Studies on Cardio-suppressant, Vasodilator and Tracheal Relaxant Effects of Sarcococca saligna

Ghayur, Muhammad Nabeel,Gilani, Anwarul Hassan The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.11

Sarcococca saligna is a shrub that is traditionally used for its medicinal properties in Pakistan. In this study we report the cardio-suppressant, vasodilator and tracheal relaxant activities of the aqueous-methanolic extract (Ss.Cr) of the plant. Ss.Cr, that tested positive for the presence of saponins, flavonoids, tannins, phenols, and alkaloids, exhibited a dose-dependent (0.3-5 mg/mL) negative inotropic and chronotropic effect on the isolated guinea-pig atrium which was resistant to atropine ($1\;{\mu}M$) and aminophylline ($10\;{\mu}M$) pretreatment. In rabbit thoracic aorta, Ss.Cr dose-dependently (0.1-3 mg/mL) relaxed the high $K^{+}$ (80 mM) and phenylephrine ($PE,\;1\;{\mu}M$)-induced contractions, indicating a possible $Ca^{++}$ channel blocking (CCB) effect. When tested against PE ($1\;{\mu}M$) control peaks in normal $Ca^{++}\;and\;Ca^{++}$-free Kreb's solution, Ss.Cr exhibited dose-dependent (0.1-3 mg/mL) inhibition, being more potent in relaxing the PE responses in $Ca^{++}$-free Kreb's solution, thus indicating specific blockade of $Ca^{++}$ release from the intracellular stores. Ss.Cr also relaxed the agonist-induced contractions in: a) rat aorta irrespective of the presence of endothelium or nitric oxide synthase inhibitor L-NAME and b) rabbit and guinea-pig tracheal strips. The data shows that Ss.Cr possesses possible $Ca^{++}$ channel blocking activity which might be responsible for its observed cardio-suppressant, vasodilator and tracheal relaxant effects though more tests are required to confirm this $Ca^{++}$ channel blocking effect.

Antispasmodic, Bronchodilator and Vasodilator Activities of (+)-Catechin, a Naturally Occurring Flavonoid

Ghayur, Muhammad Nabeel,Khan, Hassan,Gilani, Anwarul Hassan 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.8

Catechin is a well-known flavonoid found in many food plants and often utilized by naturopaths for the symptomatic treatment of several gastrointestinal, respiratory and vascular diseases. Our aim was to explore the biological basis for the medicinal use of this flavonoid by investigating whether catechin exhibits any pharmacological activity on smooth muscle preparations. We found that catechin dose-dependently relaxes both spontaneous and high $K^{+}$ (80 mM)-induced contraction in rabbit jejunum, showing specificity for the latter by causing a rightward shift in the $Ca^{2+}$ dose-response curve. Similar results were observed with verapamil, a standard $Ca^{2+}$ channel blocker (CCB). Catechin also inhibited high $K^{+}$-induced contraction in intact smooth muscle preparations from rat stomach fundus, guinea-pig ileum and guinea-pig trachea. In rat aorta, catechin inhibited phenylephrine (PE, 1 ${\mu}M$) and $K^{+}$-induced contractions in a similar fashion. In PE-contracted, endothelium-intact aorta, this vasodilator effect was partially blocked by $N_{\grave{u}}$-nitro-L-arginine methyl ester and atropine, indicating activity at cholinergic receptors and possibly a CCB effect at higher doses of catechin. In guinea-pig atria catechin was found inactive. These data suggest that catechin may possess $Ca^{2+}$ antagonist activity - in addition to an endothelium-dependent relaxant component in blood vessels - thus providing a pharmacological basis for the efficacy of catechin in hyperexcitability disorders of gastrointestinal, respiratory and vascular smooth muscle.

Studies on Cardio-suppressant, Vasodilator and Tracheal Relaxant Effects of Sarcococca saligna

Muhammad Nabeel Ghayur,Anwarul Hassan Gilani 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.11

Sarcococca saligna is a shrub that is traditionally used for its medicinal properties in Pakistan. In this study we report the cardio-suppressant, vasodilator and tracheal relaxant activities of the aqueous-methanolic extract (Ss.Cr) of the plant. Ss.Cr, that tested positive for the presence of saponins, flavonoids, tannins, phenols, and alkaloids, exhibited a dose-dependent (0.3-5 mg/mL) negative inotropic and chronotropic effect on the isolated guinea-pig atrium which was resistant to atropine (1 μM) and aminophylline (10 μM) pretreatment. In rabbit thoracic aorta, Ss.Cr dose-dependently (0.1-3 mg/mL) relaxed the high K+ (80 mM) and phenylephrine (PE, 1 μM)-induced contractions, indicating a possible Ca++ channel blocking (CCB) effect. When tested against PE (1 μM) control peaks in normal Ca++ and Ca++-free Kreb’s solution, Ss.Cr exhibited dose-dependent (0.1-3 mg/mL) inhibition, being more potent in relaxing the PE responses in Ca++-free Kreb’s solution, thus indicating specific blockade of Ca++ release from the intracellular stores. Ss.Cr also relaxed the agonist-induced contractions in: a) rat aorta irrespective of the presence of endothelium or nitric oxide synthase inhibitor L-NAME and b) rabbit and guinea-pig tracheal strips. The data shows that Ss.Cr possesses possible Ca++ channel blocking activity which might be responsible for its observed cardio-suppressant, vasodilator and tracheal relaxant effects though more tests are required to confirm this Ca++ channel blocking effect.

Antispasmodic, Bronchodilator and Vasodilator Activities of (+)-Catechin, a Naturally Occurring Flavonoid

Muhammad Nabeel Ghayur,Hassan Khan,Anwarul Hassan Gilani 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.8

Catechin is a well-known flavonoid found in many food plants and often utilized by naturopaths for the symptomatic treatment of several gastrointestinal, respiratory and vascular diseases. Our aim was to explore the biological basis for the medicinal use of this flavonoid by investigating whether catechin exhibits any pharmacological activity on smooth muscle preparations. We found that catechin dose-dependently relaxes both spontaneous and high K+ (80 mM)-induced contraction in rabbit jejunum, showing specificity for the latter by causing a rightward shift in the Ca2+ dose-response curve. Similar results were observed with verapamil, a standard Ca2+ channel blocker (CCB). Catechin also inhibited high K+-induced contraction in intact smooth muscle preparations from rat stomach fundus, guinea-pig ileum and guinea-pig trachea. In rat aorta, catechin inhibited phenylephrine (PE, 1 μM) and K+-induced contractions in a similar fashion. In PE-contracted, endothelium-intact aorta, this vasodilator effect was partially blocked by Nù-nitro-L-arginine methyl ester and atropine, indicating activity at cholinergic receptors and possibly a CCB effect at higher doses of catechin. In guinea-pig atria catechin was found inactive. These data suggest that catechin may possess Ca2+ antagonist activity - in addition to an endothelium-dependent relaxant component in blood vessels - thus providing a pharmacological basis for the efficacy of catechin in hyperexcitability disorders of gastrointestinal, respiratory and vascular smooth muscle.

Synthesis and Smooth Muscle-Selective Relaxant Activity of a Piperidine Analogue: 1-(4'-Fluorophenacyl)-4-Hydroxy-4-Phenyl-Piperidinium Chloride

Taqvi, Syed Intasar Hussain,Ghayur, Muhammad Nabeel,Gilani, Anwarul Hassan,Saify, Zafar Saeed,Aftab, Mohammad Tariq The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.1

The antispasmodic and vasodilator activities of a newly synthesized piperidine derivative (1-(4'fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride) were studied in vitro. The test compound exhibited a dose-dependent relaxant effect on the spontaneous and $K^+$ (75 mM)-induced contractions of isolated rabbit jejunum with respective $EC_{50}$ values of 0.01 mM(0.01-0.02, 95% CI) and 0.30 mM (0.17-0.56). The $Ca^{++}$ channel blocking (CCB) activity was confirmed when the test compound (0.1-0.2 mM) shifted the $Ca^{++}$ dose-response curves to the right, similar to that produced by verapamil ($0.1-1.0{\mu}M$), a standard CCB. In the isolated rabbit aorta, the test compound showed a dose-dependent vasodilator effect on $K^+$ (75 mM)-induced contractions with an $EC_{50}$ value of 0.08 mM (0.02-0.26) while also suppressed the norepinephrine ($1{\mu}M$) control peak responses with $EC_{50}$ value of 0.08 mM (0.05-0.13, n=5). When tested in Langendorff perfused rabbit heart preparation, the test compound exhibited a negligible inhibitory effect on the rate or force of atrial and ventricular contractions when tested up to 5 mM. The results show smooth muscle-selective relaxant effect of the test compound on intestinal and vascular preparations mediated possibly via blockade of voltage and receptor-operated $Ca^{++}$ channels.

Synthesis and Smooth Muscle-Selective Relaxant Activity of a Piperidine Analogue: 1-(4'-Fluorophenacyl)-4-Hydroxy-4-Phenyl-Piperidinium Chloride

Syed Intasar Hussain Taqvi,Muhammad Nabeel Ghayur,Anwarul Hassan Gilani,Zafar Saeed Saify,Mohammad Tariq Aftab 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.1

The antispasmodic and vasodilator activities of a newly synthesized piperidine derivative (1-(4'- fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride) were studied in vitro. The test compound exhibited a dose-dependent relaxant effect on the spontaneous and K+ (75 mM)- induced contractions of isolated rabbit jejunum with respective EC50 values of 0.01 mM (0.01- 0.02, 95% CI) and 0.30 mM (0.17-0.56). The Ca++ channel blocking (CCB) activity was confirmed when the test compound (0.1-0.2 mM) shifted the Ca++ dose-response curves to the right, similar to that produced by verapamil (0.1-1.0 µM), a standard CCB. In the isolated rabbit aorta, the test compound showed a dose-dependent vasodilator effect on K+ (75 mM)- induced contractions with an EC50 value of 0.08 mM (0.02-0.26) while also suppressed the norepinephrine (1 µM) control peak responses with EC50 value of 0.08 mM (0.05-0.13, n=5). When tested in Langendorff perfused rabbit heart preparation, the test compound exhibited a negligible inhibitory effect on the rate or force of atrial and ventricular contractions when tested up to 5 mM. The results show smooth muscle-selective relaxant effect of the test compound on intestinal and vascular preparations mediated possibly via blockade of voltage and receptoroperated Ca++ channels.