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Phytotherapy Research : PTR Sep 2014Crude extract of Lens culinaris (Lc.Cr), which tested positive for presence of anthraquinones, flavonoids, saponins, sterol, tannins, and terpenes exhibited protective...
Crude extract of Lens culinaris (Lc.Cr), which tested positive for presence of anthraquinones, flavonoids, saponins, sterol, tannins, and terpenes exhibited protective effect against castor oil-induced diarrhea in mice at 100-1000 mg/kg. In rabbit jejunum preparations, Lc.Cr caused relaxation of spontaneous contractions at 0.03-5.0 mg/mL. Lc.Cr inhibited carbachol (CCh, 1 μM) and K(+) (80 mM)-induced contractions in a pattern similar to dicyclomine, but different from verapamil and atropine. Lc.Cr shifted the Ca(++) concentration-response curves to the right, like dicyclomine and verapamil. Pretreatment of tissues with Lc.Cr (0.03-0.1 mg/mL) caused leftward shift of isoprenaline-induced inhibitory CRCs, similar to papaverine. In guinea-pig ileum, Lc.Cr produced rightward parallel shift of CCh curves, followed by non-parallel shift at higher concentration with suppression of maximum response, similar to dicyclomine, but different from verapamil and atropine. Lc.Cr (3.0-30 mg/kg) caused suppression of carbachol (CCh, 100 µg/kg)-induced increase in inspiratory pressure of anesthetized rats. In guinea-pig trachea, Lc.Cr relaxed CCh and high K(+) -induced contractions, shifted CCh curves to right and potentiated isoprenaline response. These results suggest that L. culinaris possesses antidiarrheal, antispasmodic, and bronchodilator activities mediated possibly through a combination of Ca(++) antagonist, anticholinergic, and phosphodiesterase inhibitory effects, and this study provides sound mechanistic background to its medicinal use in disorders of gut and airways hyperactivity, like diarrhea and asthma.
Topics: Animals; Antidiarrheals; Bronchodilator Agents; Female; Guinea Pigs; Ileum; In Vitro Techniques; Jejunum; Lens Plant; Male; Mice; Mice, Inbred BALB C; Parasympatholytics; Plant Extracts; Rabbits; Rats; Rats, Sprague-Dawley; Toxicity Tests, Acute; Trachea
PubMed: 24610729
DOI: 10.1002/ptr.5136 -
The Turkish Journal of Gastroenterology... Mar 2019
Topics: Acute Disease; Dicyclomine; Female; Humans; Middle Aged; Pancreatitis
PubMed: 30459133
DOI: 10.5152/tjg.2018.18411 -
Food & Function Jan 2019Theanine (γ-glutamylethylamide), an amino acid in tea, is a putative neuroprotective and antioxidant compound capable of improving lifespan and cognitive function....
Theanine (γ-glutamylethylamide), an amino acid in tea, is a putative neuroprotective and antioxidant compound capable of improving lifespan and cognitive function. Because we previously reported cognitive dysfunction in klotho mutant mice via down-regulation of janus kinase 2 (JAK2) and signal transducer and activator of transcription3 (STAT3), M1 muscarinic cholinergic receptor (M1 mAChR), and ERK signaling, we, therefore, investigated whether self-administration of theanine affects memory dysfunction in response to klotho gene depletion in mice, and whether theanine modulates the JAK2/STAT3, M1 mAChR, and ERK signaling network. Theanine significantly attenuated memory impairments in klotho mutant mice. Moreover, theanine self-administration significantly attenuated inhibitions of JAK2/STAT3 phosphorylation, M1 mAChR expression, and ERK1/2 phosphorylation in the hippocampus of klotho mutant mice. Consistently, AG490, a JAK2/STAT3 inhibitor, dicyclomine, an M1 mAChR antagonist, or U0126, an ERK1/2 inhibitor, significantly counteracted theanine-induced attenuation of memory impairment induced by klotho gene depletion in mice. Our study suggests that theanine attenuates memory impairments in a genetic aging model via up-regulation of JAK2/STAT3, M1 mAChR, and ERK signaling.
Topics: Animals; Female; Glucuronidase; Glutamates; Hippocampus; Humans; Janus Kinase 2; Klotho Proteins; Male; Memory; Memory Disorders; Mice; Mice, Knockout; STAT3 Transcription Factor
PubMed: 30574980
DOI: 10.1039/c8fo01577e -
Pediatrics Aug 2020A central tension in pediatric research ethics arises from our desire to protect children from harm while also allowing progress toward discoveries that could improve...
A central tension in pediatric research ethics arises from our desire to protect children from harm while also allowing progress toward discoveries that could improve child health. A prime example of this tension is research on a controversial yet increasingly common practice: the use of cannabis by women to treat nausea and vomiting of pregnancy. Studies of cannabis use in pregnancy face a combination of ethical hurdles because of the inclusion of pregnant women and involvement of a schedule I controlled substance. Given the growing need for research on the safety and efficacy of cannabis for nausea and vomiting of pregnancy, we reflect on the multiple historical contexts that have contributed to the challenge of studying cannabis use during pregnancy and make a case for the ethical rationale for such research.
Topics: Antiemetics; Dicyclomine; Doxylamine; Drug Approval; Drug Combinations; Ethics, Research; Female; Humans; Medical Marijuana; Morning Sickness; Ondansetron; Pediatrics; Pregnancy; Pregnant Women; Pyridoxine; Research Subjects; Teratogens; Thalidomide
PubMed: 32737240
DOI: 10.1542/peds.2020-0818R -
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 -
Indian Journal of Pharmacology 2017The study was designed to evaluate possible antihistaminic and anticholinergic activities of . (Comparative Study)
Comparative Study
OBJECTIVE
The study was designed to evaluate possible antihistaminic and anticholinergic activities of .
MATERIALS AND METHODS
Effects of crude ethanolic (Ed.Eth) and effects of crude aqueous (Ed.Aq) extracts of were studied using isolated guinea pig ileum, rabbit jejunum, and rabbit trachea. Tissue responses were recorded using isotonic and isometric transducers, connected with PowerLab data acquisition system.
RESULTS
A dose-dependent (0.1-0.3 mg/ml) rightward shift was demonstrated in histamine concentration-response curves. Whereas a complete relaxation of carbachol (1 μM)-induced contractions in isolated rabbit jejunum (3 mg/ml) and tracheal (10 mg/ml) preparations was observed, similar to dicyclomine at 1 and 3 μM, respectively. However, no significant difference between the effects of Ed.Eth and Ed.Aq was observed.
CONCLUSION
Study provides pharmacological evidence for the presence of antihistaminic and anticholinergic activities in crude extracts of and also highlight its medicinal significance in the management of airway and gastrointestinal disorders.
Topics: Animals; Cholinergic Antagonists; Dicyclomine; Dose-Response Relationship, Drug; Equisetum; Female; Guinea Pigs; Histamine Antagonists; Ileum; Jejunum; Male; Plant Extracts; Rabbits; Trachea
PubMed: 28458431
DOI: 10.4103/0253-7613.201017 -
Anti-cancer Drugs Jan 2017Recent reports on acetylcholine muscarinic receptor subtype 3 (CHRM3) have shown its growth-promoting role in prostate cancer. Additional studies report the...
Recent reports on acetylcholine muscarinic receptor subtype 3 (CHRM3) have shown its growth-promoting role in prostate cancer. Additional studies report the proliferative effect of the cholinergic agonist carbachol on prostate cancer by its agonistic action on CHRM3. This study shows that the type 1 acetylcholine muscarinic receptor (CHRM1) contributes toward the proliferation and growth of prostate cancer. We used growth and cytotoxic assays, the prostate cancer microarray database and CHRM downstream pathways' homology of CHRM subtypes to uncover multiple signals leading to the growth of prostate cancer. Growth assays showed that pilocarpine stimulates the proliferation of prostate cancer. Moreover, it shows that carbachol exerts an additional agonistic action on nicotinic cholinergic receptor of prostate cancer cells that can be blocked by tubocurarine. With the use of selective CHRM1 antagonists such as pirenzepine and dicyclomine, a considerable inhibition of proliferation of prostate cancer cell lines was observed in dose ranging from 15-60 µg/ml of dicyclomine. The microarray database of prostate cancer shows a dominant expression of CHRM1 in prostate cancer compared with other cholinergic subtypes. The bioinformatics of prostate cancer and CHRM pathways show that the downstream signalling include PIP3-AKT-CaM-mediated growth in LNCaP and PC3 cells. Our study suggests that antagonism of CHRM1 may be a potential therapeutic target against prostate cancer.
Topics: Cell Line, Tumor; Cell Proliferation; Dicyclomine; Humans; Male; Pirenzepine; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Receptor, Muscarinic M1; Receptor, Muscarinic M3; Receptors, Androgen; Signal Transduction
PubMed: 27606721
DOI: 10.1097/CAD.0000000000000432 -
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 -
Investigative Ophthalmology & Visual... Jun 2018Myopia is a refractive disorder that degrades vision. It can be treated with atropine, a muscarinic acetylcholine receptor (mAChR) antagonist, but the mechanism is...
PURPOSE
Myopia is a refractive disorder that degrades vision. It can be treated with atropine, a muscarinic acetylcholine receptor (mAChR) antagonist, but the mechanism is unknown. Atropine may block α-adrenoceptors at concentrations ≥0.1 mM, and another potent myopia-inhibiting ligand, mamba toxin-3 (MT3), binds equally well to human mAChR M4 and α1A- and α2A-adrenoceptors. We hypothesized that mAChR antagonists could inhibit myopia via α2A-adrenoceptors, rather than mAChR M4.
METHODS
Human mAChR M4 (M4), chicken mAChR M4 (cM4), or human α2A-adrenergic receptor (hADRA2A) clones were cotransfected with CRE/promoter-luciferase (CRE-Luc; agonist-induced luminescence) and Renilla luciferase (RLuc; normalizing control) into human cells. Inhibition of normalized agonist-induced luminescence by antagonists (ATR: atropine; MT3; HIM: himbacine; PRZ: pirenzepine; TRP: tropicamide; OXY: oxyphenonium; QNB: 3-quinuclidinyl benzilate; DIC: dicyclomine; MEP: mepenzolate) was measured using the Dual-Glo Luciferase Assay System.
RESULTS
Relative inhibitory potencies of mAChR antagonists at mAChR M4/cM4, from most to least potent, were QNB > OXY ≥ ATR > MEP > HIM > DIC > PRZ > TRP. MT3 was 56× less potent at cM4 than at M4. Relative potencies of mAChR antagonists at hADRA2A, from most to least potent, were MT3 > HIM > ATR > OXY > PRZ > TRP > QNB > MEP; DIC did not antagonize.
CONCLUSIONS
Muscarinic antagonists block hADRA2A signaling at concentrations comparable to those used to inhibit chick myopia (≥0.1 mM) in vivo. Relative potencies at hADRA2A, but not M4/cM4, correlate with reported abilities to inhibit chick form-deprivation myopia. mAChR antagonists might inhibit myopia via α2-adrenoceptors, instead of through the mAChR M4/cM4 receptor subtype.
Topics: Adrenergic alpha-2 Receptor Agonists; Animals; Atropine; CRISPR-Associated Protein 9; Carbachol; Chickens; Cholinergic Agonists; Clonidine; Gene Knockdown Techniques; HEK293 Cells; Humans; Ligands; Muscarinic Antagonists; Myopia; Receptor, Muscarinic M3; Receptor, Muscarinic M4; Receptors, Adrenergic, alpha-2; Receptors, Muscarinic; Transfection
PubMed: 29860464
DOI: 10.1167/iovs.17-22562 -
Drugs & Aging May 2015Inappropriate medications are often used in older adults despite their unfavourable risk-to-benefit profile. Although many of the medications in the American Geriatrics...
BACKGROUND
Inappropriate medications are often used in older adults despite their unfavourable risk-to-benefit profile. Although many of the medications in the American Geriatrics Society (AGS) Beers list are potentially inappropriate because of their anticholinergic properties, little is known regarding the nature and extent of potentially inappropriate anticholinergic medication use in older adults.
OBJECTIVES
To determine the prevalence of, and factors associated with, potentially inappropriate anticholinergic medication use in the older population.
METHODS
A retrospective, cross-sectional study was conducted, involving older adults (aged 65 years and older), using 2009-2010 Medical Expenditure Panel Survey (MEPS) data. The 2012 AGS Beers Criteria were used to define potentially inappropriate anticholinergic medications on the basis of the list of medications to avoid using in older adults irrespective of the diagnosis. Descriptive analyses were used to examine the nature and extent of potentially inappropriate anticholinergic medication use. Multivariable logistic regression within the conceptual framework of the Andersen Behavioral Model was used to identify the factors associated with potentially inappropriate anticholinergic use in older adults.
RESULTS
According to the MEPS, there were 78.60 million older adults in the USA; an estimated 7.51 million (9.56 %) of these older adults used potentially inappropriate anticholinergic medications in 2009-2010. The most frequently used potentially inappropriate anticholinergics were cyclobenzaprine, promethazine, amitriptyline, hydroxyzine and dicyclomine. Multivariable regression analyses revealed that female sex, residing in the South and the presence of anxiety disorder increased the likelihood of receiving potentially inappropriate anticholinergic medications, whereas older adults aged 75-84 or ≥ 85 years, and those with over 15 years of education, had a decreased likelihood of receiving potentially inappropriate anticholinergic medications.
CONCLUSION
The study found that approximately one in ten older adults used potentially inappropriate anticholinergic medications. Several predisposing, enabling and need factors were associated with the use of potentially inappropriate anticholinergic medications. Concerted efforts are needed to optimize potentially inappropriate anticholinergic medication use in older adults.
Topics: Aged; Aged, 80 and over; Behavior; Cholinergic Antagonists; Cross-Sectional Studies; Educational Status; Female; Geography; Health Services Needs and Demand; Health Status; Humans; Inappropriate Prescribing; Male; Models, Statistical; Prevalence; Retrospective Studies; Sex Factors; Socioeconomic Factors; United States
PubMed: 25832970
DOI: 10.1007/s40266-015-0257-x