Antispasmodic and Antidiarrheal Activities of Valeriana hardwickii Wall. Rhizome Are Putatively Mediated through Calcium Channel Blockade

Valeriana hardwickii is indigenous to Pakistan, Burma and Ceylon, where it is traditionally being used as an antispasmodic and antidiarrheal, besides its culinary use as spice. The aim of this paper was to provide pharmacological validation to these medicinal uses. The crude aqueous-methanolic extract of Valeriana hardwickii rhizome (Vh.Cr) was studied on isolated rabbit jejunum and castor oil-induced diarrhea in mice for spasmolytic and antidiarrheal properties, respectively. Vh.Cr caused concentration-dependent (0.01–1 mg/mL) relaxation of spontaneous contractions in isolated rabbit jejunum and inhibited K+-induced contractions (0.01–0.3 mg/mL), similar to verapamil, suggestive of calcium channel blockade (CCB). The CCB effect was confirmed when pretreatment of the jejunum preparations with Vh.Cr produced a concentration-dependent (0.03–0.1 mg/mL) rightward shift in the Ca++ concentration-response curves, as caused by verapamil. Vh.Cr exhibited dose-dependent (100–300 mg/kg) protection against castor oil-induced diarrhea in mice. Loperamide, a standard antidiarrheal drug, similarly prevented the diarrhea. These data indicate the presence of CCB effect in the extract of Valeriana hardwickii rhizome, possibly mediating its antispasmodic and antidiarrheal activities and provide a scientific base for its traditional use in hyperactive gut disorders

An in vivo study on the diuretic activity of Holarrhena antidysenterica

Holarrhena antidysenterica is used as diuretic in traditional medicine. The aim of this study was to evaluate the crude extract of H. antidysentrica seeds (Ha.Cr) and its fractions, n-hexane (Ha.Hx), n-butanol (Ha.Bu) and aqueous (Ha.Aq), for their diuretic effect in Wistar rats and to investigate whether the activity is concentrated in any of the fractions. Wistar rats kept on fasting for 24 h with water ad labium, divided into normal, positive control and treated groups were orally given normal saline (20 ml/kg), hydrochlorothiazide (HCT; 10 mg/kg) and different doses of the plant material, respectively. Immediately after dosing, the rats were housed in the metabolic cages. The urine was collected at 2 h interval for 6 h and volume, pH and electrolytes levels were measured. Ha.Cr caused dose-dependent (30 and 100 mg/kg) increase in urine output, indicating the diuretic effect. In addition, Ha.Cr increased urine contents of Na+ and K+, suggesting that the diuretic effect is mediated through increased electrolyte excretion. Similarly, the reference drug, HCT (10 mg/kg), increased urine volume and Na+ and K+ excretion. None of the resultant fractions exhibited diuretic effect comparable to that of the parent crude extract. Ha.Hx was devoid of diuretic effect, Ha.Bu exhibited a mild diuretic effect at 30 mg/kg, whereas, Ha.Aq caused a significant increase in urine output only at 100 mg/kg, indicating that the diuretic activity is distributed among fractions but in an order of increasing polarity of the solvent. The enhanced diuretic effect in the crude extract as compared to any individual fraction is suggestive of the existence of additive and/or synergistic effect in the crude extract. This study shows the presence of diuretic activity in the H. antidysentrica possibly mediated through its saluretic effect, which rationalizes its medicinal use as diuretic

Studies on bronchodilator and cardiac stimulant activities of Urginea indica

This study was designed to evaluate bronchodilator and cardio-tonic effects of Urginea indica to provide rational for these medicinal uses. U. indica bulb extract was studied on rabbit tracheal and guinea-pig atrial preparations mounted in tissue baths under simulated physiological conditions. U. indica inhibited carbachol (1 µM) and K+ (80 mM)-induced contractions in rabbit trachea, similar to dicyclomine, suggesting the presence of anticholinergic and calcium channel blocking (CCB) mechanisms in U. indica. Anticholinergic and CCB effects of U. indica were respectively confirmed when it shifted the carbachol and Ca2+ concentration-response curves rightwards, similar to dicyclomine. U. indica (0.01-1 mg/mL) increased force of guinea-pig atrial contractions without significantly affecting the rate. These data, indicating that U. indica possesses the bronchodilator activity possibly mediated through a combination of anticholinergic and Ca2+ antagonist mechanisms together with selective positive inotropic effect, provide rational for medicinal applications of U. indica in airways and cardiac disorders

Readiness of Curriculum for Peace Education; Analysis of Urdu

Every society develops the curriculum with the expectation to fulfill its needs. Peace is a need of every human society from the beginning. This research is conducted to analyze the readiness of Urdu curriculum for this need of peace. The analysis was conducted by adopting the core curriculum analysis framework suggested by Levander & Mikkola, in 2009. The analysis was accomplished in two stages: Concept mapping framework and dimensional description framework. At first a tool of concept map consisted of list of aspects of peace education was developed. Urdu curriculum objectives, textbooks and activities suggested in the textbooks of 6th, 7th and 8th grade was analyzed for the aspects of peace education. Text description that was noted down in concept map was further analyzed to explore the quality of description. Reliability of data was maintained by applying expert peer reliability. Peace education is not adequately addressed in the objectives of curriculum of Urdu at elementary level. Text books of Urdu for grade 6th, 7th and 8th elaborated few aspects of peace education e.g. love for humanity, human value, brotherhood, tolerance, critical thinking, cultural diversity, gender equality, creativity and environmental education. Dimension of description in aspects of peace education were found brief most of the time. The study suggests that all aspects of peace education in curriculum of Urdu should be included in a balance form. Existing curriculum of Urdu for elementary grades should be revised to promote peace education

Antiurolithic activity of Origanum vulgare is mediated through multiple pathways

<p>Abstract</p> <p>Background</p> <p><it>Origanum vulgare </it>Linn has traditionally been used in the treatment of urolithiasis. Therefore, we investigated the crude extract of <it>Origanum vulgare </it>for possible antiurolithic effect, to rationalize its medicinal use.</p> <p>Methods</p> <p>The crude aqueous-methanolic extract of <it>Origanum vulgare </it>(Ov.Cr) was studied using the <it>in vitro </it>and <it>in vivo </it>methods. In the <it>in vitro </it>experiments, supersaturated solution of calcium and oxalate, kidney epithelial cell lines (MDCK) and urinary bladder of rabbits were used, whereas, in the <it>in vivo </it>studies, rat model of urolithiasis was used for the study of preventive and curative effect.</p> <p>Results</p> <p>In the <it>in vitro </it>experiments, Ov.Cr exhibited a concentration-dependent (0.25-4 mg/ml) inhibitory effect on the slope of nucleation and aggregation and also decreased the number of calcium oxalate monohydrate crystals (COM) produced in calcium oxalate metastable solutions. It also showed concentration-dependent antioxidant effect against DPPH free radical and lipid peroxidation induced in rat kidney tissue homogenate. Ov.Cr reduced the cell toxicity using MTT assay and LDH release in renal epithelial cells (MDCK) exposed to oxalate (0.5 mM) and COM (66 μg/cm²) crystals. Ov.Cr relaxed high K⁺(80 mM) induced contraction in rabbit urinary bladder strips, and shifted the calcium concentration-response curves (CRCs) towards right with suppression of the maximum response similar to that of verapamil, a standard calcium channel blocker. In male Wistar rats receiving lithogenic treatment comprising of 0.75% ethylene glycol in drinking water given for 3 weeks along with ammonium chloride (NH₄Cl) for the first 5 days, Ov.Cr treatment (10-30 mg/kg) prevented as well as reversed toxic changes including loss of body weight, polyurea, crystalluria, oxaluria, raised serum urea and creatinine levels and crystal deposition in kidneys compared to their respective controls.</p> <p>Conclusion</p> <p>These data indicating the antiurolithic activity in Ov.Cr, possibly mediated through inhibition of CaOx crystallization, antioxidant, renal epithelial cell protective and antispasmodic activities, rationalizes its medicinal use in urolithiasis.</p

Ethnopharmacological studies on chrozophora prostrata in perspective of its folkloric reputation as purgative

This study was undertaken to validate the medicinal use of Chrozophora prostrata in constipation. The crude extract of C prostrata produced laxative effect in mice at 100 and 300 mg/kg, similar to carbachol and castor oil. In spontaneously contracting rabbit jejunum tissues, C. prostrata (0.01-3 mg/mL) exhibited atropine-sensitive spasmogenic effect, which was reproducible in guinea-pig ileum. Interestingly, at high concentrations, C. prostrata showed concentration-dependent inhibitory effect on rabbit jejunum, suggesting the presence of accompanied spasmolytic activity. When tested on induced contractions, C. prostrata completely relaxed low K+-induced contraction, while partially inhibited high K+, similar to cromakalim. Tetraethylammonium pretreatment abolished the relaxant effect of C. prostrata on low K+-induced contractions while glibenclamide caused partial inhibition, suggesting the involvement of some non-specific and ATP-dependent K+ channels. These data show that C. prostrata possesses laxative effect at low doses mediated through cholinergic action followed by the spasmolytic activity at high doses mediated possibly through K+ channel activation

Multiple mechanisms of flaxseed: Effectiveness in inflammatory bowel disease

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 in vitro 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 µg/ml) was bactericidal against enteropathogenic E.coli (EPEC), enterotoxigenic E.coli (ETEC), and enteroaggregative E.coli (EAEC), whereas Fs.Cr exhibited bactericidal effect against EPEC at 100 µg/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

Metabolic profiling of pre-gestational and gestational diabetes mellitus identifies novel predictors of pre-term delivery.

Pregnant women with gestational diabetes mellitus (GDM) or type 2 diabetes mellitus (T2DM) are at increased risks of pre-term labor, hypertension and preeclampsia. In this study, metabolic profiling of blood samples collected from GDM, T2DM and control pregnant women was undertaken to identify potential diagnostic biomarkers in GDM/T2DM and compared to pregnancy outcome. Sixty-seven pregnant women (21 controls, 32 GDM, 14 T2DM) in their second trimester underwent targeted metabolomics of plasma samples using tandem mass spectrometry with the Biocrates MxP Quant 500 Kit. Linear regression models were used to identify the metabolic signature of GDM and T2DM, followed by generalized linear model (GLMNET) and Receiver Operating Characteristic (ROC) analysis to determine best predictors of GDM, T2DM and pre-term labor. The gestational age at delivery was 2 weeks earlier in T2DM compared to GDM and controls and correlated negatively with maternal HbA1C and systolic blood pressure and positively with serum albumin. Linear regression models revealed elevated glutamate and branched chain amino acids in GDM + T2DM group compared to controls. Regression models also revealed association of lower levels of triacylglycerols and diacylglycerols containing oleic and linoleic fatty acids with pre-term delivery. A generalized linear model ROC analyses revealed that that glutamate is the best predictors of GDM compared to controls (area under curve; AUC = 0.81). The model also revealed that phosphatidylcholine diacyl C40:2, arachidonic acid, glycochenodeoxycholic acid, and phosphatidylcholine acyl-alkyl C34:3 are the best predictors of GDM + T2DM compared to controls (AUC = 0.90). The model also revealed that the triacylglycerols C17:2/36:4 and C18:1/34:1 are the best predictors of pre-term delivery (≤ 37 weeks) (AUC = 0.84). This study highlights the metabolite alterations in women in their second trimester with diabetes mellitus and identifies predictive indicators of pre-term delivery. Future studies to confirm these associations in other cohorts and investigate their functional relevance and potential utilization for targeted therapies are warranted.This research was sponsored by QNRF, Grant no. NPRP10-1205-160010 (NAM)

Prevalence of newly detected diabetes in pregnancy in Qatar, using universal screening.

Diabetes first detected during pregnancy is currently divided into gestational diabetes mellitus (GDM) and diabetes mellitus (DM)- most of which are type 2 DM (T2DM). This study aims to define the prevalence and outcomes of diabetes first detected in pregnancy based on 75-gram oral glucose tolerance test (OGTT)using the recent WHO/IADPSG guidelines in a high-risk population. This is a retrospective study that included all patients who underwent a 75 g (OGTT) between Jan 2016 and Apr 2016 and excluded patients with known pre-conception diabetes. The overall prevalence of newly detected diabetes in pregnancy among the 2000 patients who fulfilled the inclusion/exclusion criteria was 24.0% (95% CI 22.1-25.9) of which T2DM was 2.5% (95% CI 1.9-3.3), and GDM was 21.5% (95% CI 19.7-23.3). The prevalence of newly detected diabetes in pregnancy was similar among the different ethnic groups. The T2DM group was older (mean age in years was 34 ±5.7 vs 31.7±5.7 vs 29.7 ±5.7, p<0.001); and has a higher mean BMI (32.4±6.4 kg/m2 vs 31.7±6.2 kg/m2 vs 29.7± 6.2 kg/m2, p< 0.01) than the GDM and the non-DM groups, respectively. The frequency of pre-eclampsia, pre-term delivery, Caesarean-section, macrosomia, LGA and neonatal ICU admissions were significantly higher in the T2DM group compared to GDM and non-DM groups. Diabetes first detected in pregnancy is equally prevalent among the various ethnic groups residing in Qatar. Newly detected T2DM carries a higher risk of poor pregnancy outcomes; stressing the importance of proper classification of cases of newly detected diabetes in pregnancy.The authors received no specific funding for this wor

apoA2 correlates to gestational age with decreased apolipoproteins A2, C1, C3 and E in gestational diabetes.

Pregnant women with gestational diabetes mellitus (GDM) are at risk of adverse outcomes, including gestational hypertension, pre-eclampsia, and preterm delivery. This study was undertaken to determine if apolipoprotein (apo) levels differed between pregnant women with and without GDM and if they were associated with adverse pregnancy outcome. Pregnant women (46 women with GDM and 26 women without diabetes (ND)) in their second trimester were enrolled in the study. Plasma apos were measured and correlated to demographic, biochemical, and pregnancy outcome data. apoA2, apoC1, apoC3 and apoE were lower in women with GDM compared with control women (p=0.0019, p=0.0031, p=0.0002 and p=0.015, respectively). apoA1, apoB, apoD, apoH, and apoJ levels did not differ between control women and women with GDM. Pearson bivariate analysis revealed significant correlations between gestational age at delivery and apoA2 for women with GDM and control women, and between apoA2 and apoC3 concentrations and C reactive protein (CRP) as a measure of inflammation for the whole group. Apoproteins apoA2, apoC1, apoC3 and apoE are decreased in women with GDM and may have a role in inflammation, as apoA2 and C3 correlated with CRP. The fact that apoA2 correlated with gestational age at delivery in both control women and women with GDM raises the hypothesis that apoA2 may be used as a biomarker of premature delivery, and this warrants further investigation