Carum copticum L.: A Herbal Medicine with Various Pharmacological Effects - Respiratory effects
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Biomed Res Int. 2014; 2014: 569087. Published online 2014 Jun 25. doi: 10.1155/2014/569087
PMCID: PMC4096002 PMID: 25089273
Carum copticum L.: A Herbal Medicine with Various Pharmacological Effects
Mohammad Hossein Boskabady, 1 ,* Saeed Alitaneh, 2 and Azam Alavinezhad 1
Carum copticum L. commonly known as “Ajwain” is cultivated in many regions of the world including Iran and India, states of Gujarat and Rajasthan. Traditionally, C. copticum has been used in the past for various therapeutic effects including bloating, fatigue, diarrhea, abdominal tumors, abdominal pain, respiratory distress, and loss of appetite. It has other health benefits such as antifungal, antioxidant, antibacterial, antiparasitic, and hypolipidemic effects. This plant contains different important components such as carbohydrates, glucosides, saponins and phenolic compounds (carvacrol), volatile oils (thymol), terpiene, paracymene and beta-pinene, protein, fat, fiber, and minerals including calcium, phosphorus, iron, and nicotinic acid (niacin). In the previous studies, several pharmacological effects were shown for C. copticum. Therefore, in this paper, the pharmacological effects of the plant were reviewed..................
5.1. Respiratory Effects
One of the therapeutic effects of C. copticum is its effect on respiratory system. This plant is used as antiasthma and antidyspnea in traditional medicine. In this context, multiple studies have been carried out including relaxant and inhibitory effects on histamine receptors, stimulatory effect on adrenoreceptors of guinea pigs' tracheal smooth muscles, antitussive effect in guinea pigs, and its bronchodilatory effect on airways of asthmatic patients.
C. copticum showed potent relaxant effect on tracheal smooth muscles which was not due to its content of thymol or competitive antagonistic effect on cholinergic receptors. The existence of α-pinene in essential oil of this plant showed anticholinergic activity (functional antagonism) . Relaxant effects of different fractions from C. copticum including fractions 1, 2, 3, and 4 in guinea pigs' tracheal smooth muscle were shown. For preparation of four fractions, the essential oil was freezed at 0°C overnight. The white crystals were collected by filtration, air dried, and subjected to NMR analysis. The filtrate (1 mL) was chromatographed on a silica gel (70–230 mesh). The column was eluted with solvent mixtures comprising petroleum ether (40–60°C) and chloroform with varying concentrations. Fractions (25 mL) were collected and analogous fractions according to their TLC profile were mixed (solvent system comprising petroleum ether 40–60°C): chloroform (4 : 1) and the spots were visualized using sulfuric acid (50%, v/v). The relaxant effect of fraction 2 of the plant (suggested to be carvacrol) was comparable to the effect of theophylline and more potent than other fractions. Fraction 3 also showed a relaxant effect on tracheal smooth muscle to lesser extent. In addition the results showed that the relaxant effect of fractions 2 and 3 was not due to their inhibitory effect on muscarinic or stimulatory property on beta-adrenergic receptors .
Inhibitory effect of C. copticum on histamine (H1) receptors of isolated guinea pig tracheal smooth muscle showed a competitive antagonistic effect of the plant on H1 receptors; however, its effect was lower than chlorpheniramine .
Stimulatory effect of essential oil, aqueous, and ethanolic extract of C. copticum on beta 2 adrenoceptors was examined in isolated guinea pigs tracheal chain. The results showed a stimulatory effect only for ethanolic extract of C. copticum on beta 2 adrenoceptors . A xanthine-like activity was also shown for the extract of C. copticum .
In the study of Gilani et al. bronchodilator effect of C. copticum seed extract in presence of high K+ (50 mM) and carbachol on guinea pig tracheal preparation was evaluated. Results demonstrated that C. copticum made dose-dependent relaxation (dose 0.1–1 mg/mL) with a possible mechanism of calcium channel blocking effect .
The antitussive effects of aerosols of two different concentrations of aqueous and macerated extracts, carvacrol, codeine, and saline were examined by enumerating the number of coughs due to citric acid aerosol 10 min after exposing animals to aerosols of different solutions. Results showed that antitussive effects of aqueous and macerated extracts were similar to codeine which is possibly due to its bronchodilator properties. Nevertheless, carvacrol, one constituent of C. copticum with potent bronchodilatory effect, did not show any antitussive effect which suggested different afferent neural route between cough and bronchoconstriction .
Bronchodilatory effect of oral administration of boiled extract from C. copticum and theophylline in asthmatic patients was also examined. Different pulmonary function tests (FEV1, PEF MMEF, MEF75, MEF50, MEF25, and sGaw) were measured 15 min after administration of different drugs and continued until 180 min after drug administration. The results showed that C. copticum has a relatively bronchodilatory effect on asthmatic airways which was comparable with the effect of theophylline at concentrations used . The results of this study suggest that this plant could be of therapeutic value as a bronchodilatory drug in patients with obstructive airway diseases.
One of the main components of C. copticum is thymol. The effect of thymol on tracheal and ileum smooth muscles and ciliary motion of respiratory system in rat showed that thymol has a dose-dependent antispasmodic property and increases mucosa transfer due to ciliary motion . Additionally, the antispasmodic effect of thyme extract was demonstrated which is suggested to be due to phenolic volatile oil compounds such as thymol .
The relaxant effect of carvacrol, one of the main constituents of C. copticum, on tracheal smooth muscle of guinea pigs has been shown which was greater than the effect of theophylline .
Other plants containing carvacrol such as Carum carvi  also showed relaxant effects on tracheal smooth muscle. Fraction 2 of C. copticum, which is suggested to be carvacrol, also revealed relaxant effect on tracheal smooth muscle . Therefore, the main constituent of C. copticum, carvacrol, may have relaxant effects on the tracheal smooth muscle.
To examine the possible mechanism(s) responsible for the relaxant effect of carvacrol on tracheal smooth muscle, its effect on histamine receptors was evaluated in tracheal smooth muscle of guinea pigs by measuring EC50 histamine (effective concentration of histamine causing 50% of maximum response) in the presence of carvacrol and chlorpheniramine. The results of this study showed a competitive antagonistic effect of carvacrol at histamine H1 receptors. In addition, the results suggested its stimulatory effect on β-adrenergic receptors and also a blocking effect at muscarinic receptors  for carvacrol. In fact, stimulatory effect of carvacrol on β2-adrenoceptors was proved by performing isoprenaline concentration response curve and measurement of EC50 in the presence of the carvacrol, propranolol, and saline on tracheal smooth muscle of guinea pigs in nonincubated and incubated with chlorpheniramine (to block histamine H1 receptors) conditions. The results showed parallel leftward shift of isoprenaline concentration response curve and lower EC50 in the presence of carvacrol and higher EC50 in the presence of propranolol compared to the results of saline . These results showed a clear β2-adrenoceptors stimulatory effect for carvacrol. In addition, the inhibitory effect of carvacrol on muscarinic receptors which is the other possible mechanism for its relaxant effect on the tracheal smooth muscle was also studied. The rightward shift in methacholine-response curves and the increased EC50 in the presence of different concentrations of carvacrol compared with saline were seen which showed possible competitive antagonistic effects of carvacrol at muscarinic receptors . These results suggest that the mechanism of relaxant effect of carvacrol similar to plant extract could have inhibitory effects on muscarinic and histamine receptors and stimulatory effect on β2-adrenoceptors or combinations of the three mechanisms.
However, carvacrol with a potent relaxant effect on tracheal smooth muscle shows no antitussive effect .
With regard to the lung inflammation in different respiratory diseases, mainly asthma, the anti-inflammatory and immunomodulatory effects of carvacrol were also examined in several studies. The effect of carvacrol on cell culture supernatants of macrophages in porcine induced alveolar inflammatory showed inhibitory effect of carvacrol on TNF-α, IL-1β, and TGF-β . Carvacrol also inhibited secretion of TNF-α and IL-1β in porcine alveolar macrophage . Anti-inflammatory effect of carvacrol was also evaluated by measurement of exudates volume and leukocyte migration in plural cavity due to carrageenan injection to this cavity which showed a preventive effect of carvacrol on exudates volume and leukocyte migration (in vivo and in vitro) and suggested an inhibitory effect on COX-1 and COX-2 and 5-lipoxygenase . In addition carvacrol also depicted a preventive effect on serum levels of endothelin, total protein, histamine, NO, and total white blood cells, differential white blood cells (WBC) count and tracheal responsiveness in ovalbumin sensitized guinea pigs [38, 39]. Table 2 summarizes respiratory effects of C. copticum and its constituents thymol and carvacrol.
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