Ginger facilitates cholinergic activity possibly due to blockade of muscarinic autoreceptors in rat stomach fundus

Ginger (Zingiber officinale) is a universally known food plant reputed for its medicinal use in gastrointestinal disorders as a prokinetic and laxative. We recently showed that 70% aqueous-methanolic extract of ginger (Zo.Cr) exhibits prokinetic activity in rats via activation of post-synaptic muscarinic M3 receptor in rat stomach fundus. In view of the physiological significance of pre-synaptic muscarinic M1 and M2 autoreceptors, this study was undertaken to further look into the possible mode of action of the prokinetic effect of ginger through inhibition of pre-synaptic muscarinic receptors. Isolated tissue bath experiments were performed with Sprague-Dawley rat stomach fundus strip preparations immersed in Kreb\u27s solution at 37 degrees C. Carbachol (CCh) maximum responses (1 microM) were obtained in rat stomach fundus. Zo.Cr, given in multiple increasing bolus concentrations (0.01-0.1 mg/ml) 10 min prior to administration of CCh, potentiated the CCh peak responses showing that it is possibly inhibiting the pre-synaptic muscarinic receptors. Like wise, increasing bolus concentrations of pirenzepine (0.03-0.3 microM) and himbacine (0.01-0.03 microM), standard muscarinic M1 and M2 antagonists respectively, also potentiated the CCh responses. These results show that ginger, in addition to having a direct cholinergic agonistic effect on the post-synaptic M3 receptors, also has a possible inhibitory effect on pre-synaptic muscarinic autoreceptors, similar to standard muscarinic antagonists, thus reiterating the gastric stimulant effect of this age-old plant

Antihypertensive, antidyslipidemic and endothelial modulating activities of Orchis mascula

The objective of this study was to investigate the possible mode(s) of action for the medicinal use of Orchis mascula (OM) (family Orchidaceae) in hypertension and dyslipidemia. In spontaneously hypertensive rats (SHRs), OM significantly (

Studies on two polyherbal formulations (ZPTO and ZTO) for comparison of their antidyslipidemic, antihypertensive and endothelial modulating activities

Background Cardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs. Methods To assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and O: Orchis mascula, different animal models including, tyloxapol and high fat diet-induced dyslipidemia and spontaneously hypertensive rats (SHR) were used. Effect on endothelial function was studied using isolated tissue bath set up coupled with PowerLab data acquisition system. The antioxidant activity was carried out using DPPH radical-scavenging assay. Results Based on preliminary screening of the ingredients of POL-10 in tyloxapol-induced hyperlipidemic rats, ZPTO and ZTO containing four active ingredients namely; Z, P, T and O were identified for further studies and comparison. In tyloxapol-induced hyperlipidemic rats, both ZPTO and ZTO caused significant reduction in serum triglyceride (TG) and total cholesterol (TC). In high fat diet-fed rats, ZPTO decreased TC, low-density lipoproteins cholesterol (LDL-C) and atherogenic index (AI). ZTO also showed similar effects to those of ZPTO with additional merits being more effective in reducing AI, body weight and more importantly raising high-density lipoproteins. In SHR, both formulations markedly reduced systolic blood pressure, AI and TG levels, ZTO being more potent in reversing endothelial dysfunction while was devoid of cardiac stimulatory effect. In addition, ZTO also reduced LDL-C and improved glucose levels in SHR. In DPPH radical-scavenging activity test, ZTO was also more potent than ZPTO. Conclusion The modified formulation, ZTO was not only found more effective in correcting cardiovascular abnormalities than ZPTO or POL-10 but also it was free from tachycardiac side-effect, which might be observed because of the presence of Piper nigrum in ZPTO

Gut modulatory effects of Daphne oleoides are mediated through cholinergic and Ca++ antagonist mechanisms.

Context: The present study describes the spasmogenic and spasmolytic activities of Daphne oleoides Schreb. (Thymelaeaceae), exploring the possible underlying pharmacological mechanisms. Aim: Pharmacological investigation of Daphne oleoides to provide evidence for its therapeutic application in gastrointestinal motility disorders. Materials And Methods: Methanol crude extract of Daphne oleoides (Do.Cr) was studied in gastrointestinal isolated tissues. Results: In spontaneously contracting rabbit jejunum preparations, Do.Cr at 0.3-3.0 mg/mL caused moderate stimulation, followed by relaxant effect at the next higher concentrations (5.0-10mg/mL). In presence of atropine, spasmogenic effect was blocked and the relaxation was emerged, suggesting that the spasmogenic effect of Daphne oleoides is mediated through activation of muscarinic receptors. When tested against the high K+ (80mM)-induced contractions, Do.Cr (0.3-5.0mg/mL), like verapamil, inhibited the induced contractions, suggesting Ca++ channel blockade (CCB) effect. The CCB effect was further confirmed when pre-treatment of the tissue with Do.Cr shifted the Ca++ concentration-response curves to the right, similar to that caused by verapamil. DISCUSSION and Conclusion: These results indicate that Daphne oleoides exhibits gut excitatory and inhibitory effects, occurred via cholinergic and Ca++ antagonistic pathways, respectively

Gut modulatory and antiplatelet activities of Viscum cruciatum

Viscum cruciatum Sieber (Viscaceae) is widely used in folk medicine for various gastrointestinal and inflammatory disorders. The crude extract of Viscum cruciatum (VCr), which tested positive for alkaloids, flavonoids, coumarins, saponins, sterols, tannins, and terpenes, caused concentration-dependent (0.01–3.0 mg/mL) relaxation of spontaneous and K+ (80 mM)-induced contractions of isolated rabbit jejunum, similar to that caused by verapamil. VCr shifted the Ca2+ concentration–response curves to the right with suppression of the maximum response, like verapamil. In guinea-pig ileum preparations, VCr caused atropine-sensitive spasmogenic effects. When tested for its effect on human platelets, VCr inhibited the adrenaline and adenosine 5′-diphosphate (ADP)-induced human platelet aggregation at the concentration range of 0.3–1.2 mg/mL. These observations indicate the presence of spasmogenic, spasmolytic, and antiplatelet activities in Viscum cruciatum mediated through cholinergic and calcium channel antagonist activities along with the blockade of adrenergic and ADP receptors, respectively, which explains its medicinal use in gut motility and inflammatory disorders

Antispasmodic, bronchodilator and vasodilator activities of (+)-catechin, a naturally occurring flavonoid

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 right-ward 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 microM) and K(+)-induced contractions in a similar fashion. In PE-contracted, endothelium-intact aorta, this vasodilator effect was partially blocked by Nomega-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