Abdul Jabbar Shah

Blood Pressure Lowering and Vasomodulator Effects of Piperine

This study was aimed to explore underlying mechanism(s) of cardiovascular effects of piperine. Intravenous administration of piperine caused a dose-dependent (1 to 10 mg/kg) decrease in mean arterial pressure (MAP) in normotensive anesthetized rats; the next higher dose (30 mg/kg) did not cause any further change in MAP. The fall in blood pressure (BP) was followed by small increase in MAP after each dose. In Langendorrfs rabbit heart preparation, piperine caused partial inhibition and verapamil caused complete inhibition of force and rate of ventricular contractions and coronary flow. In rabbit aortic rings, piperine inhibited high K+ (80 mM) precontractions and partially inhibited phenylephrine (PE), suggesting Ca2+ channel blockade (CCB), which was further confirmed when pretreatment of tissues with piperine caused rightward shift in Ca2+ concentration-response curves, similar to verapamil. In Ca2+-free medium, piperine (1 to 30 μM) exhibited vasoconstrictor effect. In rat aorta, piperine demonstrated endothelium-independent vasodilator effect and was more potent against high K+ precontractions than PE. In bovine coronary artery preparations, piperine inhibited high K+ precontractions completely. These data indicate that piperine possesses a blood pressure-lowering effect mediated possibly through CCB, while consistent decrease in BP was restricted by associated vasoconstrictor effect. Additionally, species selectivity exists in the CCB effect of piperine.

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.

Chemical composition and mechanisms underlying the spasmolytic and bronchodilatory properties of the essential oil of Nepeta cataria L.

AIM OF THE STUDY The study was aimed to investigate the chemical composition and pharmacological basis for traditional use of essential oil of Nepeta cataria L. (Limiaceae) (Nc.Oil) in gastrointestinal and respiratory disorders. MATERIALS AND METHODS Chemical analysis was carried out through GC-EIMS, 13C NMR and Kovats Retention Indices while pharmacological study was carried out in isolated tissues preparations. RESULTS Four major components; 1,8-cineol (21.00%), alpha-humulene (14.44%), alpha-pinene (10.43%) and geranyl acetate (8.21%) were identified among the 27 compounds in Nc.Oil. In isolated rabbit jejunum, Nc.Oil, papaverine and verapamil inhibited spontaneous and high K+(80 mM) precontractions, as well as shifted the Ca++ concentration-response curves (CRCs) to right, indicating calcium channel blocking activity. In isolated guinea-pig trachea, Nc.Oil and papaverine inhibited carbachol (1 microM) and K+ precontractions with similar potency, while verapamil was more potent against K+. Nc.Oil also potentiated isoprenaline inhibitory CRCs, similar to papaverine, indicating papaverine-like PDE inhibitor activity. In isolated guinea-pig atria, Nc.Oil caused cardiodepression at around 25-80 times higher concentrations, similar to papaverine. CONCLUSIONS These data indicate that Nepeta cataria possesses spasmolytic and myorelaxant activities mediated possibly through dual inhibition of calcium channels and PDE, which may explain its traditional use in colic, diarrhea, cough and asthma.

Bronchodilatory effect of Acorus calamus (Linn.) is mediated through multiple pathways

AIM OF THE STUDY This study was undertaken to provide a pharmacological basis for traditional use of Acorus calamus in airways disorders. MATERIALS AND METHODS Isolated guinea-pig trachea and atria were suspended in organ baths bubbled with carbogen and mechanisms were found using different parameters. RESULTS In isolated guinea-pig tracheal segments, crude extract of Acorus calamus was more effective than carbachol in causing relaxation of high K(+) (80 mM) precontractions, similar to verapamil, suggesting blockade of calcium channels. The n-hexane fraction was equipotent against both precontractions, similar to papaverine, while ethylacetate fraction was more potent against carbachol precontractions but had a negligible dilator effect against K(+), similar to atropine and or rolipram. Pretreatment of tracheal preparations with n-hexane or ethylacetate fractions potentiated isoprenaline-induced inhibitory concentration-response curves, similar to papaverine or rolipram. Pretreatment of tracheal preparations with ethylacetate fraction caused a rightward parallel shift in carbachol response curve at lower concentration (0.003 mg/mL) similar to atropine and a non-parallel shift at higher concentrations (0.01 mg/mL), with reduction of maximum response, similar to rolipram. In isolated guinea-pig atrial preparations, crude extracts, its fractions and papaverine inhibited force and rate of contractions at higher concentrations than the smooth muscle while verapamil was equipotent. CONCLUSION These data indicate the presence of unique combination of airways relaxant constituents in crude extract of Acorus calamus, a papaverine-like dual inhibitor of calcium channels and phosphodiesterase in n-hexane fraction and a novel combination of anticholinergic, rolipram-like phosphodiesterase4 inhibitor in ethylacetate fraction and associated cardiac depressant effect, provide a pharmacological basis for traditional use of Acorus calamus in disorders of airways.

Calcium Channel Blocking Activity of Mentha longifolia L. Explains its Medicinal Use in Diarrhoea and Gut Spasm

Mentha longifolia has a reputation in traditional medicine in the indications of diarrhoea and gut spasm. This study was carried out to provide a possible pharmacological basis for its medicinal use in hyperactive gut disorders. In a castor oil induced diarrhoeal model, the crude extract of Mentha longifolia (Ml.Cr), at doses of 100–1000 mg/kg, provided 31–80% protection, similar to loperamide. In isolated rabbit jejunum preparations, Ml.Cr caused inhibition of spontaneous and high K+‐induced contractions, with respective EC50 values of 1.80 (1.34–2.24; n = 6–8) and 0.60 mg/mL (0.37–0.85; n = 6–8), which suggests spasmolytic activity, mediated possibly through calcium channel blockade (CCB). The CCB activity was further confirmed when pretreatment of the tissue with Ml.Cr (0.3–1 mg/mL) caused a rightward shift in the Ca++ concentration–response curves (CRCs), similar to verapamil. Loperamide also inhibited spontaneous and high K+‐induced contractions and shifted the Ca++ CRCs to the right. Activity‐directed fractionation revealed that the petroleum spirit fraction was more potent than the parent crude extract and aqueous fraction. These data indicate that the antidiarrhoeal and spasmolytic effects of the crude extract of Mentha longifolia are mediated through the presence of CCB‐like constituent(s), concentrated in the petroleum spirit fraction and this study provides indirect evidence for its medicinal use in diarrhoea and spasm. Copyright

Berberis vulgaris Root Bark Extract Prevents Hyperoxaluria Induced Urolithiasis in Rats

Berberis vulgaris is a widely used plant for the treatment of urolithiasis. To evaluate its antiurolithic potential, the crude aqueous‐methanol extract of Berberis vulgaris root bark (Bv.Cr) was tested in an animal model of urolithiasis, developed in male Wistar rats by adding 0.75% ethylene glycol in drinking water. Bv.Cr (50 mg/kg) inhibited CaOx crystal deposition in renal tubules and protected against associated changes including polyuria, weight loss, impaired renal function and the development of oxidative stress in kidneys. Activity‐guided fractionation revealed the concentration of antiurolithic constituent(s) mainly in the aqueous fraction. These data, indicating the presence of antiurolithic activity in Berberis vulgaris root bark, rationalize its medicinal use for the treatment of urolithiasis. Copyright

Antidiarrhoeal and spasmolytic activities of the methanolic crude extract of Alstonia scholaris L. are mediated through calcium channel blockade.

This study was aimed to provide a pharmacological basis to the medicinal use of Alstonia scholaris as an antidiarrhoeal and antispasmodic by using in vivo and in vitro techniques. In the in vivo study the crude extract of Alstonia scholaris (As.Cr), which tested positive for the presence of alkaloids, provided 31–84% protection against castor oil‐induced diarrhoea in mice at 100–1000 mg/kg doses, similar to loperamide. In isolated rabbit jejunum preparation, the As.Cr caused inhibition of spontaneous and high K+ (80 mm)‐induced contractions, with respective EC50 values of 1.04 (0.73–1.48) and 1.02 mg/mL (0.56–1.84; 95% CI), thus showing spasmolytic activity mediated possibly through calcium channel blockade (CCB). The CCB activity was further confirmed when pretreatment of the tissue with the As.Cr (0.3–1 mg/mL) caused a rightward shift in the Ca++ concentration‐response curves similar to verapamil, a standard calcium channel blocker. Loperamide also inhibited spontaneous and high K+ precontractions as well as shifted the Ca++ CRCs to the right. These results indicate that the crude extract of Alstonia scholaris possesses antidiarrhoeal and spasmolytic effects, mediated possibly through the presence of CCB‐like constituent(s) and this study provides a mechanistic base for its medicinal use in diarrhoea and colic. Copyright

Blood Pressure-lowering and Vascular Modulator Effects of Acorus calamus Extract Are Mediated Through Multiple Pathways

This investigation was aimed to provide a pharmacologic basis to the medicinal use of Acorus calamus in cardiovascular disorders. In normotensive anesthetized rats, crude extract of Acorus calamus and its ethylacetate and nHexane fractions caused a fall in mean arterial pressure. In rabbit aorta rings, crude extract was more potent against high K+ (80 mM), ethylacetate against phenylephrine (1 μM), whereas nHexane fraction was equipotent against both precontractions. Crude extract exhibited a vasoconstrictor effect on baseline. Pretreatment of aortic rings with crude extract and its fractions shifted Ca+2 concentration-response curves to the right, similar to verapamil. Crude extract and ethylacetate fraction suppressed phenylephrine peak formation in Ca+2-free medium. In rat aorta preparations, crude extract exhibited endothelium-independent relaxation with a vasodilatory effect against high K+. nHexane fraction caused an endothelium-dependent Nω-nitro-l-arginine methyl ester-sensitive vasorelaxant along with ryanodine-sensitive vasoconstrictor effect on baseline tension and partially inhibited high K+, although ethylacetate fraction caused an endothelium-independent relaxant and endothelium-dependent vasoconstrictor effect. These data indicate that crude extract possesses a combination of effects, relaxant effects mediated possibly through Ca+2 antagonism in addition to a nitric oxide pathway, although the associated vasoconstrictor effects may be meant by nature to offset excessive vasodilatation, thus providing a pharmacologic rationale to its cardiovascular medi-cinal uses.

Studies on the Chemical Composition and Possible Mechanisms Underlying the Antispasmodic and Bronchodilatory Activities of the Essential Oil of Artemisia maritima L.

This study describes the chemical composition of the essential oil of Artemisia maritima (Am.Oil) and the pharmacological basis for its medicinal use in gut and airways disorders. Twenty five compounds, composing 93.7% of the oil, were identified; among these, chrysanthenyl propionate and elixene were identified for the first time from any Artemisia species. The Am.Oil (0.3–1.0 mg/mL) suppressed spontaneous and high K+ (80 mM)-induced contractions in isolated rabbit jejunum, suggestive of an antispasmodic effect mediated possibly through calcium channel blockade. The calcium channel blockade activity was confirmed when pre-treatment of the tissue with Am.Oil (0.01–0.03 mg/mL) shifted the Ca++ concentration-response curves to the right, similar to verapamil and papaverine. In isolated tracheal strips, Am.Oil inhibited carbachol (CCh; 1 μM)-induced contractions more than that induced by K+ and shifted the isoprenaline-induced inhibitory CRCs to the left, similar to papaverine, suggestive of potentiation, while, verapamil was more potent against K+ than CCh-induced contractions and had no potentiating effect on isoprenaline-induced inhibitory CRCs. These data indicate that the Am.Oil exhibited spasmolytic and bronchodilator activities mediated possibly through dual blockade of calcium channels and phosphodiesterase, which provides the pharmacological basis to the medicinal use of Artemisia maritima in colic, diarrhea and possibly asthma.

Antihepatotoxic activity of Saussurea lappa extract on D-galactosamine and lipopolysaccharide-induced hepatitis in mice.

The effects of aqueous‐methanol extract of Saussurea lappa Clarke root (Sl.Cr) was investigated against D‐galactosamine (D‐GalN) and lipopolysaccharide (LPS)‐induced hepatitis in mice. Co‐administration of D‐GalN (700 mg/kg) and LPS (1 μg/kg) significantly raised the plasma transaminase levels (ALT/AST) as compared to the control group (p < 0.05). Pretreatment of mice with different doses of Sl.Cr (150, 300 and 600 mg/kg) significantly prevented the D‐GalN and LPS‐induced rise in plasma levels of ALT and AST in a dose‐dependent manner (p < 0.05). Post‐treatment with Sl.Cr (600 mg/kg) significantly restricted the progression of hepatic damage induced by D‐GalN and LPS (p < 0.05). The improvement in plasma enzyme levels was further verified by histopathology of the liver, which showed improved architecture, absence of parenchyma congestion, decreased cellular swelling and apoptotic cells in treatment groups as compared to the toxin group of animals. These data indicate that the Sl.Cr exhibits hepatoprotective effect in mice and this study rationalize the traditional use of this plant in liver disorders. Copyright