IN VITRO STUDIES ON THE RELAXANT EFFECTS OF THYMOL AND NARINGENIN IN SHEEP AIRWAY SMOOTH MUSCLE
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Date
2011-10
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SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI – 517 502. (A.P) INDIA
Abstract
ABSTRACT:
Thymol is a monoterpenic phenol chiefly found in plants belonging to Lamiaceae family, especially Thymus vulgaris Linn. (Thyme). Naringenin is a flavanone mainly found in citrus fruits (grapes, oranges) and tomato skin. The relaxant effects of these two phytopolyphenols on the airway (tracheal) smooth muscle of sheep subjected to various receptor-and voltage-operated spasmogens like carbachol, histamine, potassium chloride, barium chloride and calcium chloride were investigated in the present study. To elucidate the various mechanisms responsible for relaxant effect, the inhibitory effects of thymol and naringenin on muscarinic receptors, histamine receptors and calcium channels were examined in this study. Also, an attempt was made to study the beta2-
adrenoceptor stimulatory activity of thymol and naringenin with salbutamol, a known beta2-adrenoceptor agonist.
The antimuscarinic and antihistaminergic effects of thymol and naringenin were tested by performing the cumulative concentration-response curves of carbachol and histamine on sheep tracheal strips incubated in the presence of thymol and naringenin at two dose levels of each compound at 1.5 x 10-8M or 15nM and 3 x 10-8M or 30nM and compared with those of atropine, an antimuscarinic agent and cetrizine, an antihistaminic agent at two dose levels of 10-10M or 0.1nM and 10-8M or 10nM each respectively. EC50 for carbachol and histamine in the absence and presence of thymol, naringenin, atropine and cetrizine were calculated and compared. The relaxant effects of thymol and naringenin on carbachol (1.5 x 10-6M) and histamine (1.5 x 10-5M) induced contractions were also studied and their mean IC50 values were calculated. The results showed a clear significant (p < 0.01) rightward shift in the carbachol mean EC50 response in the presence of both the doses of thymol and naringenin comparable to that of atropine. On the other hand, only the higher dose of thymol was able to show a significant (p < 0.01) rightward shift in histamine mean EC50 response comparable to that of cetrizine. This was not evident with both the doses
of naringenin. However, both thymol and naringenin showed appreciable relaxation of carbachol and histamine-induced contractions. The mean IC50 values of thymol and naringenin on histamine induced contractions were comparable with that of salbutamol, a beta2-adrenoceptor agonist although salbutamol seems to be more potent in relaxing sheep tracheal smooth muscle than either thymol or naringenin.
The calcium channel blocking effect of thymol and naringenin were tested by recording the mean IC50 responses of thymol and naringenin on the potassium- (80mM) and barium- (50mM) induced contractions and also by performing the cumulative dose-response curve of calcium chloride on sheep tracheal smooth muscle strips suspended in calcium-free depolarizing Krebs solution containing 0.05mM EGTA. The results showed a clear significant (p < 0.001) leftward shift in the IC50 responses of thymol and naringenin on
tracheal strips precontracted with potassium chloride in the presence of either atropine, cetrizine and nifedipine at 10-6M or 1µ M or in the presence of methylene blue at 3.12 x 10-6M or 3.12 µ M. The IC50 response of naringenin on barium-induced contraction was stronger when compared to that of thymol. The calcium chloride EC50 response was siginficantly (p < 0.001) shifted towards right in the presence of thymol and naringenin at a dose of 3 x 10-8M or 30nM each which was comparable to nifedipine, a calcium channel blocker.
The results in the present study suggest that both thymol and naringenin possess anticholinergic, mild antihistaminergic and calcium channel blocking effects in vitro. However, further in vivo studies using thymol and naringenin are needed to test the utility of these two phytopolyphenols as bronchodilators in actual clinical conditions of respiratory infections.
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