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Frontiers in Pharmacology 2021The genus Thymus is traditionally used for the treatment of hyperactive airways complaints. The purpose of the current study is to investigate the potential tracheal...
The genus Thymus is traditionally used for the treatment of hyperactive airways complaints. The purpose of the current study is to investigate the potential tracheal relaxant effect and possible mechanism(s) of the essential oil of (TS Oil) in isolated guinea pig tracheal tissues. The essential oil was obtained from the fresh erial parts of , and its phyto-components were identified by GC-MS analysis. Guinea pig tracheal preparations were used for testing the tracheal relaxant effect of TS Oil with the determination of the mechanism(s) involved in this relaxation. GC-MS findings reveal that terpenes, fragrance constituents, saponins, and higher fatty acids are present in TS Oil. In isolated guinea pig trachea, TS Oil inhibited carbachol (CCh, 1 µM) and K (80 mM)-induced contractions in a pattern similar to that of dicyclomine. TS Oil, at 0.3 mg/ml, shifted parallel CCh-curves towards the right, followed by a non-parallel shift at higher concentration (1 mg/ml), thus suppressing maximum response in the same manner as produced by dicyclomine. Pretreatment of tissues with TS Oil (1 and 3 mg/ml) also produced a rightward shift of Ca concentration-response curves (CRCs) in the same manner as caused by verapamil. Further, TS Oil at low concentrations (0.3 and 1 mg/ml) shifted isoprenaline-induced inhibitory CRCs towards the left and increased cAMP levels in isolated tracheal homogenates similar to papaverine, a phosphodiesterase (PDE) inhibitor. In the antimicrobial assay performed by the agar well diffusion method, TS Oil was found most active against and where the zone of inhibition measured was 28 mm. Additionally, there was little difference between standard strains of gram-positive and gram-negative bacteria. However, methicillin-resistant (MRSA) showed a small zone of inhibition as compared to standard strains (22 mm). From these results, it can be concluded that the essential oil of has the potential to produce antimicrobial effects while causing tracheal relaxation mediated possibly by anticholinergic effects, Ca channel blockade, and PDE inhibition whereas additional mechanism(s) cannot be ruled out.
PubMed: 33883992
DOI: 10.3389/fphar.2021.615228 -
Evidence-based Complementary and... 2020Aqueous-methanolic crude extracts of Flaxseed (Fs.Cr) and Flaxseed oil were tested against 6% acetic acid- (AA-) induced colitis in BALB/c mice. Microscopic damage...
MATERIALS AND METHODS
Aqueous-methanolic crude extracts of Flaxseed (Fs.Cr) and Flaxseed oil were tested against 6% acetic acid- (AA-) induced colitis in BALB/c mice. Microscopic damage parameters of the hematoxylin and eosin-stained and periodic acid-Schiff-alcian blue-stained sections of the colon were scored to be assessed. Possible antispasmodic mechanism was studied on isolated rabbit jejunum, while antibacterial activity was assessed for microbes implicated in IBD.
RESULTS
In AA-induced colitis, Flaxseed oil was found to be more effective in reducing mortality and colonic ulcers than Fs.Cr at 500 mg/kg dose. Fs.Cr was more efficacious in increasing mucin content as compared to oil, exhibiting slightly greater anti-inflammatory effect (50% vs 35%) and reducing depth of lesion (55% vs 42.31%, respectively). Antispasmodic activity of Fs.Cr (0.03 and 0.1 mg/ml) was mediated by phosphodiesterase inhibitors (PDEI, possibly PDE-4 subtype) with a resultant increase in cAMP levels. Flaxseed oil PDEI activity was mild (1 and 3 mg/ml). Fs.Cr (0.1 and 0.3 mg/ml) was potent in exhibiting anticholinergic activity, similar to dicyclomine, whereas Flaxseed oil showed anticholinergic effect at 1 and 3 mg/ml. Flaxseed oil (9 and 14 g/ml) was bactericidal against enteropathogenic (EPEC), enterotoxigenic (ETEC), and enteroaggregative (EAEC), whereas Fs.Cr exhibited bactericidal effect against EPEC at 100 g/ml.
CONCLUSIONS
Results of this study, taken together with previous studies, suggest that Flaxseed possesses anti-inflammatory, antibacterial, and antispasmodic action through multiple pathways and thus offers promising potential to be developed for IBD.
PubMed: 32765633
DOI: 10.1155/2020/7974835 -
Indian Journal of Anaesthesia Apr 2020
PubMed: 32489212
DOI: 10.4103/ija.IJA_848_19 -
ELife May 2020Invasive fungal infections cause 1.6 million deaths annually, primarily in immunocompromised individuals. Mortality rates are as high as 90% due to limited treatments....
Invasive fungal infections cause 1.6 million deaths annually, primarily in immunocompromised individuals. Mortality rates are as high as 90% due to limited treatments. The azole class antifungal, fluconazole, is widely available and has multi-species activity but only inhibits growth instead of killing fungal cells, necessitating long treatments. To improve treatment, we used our novel high-throughput method, the overlap method (O2M) to identify drugs that interact with fluconazole, either increasing or decreasing efficacy. We identified 40 molecules that act synergistically (amplify activity) and 19 molecules that act antagonistically (decrease efficacy) when combined with fluconazole. We found that critical frontline beta-lactam antibiotics antagonize fluconazole activity. A promising fluconazole-synergizing anticholinergic drug, dicyclomine, increases fungal cell permeability and inhibits nutrient intake when combined with fluconazole. In vivo, this combination doubled the time-to-endpoint of mice with meningitis. Thus, our ability to rapidly identify synergistic and antagonistic drug interactions can potentially alter the patient outcomes.
Topics: Animals; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Drug Antagonism; Drug Evaluation, Preclinical; Drug Synergism; Female; Fluconazole; High-Throughput Screening Assays; Humans; Meningitis, Cryptococcal; Mice; Mycoses; Structure-Activity Relationship
PubMed: 32367801
DOI: 10.7554/eLife.54160 -
Saudi Pharmaceutical Journal : SPJ :... Mar 2020, a plant belonging to the family Lamiaceae, is endemic to Ethiopia. In Ethiopian traditional medicine, has been used for the treatment of several respiratory-related...
, a plant belonging to the family Lamiaceae, is endemic to Ethiopia. In Ethiopian traditional medicine, has been used for the treatment of several respiratory-related disorders. The present study was designed to evaluate the bronchodilatory and antimicrobial activities of leaves crude extract (Of.Cr). Ex-vivo experiments were conducted on guinea-pig trachea provided with physiological oxygenated buffer solution using emkaBath setup. The crude extract was analyzed by gas chromatography-mass spectrometry. Of.Cr, showed the presence of terpenes, fragrance components, saponins, and higher fatty acids. Of.Cr when tested on contracted tracheal chains with carbamylcholine (CCh, 1 µM) and high K (80 mM) produced relaxation by showing higher potency against CCh with incomplete inhibition of high K. Dicyclomine, used as a positive control, also showed selectively higher potency to inhibit CCh when compared with its effect against K. In the anticholinergic curves, Of.Cr at 1 mg/mL deflected CCh-induced concentration-response curves (CRCs) competitively to the right like dicyclomine (0.03 µM) and atropine whereas a higher dose of Of.Cr (3 mg/mL) produced a non-parallel shift in the CCh curves like a higher dose of dicyclomine (0.1 µM). In the calcium channel inhibitory assay, Of.Cr at 3 & 5 mg/mL, deflected CRCs of Ca to the right like verapamil, used as positive control. Of.Cr, at concentrations (1-3 mg/mL) increases cAMP levels in isolated tracheal homogenates, similar to positive control phosphodiesterase inhibitor (papaverine). When tested for antibacterial activity against standard and clinical strains, Of.Cr was found more active (MIC 475 µg/ml) against S. aureus (NCTC 6571), while the maximum inhibition (MIC 625 µg/ml) was observed by the extract when tested against MRSA. These results determine the mechanistic pathways of the observed bronchodilatory effect of with a combination of anticholinergic and dual inhibition of phosphodiesterase and voltage-gated Ca channels.
PubMed: 32194329
DOI: 10.1016/j.jsps.2020.01.007 -
Research in Pharmaceutical Sciences Oct 2019Galantamine (GAL) is a drug for treating Alzheimer's disease which has reasonable and no significant side effects. Studies have shown that GAL possesses antioxidant,...
Galantamine (GAL) is a drug for treating Alzheimer's disease which has reasonable and no significant side effects. Studies have shown that GAL possesses antioxidant, anti-inflammatory, and cholinomimetic effects that might be beneficial for inflammatory bowel disease. Therefore, this study was aimed to investigate the anti-inflammatory effect of GAL on acetic acid-induced colitis in rats. GAL at 0.25, 1.25, 2.5 mg/kg/day was administrated orally (p.o.) to different groups of male Wistar rats 2 h before induction of ulcer with acetic acid 3% and continued for 5 consecutive days. Dicyclomine (DIC) was similarly used alone (5 mg/kg/day, p.o.) or together with GAL at doses already mentioned to delineate the impact of muscarinic pathway in probable beneficial effects of GAL on colitis. Control and reference groups received distilled water (5 mL/kg, p.o.), prednisolone (4 mg/kg/day, p.o.), or mesalazine (100 mg/kg/day, p.o.) respectively. At day 6, tissue injuries were assessed for macroscopic, histopathologic, and biochemical indices of myeloperoxidase and MPO activity. Results showed that GAL at 3 applied doses, alone or in combination with DIC diminished ulcer index, total colitis index, and MPO activity as important biomarkers of colitis. DIC alone was not effective on most parameters and its concurrent administration with GAL couldn't reverse its antiulcerative effects. Prednisolone and mesalazine were both effective in this relation. The current research indicated that GAL had anti-inflammatory and antiulcerative activities independent of its muscarinic effects. Thus the antioxidant and anti-inflammatory effects may account for its anti-inflammatory and anti-ulcerative properties. Nevertheless, further detailed studies are warranted for exact elucidation of GAL mechanism on inflammation and colitis.
PubMed: 31798655
DOI: 10.4103/1735-5362.268199 -
Scientific Reports Sep 2019Memory loss is one of the most tragic symptoms of Alzheimer's disease. Our laboratory has recently demonstrated that 'i-Extract' of Ashwagandha (Withania somnifera)...
Memory loss is one of the most tragic symptoms of Alzheimer's disease. Our laboratory has recently demonstrated that 'i-Extract' of Ashwagandha (Withania somnifera) restores memory loss in scopolamine (SC)-induced mice. The prime target of i-Extract is obscure. We hypothesize that i-Extract may primarily target muscarinic subtype acetylcholine receptors that regulate memory processes. The present study elucidates key target(s) of i-Extract via cellular, biochemical, and molecular techniques in a relevant amnesia mouse model and primary hippocampal neuronal cultures. Wild type Swiss albino mice were fed i-Extract, and hippocampal cells from naïve mice were treated with i-Extract, followed by muscarinic antagonist (dicyclomine) and agonist (pilocarpine) treatments. We measured dendritic formation and growth by immunocytochemistry, kallikrein 8 (KLK8) mRNA by reverse transcription polymerase chain reaction (RT-PCR), and levels of KLK8 and microtubule-associated protein 2, c isoform (MAP2c) proteins by western blotting. We performed muscarinic receptor radioligand binding. i-Extract stimulated an increase in dendrite growth markers, KLK8 and MAP2. Scopolamine-mediated reduction was significantly reversed by i-Extract in mouse cerebral cortex and hippocampus. Our study identified muscarinic receptor as a key target of i-Extract, providing mechanistic evidence for its clinical application in neurodegenerative cognitive disorders.
Topics: Animals; Blotting, Western; Dendrites; Dicyclomine; Female; Male; Memory; Mice; Mice, Transgenic; Nerve Regeneration; Neuroprotective Agents; Pilocarpine; Plant Extracts; Receptor, Muscarinic M1; Reverse Transcriptase Polymerase Chain Reaction; Scopolamine; Withania
PubMed: 31570736
DOI: 10.1038/s41598-019-48238-6 -
The Turkish Journal of Gastroenterology... Mar 2019
Topics: Acute Disease; Dicyclomine; Female; Humans; Middle Aged; Pancreatitis
PubMed: 30459133
DOI: 10.5152/tjg.2018.18411 -
Molecules (Basel, Switzerland) Oct 2018The Emerald Ash Borer (EAB), , Fairmaire, an Asian invasive alien buprestid has devastated tens of millions of ash trees ( spp.) in North America. Foliar phytochemicals...
The Emerald Ash Borer (EAB), , Fairmaire, an Asian invasive alien buprestid has devastated tens of millions of ash trees ( spp.) in North America. Foliar phytochemicals of the genus (Oleaceae): (Green ash), (White ash), (Bush) Bush. (Pumpkin ash), Michx. (Blue ash), Marsh. (Black ash) and . (Manchurian ash) were investigated using HPLC-MS/MS and untargeted metabolomics. HPLC-MS/MS help identified 26 compounds, including phenolics, flavonoids and coumarins in varying amounts. Hydroxycoumarins, esculetin, esculin, fraxetin, fraxin, fraxidin and scopoletin were isolated from blue, black and Manchurian ashes. High-throughput metabolomics revealed 35 metabolites, including terpenes, secoiridoids and lignans. Metabolomic profiling indicated several upregulated putative compounds from Manchurian ash, especially fraxinol, ligstroside, oleuropin, matairesinol, pinoresinol glucoside, 8-hydroxypinoresinol-4-glucoside, verbenalin, hydroxytyrosol-1--glucoside, totarol and ar-artemisene. Further, dicyclomine, aphidicolin, parthenolide, famciclovir, ar-turmerone and myriocin were identified upregulated in blue ash. Principal component analysis demonstrated a clear separation between Manchurian and blue ashes from black, green, white and pumpkin ashes. The presence of defensive compounds upregulated in Manchurian ash, suggests their potential role in providing constitutive resistance to EAB, and reflects its co-evolutionary history with , where they appear to coexist in their native habitats.
Topics: Animals; Chromatography, High Pressure Liquid; Coleoptera; Coumarins; Flavonoids; Fraxinus; Metabolome; Metabolomics; Molecular Structure; Phenols; Tandem Mass Spectrometry
PubMed: 30360500
DOI: 10.3390/molecules23112734 -
The Cochrane Database of Systematic... Oct 2018Infantile colic is typically defined as full-force crying for at least three hours per day, on at least three days per week, for at least three weeks. This condition... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Infantile colic is typically defined as full-force crying for at least three hours per day, on at least three days per week, for at least three weeks. This condition appears to be more frequent in the first six weeks of life (prevalence range of 17% to 25%), depending on the specific location reported and definitions used, and it usually resolves by three months of age. The aetiopathogenesis of infantile colic is unclear but most likely multifactorial. A number of psychological, behavioural and biological components (food hypersensitivity, allergy or both; gut microflora and dysmotility) are thought to contribute to its manifestation. The role of diet as a component in infantile colic remains controversial.
OBJECTIVES
To assess the effects of dietary modifications for reducing colic in infants less than four months of age.
SEARCH METHODS
In July 2018 we searched CENTRAL, MEDLINE, Embase , 17 other databases and 2 trials registers. We also searched Google, checked and handsearched references and contacted study authors.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of dietary modifications, alone or in combination, for colicky infants younger than four months of age versus another intervention or placebo. We used specific definitions for colic, age of onset and the methods for performing the intervention. We defined 'modified diet' as any diet altered to include or exclude certain components.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcome was duration of crying, and secondary outcomes were response to intervention, frequency of crying episodes, parental/family quality of life, infant sleep duration, parental satisfaction and adverse effects.
MAIN RESULTS
We included 15 RCTs involving 1121 infants (balanced numbers of boys and girls) aged 2 to 16 weeks. All studies were small and at high risk of bias across multiple design factors (e.g. selection, attrition). The studies covered a wide range of dietary interventions, and there was limited scope for meta-analysis. Using the GRADE approach, we assessed the quality of the evidence as very low.Low-allergen maternal diet versus a diet containing known potential allergens: one study (90 infants) found that 35/47 (74%) of infants responded to a low-allergen maternal diet, compared with 16/43 (37%) of infants on a diet containing known potential allergens.Low-allergen diet or soy milk formula versus dicyclomine hydrochloride: one study (120 infants) found that 10/15 (66.6%) breastfed babies responded to dicyclomine hydrochloride, compared with 24/45 (53.3%) formula-fed babies. There was little difference in response between breastfed babies whose mother changed their diet (10/16; 62.5%) and babies who received soy milk formula (29/44; 65.9%).Hydrolysed formula versus standard formula: two studies (64 infants) found no difference in duration of crying, reported as a dichotomous outcome: risk ratio 2.03, 95% confidence interval (CI) 0.81 to 5.10; very low-quality evidence. The author of one study confirmed there were no adverse effects. One study (43 infants) reported a greater reduction in crying time postintervention with hydrolysed formula (104 min/d, 95% CI 55 to 155) than with standard formula (3 min/d, 95% CI -63 to 67).Hydrolysed formula versus another hydrolysed formula: one study (22 infants) found that two types of hydrolysed formula were equally effective in resolving symptoms for babies who commenced with standard formula (Alimentum reduced crying to 2.21 h/d (standard deviation (SD) 0.40) and Nutramigen to 2.93 h/d (SD 0.70)).Hydrolysed formula or dairy- and soy-free maternal diet versus addition of parental education or counselling: one study (21 infants) found that crying time decreased to 2.03 h/d (SD 1.03) in the hydrolysed or dairy- and soy-free group compared with 1.08 h/d (SD 0.7) in the parent education or counselling group, nine days into the intervention.Partially hydrolysed, lower lactose, whey-based formulae containing oligosaccharide versus standard formula with simethicone: one study (267 infants) found that both groups experienced a decrease in colic episodes (secondary outcome) after seven days (partially hydrolysed formula: from 5.99 episodes (SD 1.84) to 2.47 episodes (SD 1.94); standard formula: from 5.41 episodes (SD 1.88) to 3.72 episodes (SD 1.98)). After two weeks the difference between the two groups was significant (partially hydrolysed: 1.76 episodes (SD 1.60); standard formula: 3.32 episodes (SD 2.06)). The study author confirmed there were no adverse effects.Lactase enzyme supplementation versus placebo: three studies (138 infants) assessed this comparison, but none reported data amenable to analysis for any outcome. There were no adverse effects in any of the studies.Extract of Foeniculum vulgare, Matricariae recutita, and Melissa officinalis versus placebo: one study (93 infants) found that average daily crying time was lower for infants given the extract (76.9 min/d (SD 23.5), than infants given placebo (169.9 min/d (SD 23.1), at the end of the one-week study. There were no adverse effects.Soy protein-based formula versus standard cows' milk protein-based formula: one study (19 infants) reported a mean crying time of 12.7 h/week (SD 16.4) in the soy formula group versus 17.3 h/week (SD 6.9) in the standard cows' milk group, and that 5/10 (50%) responded in the soy formula group versus 0/9 (0%) in the standard cows' milk group.Soy protein formula with polysaccharide versus standard soy protein formula: one study (27 infants) assessed this comparison but did not provide disaggregated data for the number of responders in each group after treatment.No study reported on our secondary outcomes of parental or family quality of life, infant sleep duration per 24 h, or parental satisfaction.
AUTHORS' CONCLUSIONS
Currently, evidence of the effectiveness of dietary modifications for the treatment of infantile colic is sparse and at significant risk of bias. The few available studies had small sample sizes, and most had serious limitations. There were insufficient studies, thus limiting the use of meta-analysis. Benefits reported for hydrolysed formulas were inconsistent.Based on available evidence, we are unable to recommend any intervention. Future studies of single interventions, using clinically significant outcome measures, and appropriate design and power are needed.
Topics: Allergens; Colic; Crying; Diet Therapy; Female; Humans; Infant; Infant Formula; Lactase; Male; Randomized Controlled Trials as Topic; Soybean Proteins; Time Factors
PubMed: 30306546
DOI: 10.1002/14651858.CD011029.pub2