Potential antiasthmatic, antihistaminic and antidiarrhoeal effects of cryptolepine, the major alkaloid of cryptolepis sanguinolenta (lindl.) schltr (periplocaceae), in experimental animals.

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August, 2015
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Cryptolepine (CLP) is a known antimuscarinic at M1, M2 and M3 receptors. Antimuscarinics tend to find use in asthma due to their bronchodilatory effect. Coupled with this, is its established anti-inflammatory effect. As asthma medications are either bronchodilative or anti -inflammatory agents, the effect of CLP was studied in certain animal models of asthma. In addition some asthma patients tend to present with certain conditions such as diarrhoea due to release of certain mediators like histamine and general vagal stimulation. In that vein, the antidiarrhoeal effect of cryptolepine was also evaluated. Ovalbumin-induced airway guinea pig model was used in the study to evaluate airway inflammation. Allergic inflammatory response was also evaluated using skin prick test. Results revealed that CLP at a dose range of 10-100 mg/kg significantly and dose dependently inhibited inflammatory cells in the periphery. These effects corresponded with the histopathology in the airways. Also evident in the histopathology is protection of CLP against airway inflammation and remodeling viewed in parameters such as thickening of basement membrane and epithelial cells, smooth muscle hypertrophy and hyperplasia in goblet cells. There was significant reduction in the oedema at various doses of CLP compared to the control in the skin prick test, the effect still greater after 24 hours suggesting that it might have an effect in both early and late phase of inflammation. Cryptolepine showed dose-dependent protection in histamine-induced bronchoconstriction from a dose of 10- 100 mg /kg which was significant even after 24 hrs. At doses of 10, 30 and 100 mg/kg of CLP there was graded decrease mucus secretion in the tracheal phenol red model. These effects could also be attributed to stablilizing mast cells apart from its known antimuscarinic and antihistaminic effect. This is evident in the protection showed by cryptolepine at a dose of 30 and 100 µg/ml in compound 48/80 induced rat mesentery mast cell degranulation. CLP (10, 30 and 100 mg/kg) reduced diarrhoea in the castor oil induced diarrhoea model from 100% in control group to 46.5-78.89%. This effect could be partly due to inhibition of peristalsis of GIT by cryptolepine, evidenced by inhibition of transition of charcoal meal from 100% in control group to 17.7% and 37.07%in the charcoal meal test. CLP therefore demonstrated antiasthmatic, antidiarrhoeal and antihistaminic in animal models.
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A thesis submitted in fulfillment of the requirements for the degree of Master of Philosophy Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, 2015
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