immersed in 2% Glutaraldehyde, and group EA was immersed in 70% Ethyl Alcohol. Post-disinfection scans of the first half of the three study groups (n = 30) were performed and then compared morphologically and volumetrically using an analyzing software program The second half of the three control groups (n* = 30) were soaked for 20 min in sterile distilled water as follows: group VCO*, group GA*, and group EA* for the assessment of the antimicrobial effectiveness of the three tested disinfectants.
RESULTS
At the morphological assessment of the dimensional changes, group VCO were the most accurate with the lowest mean deviation value of 0.12 ± 0.02 mm and root mean square value of 0.12 mm, group GA and group EA were less accurate with mean deviation value of = 0.22 ± 0.05 mm and = 0.19 ± 0.03 mm and root mean square value of 0.22 and 0.20 respectively (p < 0.001). At the volumetric assessment, group VCO showed lower volumetric changes with a mean deviation value of 0.17 ± 0.10 mm, root mean square value of 0.19 mm, than group GA with mean deviation value of 0.23 ± 0.10 mm, root mean square value of 0.25 mm and group EA with mean deviation value of 0.27 ± 0.11 mm, root mean square value of 0.29 mm, however, no statistically significant differences were found between the three study groups (p = 0.10). The antimicrobial effectiveness of the three tested disinfectants showed a hundred percent (100%) reduction in the total microbial count in the first half of the three study groups treated with the three disinfectants revealing no bacterial growth, however, statistically significant differences were found between the second half of the three control and the first half of the three study groups. (p < 0.001).
CONCLUSIONS
Virgin Coconut Oil showed higher morphological dimensional accuracy of the tested surgical guides than Glutaraldehyde and Ethyl Alcohol without causing any volumetric dimensional changes in the 3D printed surgical guides after disinfection for 20 min and the antimicrobial effectiveness was the same between the three tested disinfectants without showing any microbial growth.
Topics: Humans; Glutaral; Coconut Oil; Anti-Infective Agents; Disinfectants; 2-Propanol; Ethanol; Printing, Three-Dimensional
PubMed: 36564796
DOI: 10.1186/s12903-022-02671-8 -
Plant, Cell & Environment May 2021With diverse genetic backgrounds, soybean landraces are valuable resource for breeding programs. Herein, we apply multi-omic approaches to extensively characterize the...
With diverse genetic backgrounds, soybean landraces are valuable resource for breeding programs. Herein, we apply multi-omic approaches to extensively characterize the molecular basis of drought tolerance in the soybean landrace LX. Initial screens established that LX performed better with PEG6000 treatment than control cultivars. LX germinated better than William 82 under drought conditions and accumulated more anthocyanin and flavonoids. Untargeted mass spectrometry in combination with transcriptomic analyses revealed the chemical diversity and genetic basis underlying the overall performance of LX landrace. Under control and drought conditions, significant differences in the expression of a suite of secondary metabolism genes, particularly those involved in the general phenylpropanoid pathway and flavonoid but not lignin biosynthesis, were seen in LX and William 82. The expression of these genes correlated with the corresponding metabolites in LX plants. Further correlation analysis between metabolites and transcripts identified pathway structural genes and transcription factors likely are responsible for the LX agronomic traits. The activities of some key biosynthetic genes or regulators were confirmed through heterologous expression in transgenic Arabidopsis and hairy root transformation in soybean. We propose a regulatory mechanism based on flavonoid secondary metabolism and adaptive traits of this landrace which could be of relevance to cultivated soybean.
Topics: Anthocyanins; Droughts; Flavonoids; Gene Expression Profiling; Gene Expression Regulation, Plant; Genomics; Germination; Metabolome; Metabolomics; Phenotype; Propanols; Quantitative Trait, Heritable; Reproducibility of Results; Secondary Metabolism; Glycine max; Stress, Physiological; Transcription Factors; Transcriptome
PubMed: 33554357
DOI: 10.1111/pce.14025 -
Organic Letters Jul 2020Hexafluoroisopropanol (HFIP)-promoted disulfidation and diselenation of C-C unsaturated bonds is reported. Reactions of unactivated alkyne, alkene, and allene,...
Hexafluoroisopropanol (HFIP)-promoted disulfidation and diselenation of C-C unsaturated bonds is reported. Reactions of unactivated alkyne, alkene, and allene, respectively, with disulfides or diselenides in HFIP led to desired products in good to excellent yields (up to 96%). In contrast, other solvents, such as isopropanol and dichloroethane, could not promote the same reaction. This method revealed an example of HFIP-promoted transformations under the mild conditions, which greatly highlighted the unique reactivity of this special solvent.
Topics: Alkenes; Alkynes; Catalysis; Organoselenium Compounds; Propanols; Solvents; Sulfides
PubMed: 32588633
DOI: 10.1021/acs.orglett.0c01834