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 © 2010 John Wiley & Sons, Ltd.     

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 © 2009 John Wiley & Sons, Ltd.     

Pharmacological Basis for Medicinal Use of Lens culinaris in Gastrointestinal and Respiratory Disorders

Crude extract of Lens culinaris (Lc.Cr), which tested positive for presence of anthraquinones, flavonoids, saponins, sterol, tannins, and terpenes exhibited protective effect against castor oil‐induced diarrhea in mice at 100–1000 mg/kg. In rabbit jejunum preparations, Lc.Cr caused relaxation of spontaneous contractions at 0.03–5.0 mg/mL. Lc.Cr inhibited carbachol (CCh, 1 μM) and K⁺ (80 mM)‐induced contractions in a pattern similar to dicyclomine, but different from verapamil and atropine. Lc.Cr shifted the Ca⁺⁺ concentration‐response curves to the right, like dicyclomine and verapamil. Pretreatment of tissues with Lc.Cr (0.03–0.1 mg/mL) caused leftward shift of isoprenaline‐induced inhibitory CRCs, similar to papaverine. In guinea‐pig ileum, Lc.Cr produced rightward parallel shift of CCh curves, followed by non‐parallel shift at higher concentration with suppression of maximum response, similar to dicyclomine, but different from verapamil and atropine. Lc.Cr (3.0–30 mg/kg) caused suppression of carbachol (CCh, 100 µg/kg)‐induced increase in inspiratory pressure of anesthetized rats. In guinea‐pig trachea, Lc.Cr relaxed CCh and high K⁺‐induced contractions, shifted CCh curves to right and potentiated isoprenaline response. These results suggest that L. culinaris possesses antidiarrheal, antispasmodic, and bronchodilator activities mediated possibly through a combination of Ca⁺⁺ antagonist, anticholinergic, and phosphodiesterase inhibitory effects, and this study provides sound mechanistic background to its medicinal use in disorders of gut and airways hyperactivity, like diarrhea and asthma. Copyright © 2014 John Wiley & Sons, Ltd.     

Antispasmodic,bronchodilator and blood pressure lowering properties of Hypericum oblongifolium – possible mechanism of action

The crude extract of Hypericum oblongifolium (Ho.Cr), which tested positive for flavonoids, saponins and tannins caused concentration‐dependent (0.1–1.0 mg/mL) relaxation of spontaneous and high K⁺ (80 mM)‐induced contractions in isolated rabbit jejunum preparations, suggesting a Ca⁺⁺ antagonistic effect, which was confirmed when pretreatment of the tissue with Ho.Cr produced a rightward shift in the Ca⁺⁺ concentration‐response curves, like that caused by verapamil. Ho.Cr relaxed carbachol (1 μM) and high K⁺‐induced contractions in guinea pig tracheal preparations. It caused a dose‐dependent (3–100 mg/kg) fall in arterial blood pressure of rats under anesthesia. In isolated guinea pig atria, Ho.Cr caused inhibition of both atrial force and rate of spontaneous contractions. When tested in rabbit aortic rings, Ho.Cr exhibited a vasodilator effect against phenylephrine (1 μM) and high K⁺‐induced contractions. These results indicate that Ho.Cr possesses gastrointestinal, respiratory and cardiovascular inhibitory effects, mediated via a Ca⁺⁺ antagonist mechanism. Copyright © 2009 John Wiley & Sons, Ltd.     

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 © 2009 John Wiley & Sons, Ltd.     

Presence of blood‐pressure lowering and spasmolytic constituents in Buddleja crispa

This aim of this study was to investigate the crude extract of Buddleja crispa (Bc.Cr) and its active constituent(s) for their antihypertensive and antispasmodic activities. The Bc.Cr caused a dose‐dependent (3–10 mg/kg) fall in mean arterial pressure in rats under anesthesia. In rabbit aorta preparations, Bc.Cr (0.03–1 mg/mL) caused inhibition of high K⁺ (80 mM) precontractions. The Bc.Cr (0.03–1 mg/mL) also inhibited spontaneous and high K⁺ precontractions in rabbit jejunum preparations, suggestive of calcium channel blocking (CCB) activity. CCB activity was further confirmed when pretreatment of the tissues with Bc.Cr (0.03–0.10 mg/mL) caused a rightward shift in Ca⁺⁺ concentration response curves, similar to verapamil. Among the pure compounds, BdI‐H3 was more potent against the high K⁺ than spontaneous contractions and was around eight times more potent than Bc.Cr against the spontaneous contractions while the other two compounds, BdI‐2 and BH‐3 were inactive. Activity‐directed fractionation revealed that the hexane fraction was more potent against K⁺ precontractions. These data indicate that Bc.Cr possesses a blood‐pressure lowering effect, mediated possibly through CCB, though additional mechanism(s) cannot be ruled out. Among the pure compounds, Bdl‐H3 is likely to be the active compound involved in the spasmolytic and possibly BP lowering effect of the parent crude extract. Copyright © 2008 John Wiley & Sons, Ltd.     

Antidiarrheal and Antispasmodic Activities of Buddleja polystachya are Mediated Through Dual Inhibition of Ca++ Influx and Phosphodiesterase Enzyme

This study describes the antidiarrheal and antispasmodic activities of the hydro‐alcoholic extract of Buddleja polystachya (Bp.Cr) with possible mode of action explored along with activity‐directed fractionation. Bp.Cr and its aqueous (Bp.Aq) and organic fractions, petroleum ether (Bp.Pet), dichloromethane (Bp.DCM), ethylacetate (Bp.EtAc) and butanol (Bp.But), were tested using the in‐vivo and in‐vitro assays. The crude extract (100–300 mg/kg) showed 20 and 60% protection of castor oil‐induced diarrhea in mice. In isolated rabbit jejunum, Bp.Cr like papaverine inhibited spontaneous and high K⁺ (80 mM)‐induced contractions equi‐potently. In guinea‐pig ileum, Bp.Cr showed a moderate spasmogenic effect. The activity‐directed fractionation revealed that the spasmolytic activity was concentrated in the organic fractions and spasmogenic component in the aqueous fraction. Amongst the organic fractions, BP.DCM and Bp.Pet inhibited spontaneous and high K⁺‐induced contractions equi‐potently, while Bp.But, like verapamil was more potent against high K⁺. The crude extract and its organic fractions caused rightward shift in the Ca⁺⁺‐concentration response curves (CRCs), similar to verapamil, and all except Bp.But potentiated the isoprenaline‐inhibitory CRCs to the left, similar to papaverine. The results of this study indicate that the crude extract of B. polystachya possesses antidiarrheal and antispasmodic activities, mediated possibly through dual inhibition of Ca⁺⁺ influx and phospodiesterase enzyme. Copyright © 2015 John Wiley & Sons, Ltd.     

The Prokinetic,Laxative, and Antidiarrheal Effects of Morus nigra: Possible Muscarinic,Ca2+ Channel Blocking,and Antimuscarinic Mechanisms

Morus nigra Linn. (black mulberry) is used in gastrointestinal ailments. This study demonstrates gut modulatory properties of M. nigra. The prokinetic, laxative, and antidiarrheal activities of M. nigra were assessed in mice, while isolated rabbit jejunum and guinea‐pig ileum were used to explore insight into mechanism(s). At 30 and 70 mg/kg, the crude extract of M. nigra (Mn.Cr) exhibited atropine‐sensitive prokinetic and laxative effects, similar to carbachol (CCh). While at higher doses (100, 300, and 500 mg/kg), Mn.Cr offered protection against castor oil‐induced diarrhea. In rabbit jejunum, Mn.Cr and its chloroform fraction inhibited CCh‐induced contractions more potently compared with high K⁺ (80 mm ). Conversely, petroleum fraction was more potent against high‐K⁺‐induced contractions. At 0.01 mg/mL, Mn.Cr caused a parallel shift in acetylcholine concentration–response curves (CRCs) followed by a non‐parallel shift at 0.03 mg/mL, similar to dicyclomine. At further tested concentrations, Mn.Cr (0.1 and 0.3 mg/mL) and petroleum fraction suppressed Ca²⁺ CRCs, similar to verapamil. In guinea‐pig ileum, Mn.Cr, its aqueous and ethyl acetate fractions exhibited atropine‐sensitive gut stimulant activity along with additional uncharacterized excitatory response in the aqueous fraction only. These results suggest that black mulberry possesses prokinetic, laxative, and antidiarrheal effects, putatively mediated through cholinomimetic, antimuscarinic, and Ca²⁺ antagonist mechanisms, respectively. Copyright © 2016 John Wiley & Sons, Ltd.     

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 N_ω‐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 © 2010 John Wiley & Sons, Ltd.     

Studies on antidiarrheal and antispasmodic activities of Lepidium sativum crude extract in rats

This study was aimed to provide the pharmacological basis for the medicinal use of Lepidium sativum in diarrhea using in vivo and in vitro assays. The seed extract of Lepidium sativum (Ls.Cr) at 100 and 300 mg/kg inhibited castor oil‐induced diarrhea in rats. In isolated rat ileum, Ls.Cr (0.01–5 mg/mL) reversed carbachol (CCh, 1 µ m ) and K⁺ (80 m m )‐induced contractions with higher potency against CCh, similar to dicyclomine. Preincubation of rat ileum with a lower concentration of Ls.Cr (0.03 mg/mL) caused a rightward parallel shift in the concentration–response curves (CRCs) of CCh without suppression of the maximum response, while at the next higher concentration (0.1 mg/mL), it produced a non‐parallel rightward shift with suppression of the maximum response, similar to that of dicyclomine. Ls.Cr shifted the CRCs of Ca⁺⁺ to the right with suppression of the maximum response, similar to verapamil. These data suggest that Lepidium sativum seed extract possesses antidiarrheal and spasmolytic activities mediated possibly through dual blockade of muscarinic receptors and Ca⁺⁺ channels, though additional mechanism(s) cannot be ruled out and this study explains its medicinal use in diarrhea and abdominal cramps. Copyright © 2011 John Wiley & Sons, Ltd.     

Dual Inhibition of Ca+2 Influx and Phosphodiesterase Enzyme Provides Scientific Base for the Medicinal Use of Chrozophora prostrata Dalz. in Respiratory Disorders

The crude ethanolic extract of Chrozophora prostrata (Cp.Cr) was tested using in vivo and ex vivo assays for its possible bronchodilatory effects in order to validate its medicinal use in respiratory disorders, like asthma and cough. Cp.Cr exhibited dose‐dependent inhibition of carbachol (CCh)‐induced bronchospasm in anesthetized rats, similar to aminophylline. When tested on guinea‐pig tracheal preparations, Cp.Cr caused relaxation of both CCh (1 μM) and high K⁺ (80 mM)‐induced contractions with comparable potencies, similar to papaverine, a dual inhibitor of phosphodiesterse (PDE) and Ca⁺² influx. Pre‐treatment of the tracheal tissues with Cp.Cr resulted in potentiation of the inhibitory effect of isoprenaline on CCh‐induced contractions, like that caused by papaverine indicative of PDE inhibitory activity, which was confirmed when Cp.Cr concentration dependently (1 and 3 mg/mL) increased intracellular cAMP levels of the tracheal preparations, like papaverine. Cp.Cr shifted concentrationresponse curves of Ca⁺² constructed in guinea‐pig tracheal preparation towards right with suppression of the maximum response, similar to both verapamil and papaverine. These data indicate bronchodilator activity of Chrozophora prostrata mediated possibly through dual inhibition of PDE and Ca⁺² influx, thus, showing therapeutic potential in asthma with effect enhancing and side‐effect neutralizing potential Copyright © 2016 John Wiley & Sons, Ltd.     

Species Differences in the Antidiarrheal and Antispasmodic Activities of Lepidium sativum and Insight into Underlying Mechanisms

The aim of this study was to see if the crude extract of Lepidium sativum (Ls.Cr) exhibits species specificity in its antidiarrheal and antispasmodic activities along with insight into the underlying mechanisms using the in‐vivo and in‐vitro experiments. Ls.Cr inhibited castor oil‐induced diarrhea in mice at doses (300 and 1000 mg/kg) three times higher dose than for rats. In isolated rat ileum and jejunum, Ls.Cr completely inhibited carbachol (CCh), low K⁺ (25 mM) and high K⁺ (80 mM)‐induced contractions, while in guinea‐pig tissues, Ls.Cr caused complete inhibition of only CCh‐induced contraction. In rabbit tissues, Ls.Cr completely inhibited CCh and low K⁺‐induced contractions sensitive to K⁺ channel antagonists. Pretreatment of guinea‐pig and rat tissues with Ls.Cr caused a rightward shift in CCh‐induced contractions in a pattern similar to dicyclomine, while in rabbit and rat tissues, Ls.Cr shifted isoprenaline curves to the left similar to papaverine. These data indicate that the antidiarrheal and antispasmodic activities of L. sativum are species dependent, mediating its antispasmodic effect through combinations of multiple pathways including activation of K⁺ channels, and inhibition of muscarinic receptors, Ca⁺⁺ channels and PDE enzyme. Rat tissues showed the highest potency. Based on the results, we recommend using multiple species to know the real pharmacological profile of medicinal products. Copyright © 2012 John Wiley & Sons, Ltd.     

Ca++ channel blocking activity of Artemisia scoparia extract

Intravenous administration of a hydro-methanolic extract of Artemisia scoparia (3–30 mg/kg) produced hypotensive and bradycardiac effects. These effects remained unaltered in atropine treated animals and the presence of the extract did not modify the vasoconstrictor response of norepinephrine, indicating that cardiovascular effects of the plant extract are not mediated through activation of muscarinic receptors or adrenoceptor blockade. In the in vitro studies, it suppressed the spontaneous movements of rabbit jejunum in a concentration-dependent (0.1-1 mg/mL) manner. The plant extract inhibited K⁺-induced tonic contraction in a manner similar to that of verapamil. Exposure of tissue to Ca⁺⁺-free Kreb's solution abolished the spontaneous movements which were restored on addition of Ca⁺⁺. In tissue pretreated with plant extract or verapamil, addition of Ca⁺⁺ (50 μM) failed to restore spontaneous contractions. These data indicate that Artemisia scoparia cntains Ca⁺⁺ channel blocker-like constituent(s) which may explain the hypotensive effect observed in vivo and the traditional use of the plant as a spasmolytic.     

Bronchodilator Activity of Aerial Parts of Polygonatum verticillatum Augmented by Anti‐inflammatory Activity: Attenuation of Ca2+ Channels and Lipoxygenase

Polygonatum verticillatum is commonly used for the treatment of asthma and inflammation. The current study was aimed to scrutinize the pharmacological profile of methanolic extract of the aerial parts (PA). Isolated tracheal preparations were used for the evaluation of bronchodilatory activity, whilst the in vivo carrageenan‐induced paw oedema test and an in vitro lipoxygenase (LOX) inhibitory assay were used for the assessment of the anti‐inflammatory profile of PA. When tested against carbachol and K⁺ (80 mM)‐induced contractions, PA caused complete inhibition of isolated rabbit tracheal preparations in a dose‐dependent mode, similar to verapamil. While elucidating possible mechanism, PA shifted the Ca²⁺ concentration–response curves to the right, analogous to that produced by verapamil, confirming a Ca²⁺ channel blocker‐like activity. PA provoked profound reduction in paw oedema with a maximum protection of 60.87% at 200 mg/kg i.p. in a dose‐dependent manner which was augmented by its prominent LOX inhibitory activity (IC₅₀: 125 µg/mL). These findings authenticated its therapeutic potential in the treatment of asthmatic and inflammatory conditions. Copyright © 2012 John Wiley & Sons, Ltd.     

Calcium Channel Blocking Activity in Desmostachya bipinnata (L.) Explains its use in Gut and Airways Disorders

Desmostachya bipinnata, despite of its popular medicinal uses, has not been widely studied for its effect in diarrhea, indigestion, and asthma. The aim of the present investigation was to provide scientific rationale for these applications. The crude aqueous‐methanolic extract of D. bipinnata (Db.Cr) was evaluated through in vivo and in vitro experiments. Db.Cr (100–500 mg/kg) protected mice against castor oil–induced diarrhea, similar to loperamide. When tested on gut preparations, Db.Cr produced an atropine‐sensitive spasmogenic effect in rabbit jejunum up to 5 mg/mL, followed by a partial relaxation at 10 mg/mL. With atropine preincubation, a verapamil‐like inhibitory effect was evident against spontaneous and high K⁺ (80 mM)–induced contractions. The maximum stimulant effect was comparable with the acetylcholine‐induced maximum contraction and was similarly reproducible in guinea pig ileum. Db.Cr inhibited carbachol (1 μM)‐induced contraction in rabbit trachea but caused an atropine‐sensitive accentuation of high K⁺–induced contraction at 0.003–0.3 mg/mL followed by inhibition at 1–5 mg/mL. On activity‐directed fractionation, inhibitory effect was concentrated on organic and stimulant effect in aqueous fraction. This study, suggesting the presence of calcium antagonist activity, possibly underlying its medicinal effect in hyperactive gut and respiratory disorders, and cholinergic activity, possibly underlying its digestive effect, provides rationale for these therapeutic uses of D. bipinnata. Copyright © 2012 John Wiley & Sons, Ltd.     

Effects of the essential oil of Croton zehntneri,and its constituent estragole on intestinal smooth muscle

The effects on isolated guinea-pig ileum of the essential oil of Croton zehntneri (CZEO) and of its main constituent estragole (57% of CZEO by weight) were studied. CZEO and estragole (0.1–100 μg/mL) decreased the tonus in 56% and 61.5%, respectively, of the muscles. At concentrations above 10 μg/mL, they induced spontaneous rhythmic movements of small amplitude (less than 11% of the potassium contraction peak to peak). At concentrations from 1 to 100 μg/mL and with similar potencies, these agents blocked the contractions induced by acetylcholine, histamine and 50 mM K⁺ and caused relaxation of already established potassium contractures. Tested separately, CZEO, estragole and anethole (28% of CZEO by weight) blocked the contraction induced by Ca⁺⁺ in the presence of 50 mM K⁺, but CZEO was more potent than estragole or anethole in blocking the Ca⁺⁺-induced contractions than those induced by K⁺. With large increases in the agonist concentration, the action of the oils on the contractions induced by Ca⁺⁺ was reversible; however, their effect on contractions induced by histamine or ACh was not. The data show that the essential oil of Croton zehntneri has an effect on intestinal smooth muscle that is predominantly antispasmodic, and attributable in part to the effect of estragole, a major constituent. © 1997 John Wiley & Sons, Ltd.     

Spasmolytic actions of warifteine,a bisbenzylisoquinoline alkaloid isolated from the root bark of Cissampelos sympodialis Eichl. (menispermaceae)

Warifteine, a bisbenzylisoquinoline alkaloid isolated from the root bark of Cissampelos sympodialis Eichl., produced a reversible, nonspecific and noncompetitive antagonism of histamine, carbachol and bradykinin induced contractions of the guinea-pig ileum. The corresponding pD'₂ values (mean±SE) were 4.90±0.15, 4.95±0.20 and 5.03±0.11. Warifteine also antagonized oxytocin and bradykinin induced contractions of the rat uterus in a similar manner with pD'₂ values of 4.30±0.26 and 3.76±0.06 respectively. In the guinea-pig trachea, the alkaloid inhibited spontaneous tone (IC₅₀, 1.1 × 10^?5M) as well as carbachol induced sustained contractions (IC₅₀, 2.9 × 10^?5M). As warifteine antagonized KCI induced contractions of the guinea-pig ileum (pD'₂ value 4.57±0.10), inhibition of Ca⁺⁺ influx through voltage operated Ca⁺⁺ channels may be partially responsible for its antispasmodic activity. However, the reported local anaesthetic property of warifteine may not contribute to the observed muscle relaxation as procaine failed to reduce the spontaneous tone or consistently antagonize carbachol induced contractions of the trachea and was inactive in inhibiting voltage operated Ca⁺⁺ channels in the ileum.     

Anti‐platelet Activity of Erythro‐(7S,8R)‐7‐acetoxy‐3,4,3′,5′‐tetramethoxy‐8‐O‐4′‐neolignan from Myristica fragrans

Platelets play a critical role in pathogenesis of cardiovascular disorders and strokes. The inhibition of platelet function is beneficial for the treatment and prevention of these diseases. In this study, we investigated the anti‐platelet activity of erythro‐(7S,8R)‐7‐acetoxy‐3,4,3′,5′‐tetramethoxy‐8‐O‐4′‐neolignan (EATN), a neolignan isolated from Myristica fragrans, using human platelets. EATN preferentially inhibited thrombin‐ and platelet‐activating factor (PAF)‐induced platelet aggregation without affecting platelet damage in a concentration‐dependent manner with IC₅₀ values of 3.2 ± 0.4 and 3.4 ± 0.3 μM, respectively. However, much higher concentrations of EATN were required to inhibit platelet aggregation induced by arachidonic acid. EATN also inhibited thrombin‐induced serotonin and ATP release, and thromboxane B₂ formation in human platelets. Moreover, EATN caused an increase in cyclic AMP (cAMP) levels and attenuated intracellular Ca²⁺ mobilization in thrombin‐activated human platelets. Therefore, we conclude that the inhibitory mechanism of EATN on platelet aggregation may increase cAMP levels and subsequently inhibit intracellular Ca²⁺ mobilization by interfering with a common signaling pathway rather than by directly inhibiting the binding of thrombin or PAF to their receptors. This is the first report of the anti‐platelet activity of EATN isolated from M. fragrans. Copyright © 2013 John Wiley & Sons, Ltd.     

Bisnordihydrotoxiferine and vellosimine from Strychnos divaricans root: Spasmolytic properties of bisnordihydrotoxiferine

Bisnordihydrotoxiferine and vellosimine, two tertiary indole alkaloids have been isolated from the root of Strychnos divaricans. Bisnordihydrotoxiferine antagonized in a nonspecific manner, oxytocin and acetylcholine induced contractions in the rat uterus and acetylcholine and histamine responses in the guinea-pig ileum. Bisnordihydrotoxiferine, like verapamil, produced effects on voltage dependent Ca²⁺ channels. For example in guinea-pig ileum, bisnordihydrotoxiferine (pD'₂ 3.92±0.09) and verapamil (pD'₂ 6.00±0.11) inhibited KCl induced contractions. Furthermore, bisnordihydrotoxiferine (pD'₂ 4.37±0.02) and verapamil (pD'₂ 6.83±0.10) also antagonized CaCl₂ induced contractions of K⁺-depolarized rat uterus. When compared with sodium nitroprusside, an antagonist of receptor operated Ca²⁺ channels, bisnordihydrotoxiferine had no effect. However, in the aorta, the alkaloid (IC₅₀, 6.10 × 10^?6M) antagonized the intracellular calcium dependent transient contractions of noradrenaline and it was about four times more potent than procaine (IC₅₀, 2.30 × 10^?5M), a known inhibitor of the release of Ca²⁺ from intracellular stores. Bisnordihydrotoxiferine may produce nonspecific spasmolytic actions mainly by inhibiting intracellular calcium mobilization and to a lesser extent by inhibiting voltage dependent calcium channels in smooth muscles.     

The calcium channel blocking and phosphodiesterase inhibitory activities of the extract of Andropogon muricatus explains its medicinal use in airways disorders

The present work was carried out to provide a pharmacological base for the medicinal use of Andropogon muricatus in airways disorders, such as asthma. In isolated guinea‐pig tracheal strips, the crude extract of Andropogon muricatus exhibited a non‐specific relaxant effect against carbachol (1 µ m ) and high K⁺ precontractions, with EC₅₀ values of 0.10 (0.07–0.11) and 0.15 mg/mL (0.11–0.18), respectively, similar to papaverine, while verapamil was more potent against high K⁺. This suggests the involvement of a non‐specific relaxant effect, mediated possibly through Ca⁺⁺ channel blockade and phosphodiesterase inhibition. The functional nature of the relaxant effect was further confirmed through indirect evidence when pretreatment of the tissues with the plant extract caused potentiation of the isoprenaline inhibitory response curves, similar to papaverine, while the effect of verapamil remained unchanged. These data indicate that the crude extract of Andropogon muricatus contains constituent(s) that mediate the tracheal relaxant effect, possibly through dual inhibition of Ca⁺⁺ channels and phosphodiesterase and provide pharmacological evidence for its medicinal use in airways disorders, particularly asthma. Copyright © 2011 John Wiley & Sons, Ltd.