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      Anticholinergic, antihistaminic, and antiserotonergic activity of n-hexane extract of Zanthoxylum alatum seeds on isolated tissue preparations: An ex vivo study

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          Abstract

          Objectives:

          The aim of this study was to evaluate anticholinergic, antihistaminic, and antiserotonergic activity of the n-hexane extract of the seeds of Zanthoxylum alatum (ZAHE) on isolated ileum of rat and guinea pig and fundus of rat.

          Materials and Methods:

          ZAHE was prepared using soxhlet extraction and cumulative concentration response curves were constructed using various doses on the tissues for acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and histamine with or without n-hexane extract. Atropine, ketanserin, and pheniramine maleate were used as antagonists for ACh, serotonin, and histamine, respectively.

          Results:

          ZAHE-induced concentration-dependent inhibition of isolated ileum and fundus in rat and ileum of guinea pig. The half maximal effective concentration (EC 50) of ACh in the presence of atropine (10 −6 M; P < 0.05) and ZAHE (1000 μg/ml; P < 0.01) was significantly higher than EC 50of ACh alone. The EC 50of 5-HT in the presence of ketanserin (10 −5 M; P < 0.01) and ZAHE (1000 μg/ml; P < 0.05) was higher than EC 50of 5-HT alone. Similarly, the EC 50of histamine in the presence of pheniramine maleate (10 −6 M; P < 0.01) and ZAHE (300 μg/ml; P < 0.01 and 1000 μg/ml; P < 0.05) was also significantly higher than EC 50of histamine alone.

          Conclusion:

          From the study, it was observed that ZAHE shows significant anticholinergic, antiserotonergic, and antihistaminic activity. The study provides sufficient evidence that the seeds can be used in gastric disorders, cough, chest infection, etc., as per folklore claims.

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          Most cited references22

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          The enteric nervous system.

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            Studies on the antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities of the Carum copticum seed extract.

            This study describes the antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities of the aqueous-methanolic extract of Carum copticum Benth. seeds (CSE) to rationalize some of its traditional uses. CSE (3-100 mg/kg) caused a dose-dependent fall in arterial blood pressure in anaesthetized rats. In isolated rabbit aorta and jejunum preparations, CSE (0.1-3.0 mg/ml) caused an inhibitory effect on the K+-induced contractions. The calcium channel blocking (CCB) effect was confirmed when CSE shifted the Ca2+ dose-response curves (DRCs) to right similar to verapamil. In isolated guinea-pig tracheal preparations, it caused inhibition of carbachol and K+-induced bronchoconstriction at 0.1-1.0 mg/ml as well as shifted the dose-response curves (DRCs) of carbachol and histamine to the right with suppression of maximum response suggestive of non-specific bronchodilator effect mediated possibly through CCB. Pretreatment of rats with CSE (500 mg/kg orally for 2 days at 12 h intervals) prevented paracetamol (640 mg/kg) and CCl4 (150 ml/kg)-induced rise in serum alkaline phosphatase (ALP) and aminotransferases (AST and ALT). The same dose of CSE was able to prevent the CCl4-induced prolongation in pentobarbital-induced sleeping time in mice confirming its hepatoprotectivity. These results indicate the presence of calcium antagonist(s) in Carum copticum seeds and thus provides sound mechanistic basis for some of their folkloric uses.
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              The abdominal visceral innervation and the emetic reflex: pathways, pharmacology, and plasticity.

              In recent years the role of the area postrema in the emetic reflex has been predominant and the involvement of the abdominal visceral innervation has tended to be overlooked. This paper attempts to redress the balance reflex by reviewing aspects of the existing literature and complementing this with original studies from the ferret. In view of the widespread use of the ferret in studies of emesis and particularly in the characterization of the antiemetic actions of 5-HT3 receptor antagonist, the opportunity is taken to assess the suitability of this species for studies of emesis. It is concluded that the ferret is sensitive to a wide range of emetic stimuli including intragastric irritants, opiate and dopamine receptor agonists, many cytotoxic drugs, and radiation. For several stimuli it is more sensitive than other species and for radiation on the basis of its ED100 it appears to be the most sensitive of the laboratory animals studied. Using electrical stimulation of the central end of the dorsal vagal trunk in the abdomen in conscious and anaesthetized animals, the vagal afferents were shown to be capable of eliciting emesis. Using lesioning studies an involvement of the vagus in the emetic response to a number of cytotoxic drugs (e.g., cisplatinum, cyclophosphamide, mustine) and radiation was demonstrated, although the magnitude of the effect varied with the different stimuli. An attempt is made to reconcile these observations with previous studies of area postrema ablation. The problems of interpreting the effects of nerve lesions are critically discussed in light of preliminary evidence presented here that there may be a degree of plasticity in the emetic pathway following such lesions. The range of antiemetic effects of 5-HT3 receptor antagonists is reviewed and an attempt is made to identify the site(s) at which these agents act. Results are presented that suggest a link between the vagus and 5-HT3 receptor antagonism. These studies are discussed together with others and lead us to propose that (in the ferret) 5-HT3 receptor antagonists have their main antiemetic effect by acting on vagal afferent terminals in the wall of the upper gut with an additional minor site either in the nucleus tractus solitarius or presynaptically on the vagal afferent terminals in the medulla where binding sites for 5-HT3 receptor ligands have recently been demonstrated in this species.
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                Author and article information

                Journal
                Indian J Pharmacol
                Indian J Pharmacol
                IJPharm
                Indian Journal of Pharmacology
                Medknow Publications & Media Pvt Ltd (India )
                0253-7613
                1998-3751
                Jan-Feb 2017
                : 49
                : 1
                : 42-48
                Affiliations
                [1] Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam, India
                Author notes
                Address for correspondence: Dr. Chandana Choudhury Barua, E-mail: chanacin@ 123456gmail.com
                Article
                IJPharm-49-42
                10.4103/0253-7613.201025
                5351237
                28458421
                f1ace0c7-ed03-4212-870d-cf93edb38f6e
                Copyright: © 2017 Indian Journal of Pharmacology

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 06 September 2016
                : 08 December 2016
                Categories
                Research Article

                Pharmacology & Pharmaceutical medicine
                fundus,guinea pig,ileum,ketanserin,wistar rat,zanthoxylum alatum

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