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

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

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

Studies on antihyperlipidemic and endothelium modulatory activities of polyherbal formulation (POL4) and its ingredients in high fat diet-fed rats

A compound herbal formulation (POL4) is used traditionally in interior parts (Distt. Badin) of Sindh, Pakistan, for the treatment of metabolic disorders like diabetes and hyperlipidemia. This study is aimed to determine the effectiveness of POL4 and its ingredients in hyperlipidemia and associated endothelial dysfunction and hypertension. POL4 is composed of equal proportion of Nigella sativa, Cichorium intybus, Trigonella foenum graecum and Gymnema sylvestre mixed in powdered form. Chronic (6 to 7 weeks) administration of POL4 and its ingredients mixed in diet caused a notable attenuation in total cholesterol, low density lipoprotein cholesterol, triglycerides, atherogenic index, C-reactive protein and glucose, while it has increased high density lipoprotein levels. POL4 intervention markedly (p\u3c0.01) reduced systolic blood pressure in rats to 127±1.92 vs. 145.4±1.07 mm of Hg using tail-cuff method and significantly (p\u3c0.05) improved endothelium-dependent relaxation (75±2.88 vs. 82.75±1.22%) to acetylcholine in isolated aortae of rats in treatment groups using force transducer and PowerLab system. Similar activities were assessed on the part of ingredients of POL4. These findings indicate that POL4 and its ingredients possess antihyperlipidemic, endothelium-dependent modulatory and antihypertensive activities, thus providing an evidence to the vernacular use of POL4 in hyperlipidemia and hypertension

Prevalence of obesity and overweight, its clinical markers and associated factors in a high risk South-Asian population

Background: Obesity is a global epidemic, which is a risk factor for cardiovascular diseases and metabolic abnormalities. It is measured by body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), body fat (BF) distribution and abdominal fat mass, each having its own merits and limitations. Variability in body composition between ethnic groups in South-Asians is significant and may not be truly reflected by BMI alone, which may result in misclassification. This study therefore, aims to determine the frequency of obesity, body fat composition and distribution, in a high risk population of an urban slum of Karachi, Pakistan. This survey included 451 participants selected by systematic sampling who were administered pre-tested questionnaires on socio-demographics, diet and physical activity. Chi-square was used to determine the association between categorical variables and multiple linear regression was used for quantitative variables. A P value of less than 0.05 was considered significant.Results: Classified by BMI, 29% study subjects were overweight and 21% obese (58.7% with central obesity). Body fat percent (BF%) classified 81% as overweight. Females were more obese (P 0.03) with higher prevalence of central obesity (P \u3c 0.001) and WHR (P 0.003) but with a lower muscle mass (P 0.001). Activity score and muscle mass showed inverse linear association with BF% whereas, WC, weight, BMI and WHR had a positive linear association with BF%. The relationship between BMI and BF% was quadratic with a weaker association at lower BMI. Adjusting for socio-demographic variables, BF%, weight, diastolic blood pressure (DBP), BMI and score on the diet questionnaire had a positive linear association with WC, while WC, WHR and BP had a positive linear association with BF%. BF%, muscle content and WC had a positive linear association with BMI.Conclusion: Considering lower cut-offs for South-Asians BMI and WC, this study showed a high prevalence of obesity among a sub-urban population of Karachi, which was even higher when BF% was measured. Considering the rising prevalence of non-communicable diseases, BF%, WC, WHR and BMI measurements are convenient and feasible means of identifying population at risk and hence addressing it through public awareness and early detection

Studies on the antihypertensive and antidyslipidemic activities of Viola odorata leaves extract

<p>Abstract</p> <p>Background</p> <p>This study was undertaken to provide pharmacological basis for the medicinal use of <it>Viola odorata </it>Linn. in hypertension and dyslipidemia using the <it>in vivo </it>and <it>in vitro </it>assays.</p> <p>Results</p> <p><it>Viola odorata </it>leaves extract (Vo.Cr), which tested positive for alkaloids, saponins, tannins, phenolics, coumarins and flavonoids, caused a dose-dependent (0.1-1.0 mg/kg) decrease in mean arterial blood pressure in anaesthetized rats. In isolated guinea-pig atria, Vo.Cr equally inhibited force and rate of spontaneous atrial contractions. On the baseline of rat thoracic aortae (endothelium-intact and denuded), the plant extract caused phentolamine-sensitive vasoconstriction. When tested on phenylephrine (PE, 1 μM) and K⁺(80 mM)-induced vasoconstriction, Vo.Cr caused a concentration-dependent relaxation and also caused a rightward shift of Ca⁺⁺concentration-response curves as well as suppression of PE (1 μM) control peaks in Ca⁺⁺-free medium, similar to that caused by verapamil. In the presence of L-NAME, the relaxation curve of Vo.Cr was partially inhibited showing involvement of Nitric oxide (NO) mediated pathway. In Tyloxapol-induced dyslipidemia, Vo.Cr caused reduction in total cholesterol and triglyceride levels. In high-fat diet-induced dyslipidemia model, the plant extract caused a significant decrease in total cholesterol, LDL-C, atherogenic index and prevented the increase in average body weights, while it increased HDL-C.</p> <p>Conclusions</p> <p>These data indicate that the vasodilator effect of the plant extract is mediated through multiple pathways like inhibition of Ca⁺⁺influx via membranous Ca⁺⁺channels, its release from intracellular stores and NO-mediated pathways, which possibly explain the fall in BP. The plant also showed reduction in body weight and antidyslipidemic effect which may be due to the inhibition of synthesis and absorption of lipids and antioxidant activities. Thus, this study provides a pharmacologic rationale to the medicinal use of <it>Viola odorata </it>in hypertension and dyslipidemia.</p

Studies on tracheorelaxant and anti-inflammatory activities of rhizomes of polygonatum verticillatum

Background: The present study describes the tracheorelaxant and anti-inflammatory effects of Polygonatum verticillatum which may support its medicinal use in hyperactive airway complaints and inflammatory disorders.Methods: The tracheorelaxant activity of crude extract of the rhizomes of P. verticillatum (PR) was assessed in isolated guinea-pig tracheal tissues immersed in tissue organ bath filled with Tyrode\u27s solution and a continuous supply of carbogen gas (95% O2 and 5% CO2). The contractile and relaxant responses of the tissue were measured using isometric transducers coupled with Power-Lab data acquisition system. The anti-inflammatory effect was evaluated in carrageenan-induced rat paw edema model, while the lipoxygenase inhibitory activity was performed in the in-vitro assay. Various chromatographic and spectroscopic techniques were used for the isolation and characterization of pure molecules.Results: In isolated guinea-pig tracheal preparations, PR caused complete inhibition of the high K+ (80 mM) and carbachol-induced contractions however, it was more potent against K+ than CCh, similar to verapamil. Pretreatment of the tissue with PR, displaced the Ca2+ concentration-response curves to the right, similar to that induced by verapamil, indicating the presence of Ca2+ channel blocking like activity. When tested on carrageenan-induced rat paw edema, PR demonstrated a marked reduction in edema with 65.22% protection at 200 mg/kg, similar to aspirin. In the in-vitro assay, PR showed lipoxygenase inhibitory activity (IC50: 102 ± 0.19 μg/mL), similar to baicalein. Bioactivity-guided fractionation led to the isolation of 2-hydroxybenzoic acid and β-sitosterol.Conclusions: These results indicate that the plant possesses tracheorelaxant, mediated possibly through a Ca2+ channel blockade mechanism, and anti-inflammatory activities, which may explain the medicinal use of this plant in airway disorders and inflammation

Community based lifestyle intervention for blood pressure reduction in children and young adults in developing country: cluster randomised controlled trial

Objective To assess the effectiveness of a community based lifestyle intervention on blood pressure in children and young adults in a developing country setting

Species and tissue-specificity of prokinetic, laxative and spasmodic effects of Fumaria parviflora

<p>Abstract</p> <p>Background</p> <p><it>Fumaria parviflora </it>Linn. (<it>Fumariaceae</it>), is a small branched annual herb found in many parts of the world including Saudi Arabia and Pakistan. This study was designed to provide pharmacological basis for the medicinal use of <it>Fumaria parviflora </it>in gut motility disorders.</p> <p>Methods</p> <p>The <it>in-vivo </it>prokinetic and laxative assays were conducted in mice. Isolated intestinal preparations (ileum and jejunum) from different animal species (mouse, guinea-pig and rabbit) were separately suspended in tissue baths containing Tyrode's solution bubbled with carbogen and maintained at 37°C. The spasmogenic responses were recorded using isotonic transducers coupled with PowerLab data acquisition system.</p> <p>Results</p> <p>The aqueous-methanol extract of <it>Fumaria parviflora </it>(Fp.Cr), which tested positive for the presence of alkaloids, saponins, tannins and anthraquinones showed partially atropine-sensitive prokinetic and laxative activities in the <it>in-vivo </it>in mice at 30 and 100 mg/kg. In the <it>in-vitro </it>studies, Fp.Cr (0.01-1 mg/ml) caused a concentration-dependent atropine-sensitive stimulatory effect both in mouse tissues (jejunum and ileum), and rabbit jejunum but had no effect in rabbit ileum. In guinea-pig tissues (ileum and jejunum), the crude extract showed a concentration-dependent stimulatory effect with higher efficacy in ileum and the effect was partially blocked by atropine, indicating the involvement of more than one types of gut-stimulant components (atropine-sensitive and insensitive). This could be a plausible reason for the greater efficacy of Fp.Cr in gut preparations of guinea-pig than in rabbit or mouse.</p> <p>Conclusions</p> <p>This study shows the prokinetic, laxative and spasmodic effects of the plant extract partially mediated through cholinergic pathways with species and tissue-selectivity, and provides a sound rationale for the medicinal use of <it>Fumaria parviflora </it>in gut motility disorders such as, indigestion and constipation. This study also suggests using different species to know better picture of pharmacological profile of the test material.</p