Arif-ullah Khan

Gastrointestinal, selective airways and urinary bladder relaxant effects of Hyoscyamus niger are mediated through dual blockade of muscarinic receptors and Ca2+ channels.

This study describes the spasmolytic, antidiarrhoeal, antisecretory, bronchodilatory and urinary bladder relaxant properties of Hyoscyamus niger to rationalize some of its medicinal uses. The crude extract of H. niger seeds (Hn.Cr) caused a complete concentration‐dependent relaxation of spontaneous contractions of rabbit jejunum, similar to that caused by verapamil, whereas atropine produced partial inhibition. Hn.Cr inhibited contractions induced by carbachol (1 μm) and K+ (80 mm) in a pattern similar to that of dicyclomine, but different from verapamil and atropine. Hn.Cr shifted the Ca2+ concentration–response curves to the right, similar to that caused by verapamil and dicyclomine, suggesting a Ca2+ channel‐blocking mechanism in addition to an anticholinergic effect. In the guinea‐pig ileum, Hn.Cr produced a rightward parallel shift of the acetylcholine curves, followed by a non‐parallel shift with suppression of the maximum response at a higher concentration, similar to that caused by dicyclomine, but different from that of verapamil and atropine. Hn.Cr exhibited antidiarrhoeal and antisecretory effects against castor oil‐induced diarrhoea and intestinal fluid accumulation in mice. In guinea‐pig trachea and rabbit urinary bladder tissues, Hn.Cr caused relaxation of carbachol (1 μm) and K+ (80 mm) induced contractions at around 10 and 25 times lower concentrations than in gut, respectively, and shifted carbachol curves to the right. Only the organic fractions of the extract had a Ca2+ antagonist effect, whereas both organic and aqueous fractions had anticholinergic effect. A constituent, β‐sitosterol exhibited Ca2+ channel‐blocking action. These results suggest that the antispasmodic effect of H. niger is mediated through a combination of anticholinergic and Ca2+ antagonist mechanisms. The relaxant effects of Hn.Cr occur at much lower concentrations in the trachea and bladder. This study offers explanations for the medicinal use of H. niger in treating gastrointestinal and respiratory disorders and bladder hyperactivity.

Antispasmodic and bronchodilator activities of Artemisia vulgaris are mediated through dual blockade of muscarinic receptors and calcium influx.

AIM OF THE STUDY The present study describes antispasmodic, antidiarrheal, bronchodilatory and tracheo-relaxant activities of Artemisia vulgaris to rationalize some of its traditional uses. MATERIALS AND METHODS Crude extract of Artemisia vulgaris (Av.Cr) was studied in the isolated tissue preparations of rabbit jejunum and guinea-pig trachea, as well as in the in vivo castor oil-induced diarrhea and bronchodilatory techniques. RESULTS Av.Cr which tested positive for alkaloids, coumarins, flavonoids, saponins, sterols, tannins and terpenes caused concentration-dependent (0.03-10mg/mL) relaxation of jejunum spontaneous contractions. Av.Cr inhibited the carbachol (CCh, 1 microM) and K(+) (80 mM)-induced contractions in a pattern, similar to that of dicyclomine. Av.Cr shifted the Ca(2+) concentration-response curves to right, like that caused by verapamil and dicyclomine. Av.Cr produced rightward parallel shift in CCh-curves, followed by non-parallel shift at higher concentration with the suppression of the maximum response, similar to that caused by dicyclomine. It exhibited protective effect against castor oil-induced diarrhea and CCh-mediated bronchoconstriction in rodents. In trachea, Av.Cr relaxed the CCh (1 microM) and K(+) (80 mM)-induced contractions and shifted the CCh-curves to right. CONCLUSION These results indicate that Artemisia vulgaris exhibits combination of anticholinergic and Ca(2+) antagonist mechanisms, which provides pharmacological basis for its folkloric use in the hyperactive gut and airways disorders, such as abdominal colic, diarrhea and asthma.

Blood pressure lowering effect of olive is mediated through calcium channel blockade

Olive (Olea europea) is used in traditional medicine as a remedy for hypertension. The aqueous–methanolic crude extract of O. europea fruit (OeF.Cr) was studied in anaesthetized rats and its possible mechanism was elucidated using isolated cardiovascular preparations. Intravenous administration of OeF.Cr produced a dose-dependent (30–100 mg/kg) fall in arterial blood pressure in normotensive anaesthetized rats. This effect remained unaltered in atropinized animals. In the in vitro studies OeF.Cr (0.1–3.0 mg/ml) inhibited spontaneously beating guinea-pig atria. Moreover, it relaxed K+ and/or phenylephrine-induced contractions of rabbit aortic preparations over a dose range of 0.1–3.0 mg/ml, suggesting calcium channel blockade (CCB). The CCB effect was confirmed when pretreatment of the vascular preparations with OeF.Cr produced a dose-dependent rightward shift of the Ca2 +  dose–response curves, similar to verapamil. These results suggest that the blood pressure lowering effect of olive is mediated through CCB, justifying its use in hypertension.

Mechanisms underlying the antispasmodic and bronchodilatory properties of Terminalia bellerica fruit

AIM OF THE STUDY The present investigation was carried out to provide the pharmacological basis for the medicinal use of Terminalia bellerica in hyperactive gastrointestinal and respiratory disorders. MATERIALS AND METHODS Crude extract of Terminalia bellerica fruit (Tb.Cr) was studied in in vitro and in vivo. RESULTS Tb.Cr caused relaxation of spontaneous contractions in isolated rabbit jejunum at 0.1-3.0mg/mL. Tb.Cr inhibited the carbachol (CCh, 1microM) and K(+) (80mM)-induced contractions in a pattern similar to that of dicyclomine, but different from nifedipine and atropine. Tb.Cr shifted the Ca(++) concentration-response curves to right, like nifedipine and dicyclomine. In guinea-pig ileum, Tb.Cr produced rightward parallel shift of acetylcholine-curves, followed by non-parallel shift at higher concentration with the suppression of maximum response, similar to dicyclomine, but different from nifedipine and atropine. Tb.Cr exhibited protective effect against castor oil-induced diarrhea and carbachol-mediated bronchoconstriction in rodents. In guinea-pig trachea, Tb.Cr relaxed the CCh-induced contractions, shifted CCh-curves to right and inhibited the contractions of K(+). Anticholinergic effect was distributed both in organic and aqueous fractions, while CCB was present in the aqueous fraction. CONCLUSIONS These results indicate that Terminalia bellerica fruit possess a combination of anticholinergic and Ca(++) antagonist effects, which explain its folkloric use in the colic, diarrhea and asthma.

Antispasmodic and bronchodilator activities of St John's wort are putatively mediated through dual inhibition of calcium influx and phosphodiesterase

The crude extract of aerial parts of St Johns wort (Hypericum perforatum) (Hp.Cr) and its fractions were studied in vitro for its possible spasmolytic and bronchodilator activities to rationalize some of its medicinal uses. In rabbit jejunum preparations, Hp.Cr caused a concentration‐dependent relaxation of both spontaneous and K+ (80 mm)‐induced contractions at a similar concentration range (0.1–1.0 mg/mL), similar to that produced by papaverine, whereas verapamil was relatively potent against K+‐induced contractions. Hp.Cr shifted the Ca2+ concentration–response curves (CRCs) to the right, similar to that caused by papaverine or verapamil and also caused leftward shift of isoprenaline‐induced inhibitory CRCs, similar to papaverine. In guinea‐pig tracheal preparations, Hp.Cr caused relaxation of carbachol and K+‐induced contractions at similar concentrations (0.01–0.3 mg/mL) and also shifted the isoprenaline‐induced inhibitory CRCs to the left, similar to that caused by papaverine. In rabbit aorta preparations at rest, Hp.Cr produced a moderate vasoconstriction, while exhibited vasodilator effect against phenylephrine and K+‐induced contractions. Papaverine and verapamil also produced similar non‐specific vasodilation, but were devoid of any vasoconstrictor effect. Hp.Cr caused suppression of atrial force of contractions at concentrations about 20 times higher than those that produced inhibitory effect in smooth muscle preparations, similar to papaverine. These results suggest that the spasmolytic effects of Hp.Cr are mediated through dual inhibition of calcium influx and phosphodiesterase (PDE)‐like mechanisms, which might explain the medicinal use of St Johns wort in the disorders of gastrointestinal and respiratory tracts. Furthermore, the presence of Ca2+ antagonist and PDE inhibitory‐like constituents might also be contributing to some extent in the well established use of plant in depression.

Prevalence and correlates of smoking on the roof of the world

OBJECTIVE To determine the prevalence and correlates of cigarette smoking among adults in high mountain rural areas of northern Pakistan. DESIGN Cross sectional survey. PARTICIPANTS A sample of 4203 adults (aged 18 years and over) were selected by stratified random sampling from 16 villages. MAIN OUTCOME MEASURE Self reported smoking prevalence; age of smoking initiation; daily cigarette consumption and association between current smoking and sociodemographic variables, use of snuff, wine, body mass index, blood pressure, family history of stroke, and hypertension. RESULTS 614/1406 men (43.7%) and 154/2797 (5.5%) women reported smoking cigarettes. The age standardised prevalence of smoking was 40.5% for men and 6.3% for women. Men were more likely (odds ratio (OR) 6.5, 95% confidence interval (CI) 4.75 to 8.79) to be smokers. Smokers were more likely to use snuff (OR 1.39, 95% CI 1.12 to 1.73), drink wine (OR 3.47, 95% CI 2.81 to 4.29), and were more likely to work as farmers (OR 1.55, 95% CI 1.05 to 2.29) or shopkeepers (OR 2.63, 95% CI 1.67 to 4.14). Individuals with college level education and with desirable body mass index were less likely to smoke (OR 0.55, 95% CI 0.35 to 0.87; OR 0.74, 95% CI 0.57 to 0.96). CONCLUSION Cigarette smoking is a major public health problem in this high mountain community of Pakistan, particularly among the male population, the majority of whom begin to smoke quite early in life. A comprehensive tobacco control effort incorporated into the existing community based health infrastructure is needed.

Pharmacological Basis for the Medicinal Use of Lepidium sativum in Airways Disorders

Lepidium sativum is widely used in folk medicine for treatment of hyperactive airways disorders, such as asthma, bronchitis and cough. The crude extract of Lepidium sativum (Ls.Cr) inhibited carbachol (CCh, 1 μM-) and K+ (80 mM-) induced contractions in a pattern similar to that of dicyclomine. Ls.Cr at 0.03 mg/mL produced a rightward parallel shift of CCh curves, followed by nonparallel shift at higher concentration (0.1 mg/mL), suppressing maximum response, similar to that caused by dicyclomine. Pretreatment of tissues with Ls.Cr (0.1–0.3 mg/mL) shifted Ca++ concentration-response curves (CRCs) to right, as produced by verapamil. Ls.Cr at low concentrations (0.03–0.1 mg/mL) caused leftward shift of isoprenaline-induced inhibitory CRCs, like that caused by rolipram, a phosphodiesterase (PDE) inhibitor. These results indicate that bronchodilatory effect of Lepidium sativum is mediated through a combination of anticholinergic, Ca++ antagonist and PDE inhibitory pathways, which provides sound mechanistic background for its medicinal use in the overactive airways disorders.

Blood Pressure Lowering, Cardiovascular Inhibitory and Bronchodilatory Actions of Achillea millefolium

Achillea millefolium Linn. (Asteraceae) is used in folk medicine for the treatment of overactive cardiovascular and respiratory ailments. This study describes its hypotensive, cardio‐depressant, vasodilatory and bronchodilatory activities. The crude extract of Achillea millefolium (Am.Cr) caused a dose‐dependent (1–100 mg/kg) fall in arterial blood pressure of rats under anaesthesia. In spontaneously beating guinea‐pig atrial tissues, Am.Cr exhibited negative inotropic and chronotropic effects. In isolated rabbit aortic rings, Am.Cr at 0.3–10 mg/mL relaxed phenylephrine (PE, 1 µm) and high K+ (80 mm)‐induced contractions, as well as suppressed the PE (1 µm) control peaks obtained in Ca++‐free medium, like that caused by verapamil. The vasodilator effect of Am.Cr was partially blocked by Nω‐nitro‐l‐arginine methyl ester in endothelium intact preparations. In guinea‐pig tracheal strips, Am.Cr inhibited carbachol (CCh, 1 µm) and K+‐induced contractions. These results indicate that Achillea millefolium exhibits hypotensive, cardiovascular inhibitory and bronchodilatory effects, thus explaining its medicinal use in hyperactive cardiovascular and airway disorders, such as hypertension and asthma. Copyright

Pharmacological Basis for the Medicinal Use of Zanthoxylum armatum in Gut, Airways and Cardiovascular Disorders

This study describes the gut, airways and cardiovascular modulatory activities of Zanthoxylum armatum DC. (Rutaceae) to rationalize some of its medicinal uses. The crude extract of Zanthoxylum armatum (Za.Cr) caused concentration‐dependent relaxation of spontaneous and high K+ (80 mM)‐induced contractions in isolated rabbit jejunum, being more effective against K+ and suggestive of Ca++ antagonist effect, which was confirmed when pretreatment of the tissues with Za.Cr shifted Ca++ concentration‐response curves to the right, like that caused by verapamil. Za.Cr inhibited the castor‐oil‐induced diarrhea in mice at 300–1000 mg/kg. In rabbit tracheal preparations, Za.Cr relaxed the carbachol (1 μM) and high K+‐induced contractions, in a pattern similar to that of verapamil. In isolated rabbit aortic rings, Za.Cr exhibited vasodilator effect against phenylephrine (1 μM) and K+‐induced contractions. When tested in guinea pig atria, Za.Cr caused inhibition of both atrial force and rate of spontaneous contractions, like that caused by verapamil. These results indicate that Zanthoxylum armatum exhibits spasmolytic effects, mediated possibly through Ca++ antagonist mechanism, which provides pharmacological base for its medicinal use in the gastrointestinal, respiratory and cardiovascular disorders. Copyright

Pharmacological basis for the medicinal use of Holarrhena antidysenterica in gut motility disorders.

Context: Holarrhena antidysenterica Wall. (Apocynaceae) is widely used in traditional medical system for treatment of constipation, colic, and diarrhea. Aim: This study was carried out to provide pharmacological basis for medicinal use of Holarrhena antidysenterica in gastrointestinal disorders. Materials and methods: Hydro-ethanolic crude extract of Holarrhena antidysenterica (HaCE) and its fractions were studied in various gastrointestinal isolated tissue preparations. Results: In guinea pig ileum tissues, HaCE at 0.3-10 mg/mL caused pyrilamine-sensitive spasmogenic effect. When tested in spontaneously contracting rabbit jejunum preparations, HaCE (0.01-3.0 mg/mL) caused moderate stimulation, followed by a relaxant effect at next higher concentrations. In presence of pyrilamine, the contractile effect was blocked and the relaxation was observed at lower concentrations (0.01-0.3 mg/mL). HaCE inhibited the high K+ (80 mM)-induced contractions at concentration range of 0.01-1.0 mg/mL and shifted Ca++ concentration response curves to the right, like that caused by verapamil. Activity-directed fractionation revealed that the spasmogenic component was concentrated in the aqueous fraction, while the spasmolytic component was concentrated in the organic fraction. Discussion and conclusion: These results indicate that the gut stimulant and relaxant activities of Holarrhena antidysenterica are mediated possibly through activation of histamine receptors and Ca++ channel blockade, respectively and this study provides sound mechanistic background for its usefulness in gut motility disorders such as constipation, colic, and possibly diarrhea.