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Relaxant effects of different fractions of essential oil from Carum copticum on guinea pig tracheal chains.

In previous studies, the relaxant and anticholinergic (functional antagonism), histamine(H1) inhibitory, and xanthine-like activity effect of Carum copticum have been demonstrated on guinea pig tracheal chains. To investigate the effective component(s) of this plant, responsible for the observed bronchodilatory effect, fractionation of the essential oil from Carum copticum was carried out and the relaxant effects of different fractions were examined in this study. The bronchodilatory effect of different fractions of essential oil from Carum copticum and theophylline in comparison with ethanol was examined by their relaxant effects on precontracted tracheal chains of guinea pig by 60 mM KCl (group 1) and 10 microM methacholine in two different conditions including: non-incubated tissues (group 2) and incubated tissues with 1 microM propranolol and 1 microM chlorpheniramine (group 3). In addition the relaxant effect of carvacrol was also examined on precontracted tracheal chains of guinea pig by 10 microM methacholine (group 4), (for each group, n = 5). In group 1 experiments, only theophylline and fraction 2 showed significant relaxant effect compared to that of ethanol. Fraction 2 and 3 of essential oil from carum copticum showed potent and volume (concentration) dependent relaxant effects comparable to that of theophylline in groups 2 and 3 experiments. The relaxant effects of different volumes of these two fractions were significantly higher than that of ethanol (p < 0.05 to p < 0.002 ). The volumes of fraction 1 showed relatively small relaxant effects in groups 2 and 3 experiments which were not significantly different from that of ethanol. However, the relaxant effect of different volumes of fractions 2 and 3 obtained in group 2 experiments were not significantly different from those of group 3 experiments. The volumes of fraction 4 did not show any relaxant effects. In addition volumes of carvacrol also showed comparable relaxant effect with those of fraction 2 and theophylline which was significantly greater than that of ethanol. These results indicate that the relaxant effect of essential oil from carum copticum is mainly due to its fraction 2 which is presumably carvacrol and to lesser extent due to fraction 3, and their relaxant effects are not due to anticholinergic or beta-adrenegic stimulatory effects.

Animals↗

Antitussive effect of Carum copticum in guinea pigs.

Several therapeutic effects including anti-asthma and dyspnea have been described for the seeds of Carum copticum In previous studies the relaxant and anticholinergic (functional antagonism) effects, histamine (H(1)) inhibitory effect of Carum copticum have been demonstrated on guinea pig tracheal chains. In the present study the antitussive effect of this plant was evaluated. The antitussive effects of aerosols of two different concentrations of aqueous and macerated extracts and carvacrol, codeine, and saline were tested by counting the number of coughs produced due to aerosol of citric acid 10 min after exposing animals to aerosols of different solutions (for carvacrol n=5 and for other solutions n=6). The results showed significant reduction of cough number obtained in the presence of both concentrations of aqueous and macerated extracts and codeine (p<0.001 for extracts and p<0.01 for codeine). The cough number obtained in the presence of higher concentration of aqueous and macerated extracts was significantly less than those of lower concentrations (p<0.05 for both extracts). In addition the cough number obtained in the presence of both concentrations of aqueous and macerated extracts was significantly lower than that of codeine (p<0.05 to 0.001). However, carvacrol did not show any antitussive effect. These results indicated an antitussive effect of Carum copticum which was even greater than that of codeine at concentrations used. In addition the antitussive effect of Carum copticum was not due to its main constituent, carvacrol.

Animals↗

Diuretic activity of the aqueous extracts of Carum carvi and Tanacetum vulgare in normal rats.

In the Moroccan traditional medicine, the ripe fruits of Carum carvi L. (Apiaceae) and the leaves of Tanacetum vulgare L. (Asteraceae/Compositae), two widely available plant materials, are used as diuretics. Since, the diuretic activity of these substances has not been investigated in scientifically controlled studies, the aim of the present study was to evaluate the diuretic potential of aqueous extracts of Carum carvi fruit (caraway) and the leaves of Tanacetum vulgare (tansy) in normal rats after acute and sub-chronic oral administration. Water extracts of Carum carvi and Tanacetum vulgare (100 mg/kg) or the reference drug, furosemide (10 mg/kg) were administrated orally to male Wistar rats and their urine output was quantitated at several intervals of time after the dose. After single doses of the extracts of both caraway seeds and tansy leaves, urine output was significantly increased at all time points, and at 24 h after the dose, the total volume of urine excreted was similar for the plant extracts and furosemide. Both extracts increased urinary levels of Na(+) and K(+), to about the same extent, while furosemide increased urinary levels of only Na(+) and decreased urinary K(+). Despite changes in urinary excretion of the electrolytes, plasma Na(+) and K(+) levels were not affected by any of the three substances. In the 8-day sub-chronic study, all three substances induced significant diuresis and natriuresis; only tansy increased urinary potassium excretion. The plant extracts did not appear to have renal toxicity or any other adverse effects during the study period. In conclusion, water extracts of both Carum carvi and Tanacetum vulgare have strong diuretic action confirming their ethnopharmacological use. From the pattern of excretion of water, sodium and potassium, it may be deduced that there are atleast two types of active principals present in these extracts, one having a furosemide-like activity and the other a thiazide-like activity.

Animals↗

The analgesic effect of Carum copticum extract and morphine on phasic pain in mice.

Pain is a universal complaint, which needs further investigations for new pain relieving agents. Carum copticum (L.) Sprague ex Turrill is a plant in Umbelliferae family, which is mentioned to have some therapeutic effects on headache and joint pains in Iranian traditional literature, but there are not enough scientific reports to prove its effects on pain. So, we conducted to design an experimental clinical trial study to assess and compare the analgesic effect of ethanolic extract of Carum copticum fruit with morphine by using a tail-flick analgesiometer device. Our results indicate that the test drug produced significant increase in tail-flick latency (TFL) during 2h post-drug administration (p<0.05). The peak of the effect was observed at 45min after drug injection, which was comparable to that of 1mg/kg morphine (i.p.). Positive results in this type of analgesiometric test indicate that the antinociceptive action may be of the opoid type. The present study supports the claims of Iranian traditional medicine showing that Carum copticum extract possesses a clear-cut analgesic effect. However, further investigations are required to evaluate the efficacy and safety of this herbal medication in man.

Analgesics↗

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.

Animals↗

Molluscicidal activity of Ferula asafoetida, Syzygium aromaticum and Carum carvi and their active components against the snail Lymnaea acuminata.

The molluscicidal activity of dried root latex powder of Ferula asafoetida, flower-bud powder of Syzygium aromaticum and seed powder of Carum carvi against the snail Lymnaea acuminata was studied. The molluscicidal activity of all the three plant products was found to be both time and concentration dependent. The toxicity of S. aromaticum flower-bud powder (96 h LC(50):51.98 mg/l) was more pronounced than that of root latex powder of F. asafoetida (96 h LC(50):82.71 mg/l) and seed powder of C. carvi (96 h LC(50):140.58 mg/l). Ethanol extract was more toxic than other organic extracts. The ethanol extract of S. aromaticum (24h LC(50):83.53 mg/l) was more effective than that of F. asafoetida (24h LC(50):132.31 mg/l) and C. carvi (24h LC(50):130.61 mg/l) in killing the test animals. The 96 h LC(50) of column purified fraction of seed powder of C. carvi was 5.40 mg/l whereas those of flower-bud powder of S. aromaticum and dried root latex powder of F. asafoetida were 7.87 and 9.67 mg/l, respectively. The product of F. asafoetida, S. aromaticum and C. carvi may be used as potent molluscicides.

Animals↗

Effect of dietary caraway (Carum carvi L.) on aberrant crypt foci development, fecal steroids, and intestinal alkaline phosphatase activities in 1,2-dimethylhydrazine-induced colon carcinogenesis.

Colon cancer is one of the most common malignancies in many regions of the world and is thought to arise from the accumulation of mutations in a single epithelial cell of the colon and rectum. Caraway (Carum carvi L. Umbelliferae) is a shrub with a long history as a medicinal plant since ancient times. The effect of different doses of caraway (CC) on the formation of aberrant crypt foci (ACF) and the levels of fecal bile acids, neutral sterols, and alkaline phosphatase (ALP) activities were studied in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats. Animals were randomized into 6 groups. Group 1 served as control, and group 2 received 90 mg/kg body weight caraway orally everyday. Groups 3-6 rats were given subcutaneous injections of DMH (20 mg/kg body weight) once a week for the first 4 weeks to induce ACF. Rats in groups 4-6, in addition to DMH injections, received caraway at 30, 60, and 90 mg/kg body weight respectively p.o. everyday until the end of whole experimental period of 15 weeks. Caraway supplementation significantly reduced ACF development and also decreased the levels of fecal bile acids, neutral sterols, and tissue ALP activities. The histological alterations induced by DMH were also significantly improved. Overall, our results showed that all 3 doses of caraway inhibited tumorigenesis though the effect of the intermediary dose of 60 mg/kg body weight was more pronounced.

1,2-Dimethylhydrazine↗

Suppressive effects of caraway (Carum carvi) extracts on 2, 3, 7, 8-tetrachloro-dibenzo-p-dioxin-dependent gene expression of cytochrome P450 1A1 in the rat H4IIE cells.

Cytochrome P450 1A1 (CYP1A1) is among the cytochrome P450 classes known to convert xenobiotics and endogenous compounds to toxic and/or carcinogenic metabolites. Suppression of CYP1A1 over expression by certain compounds is implicated in prevention of cancer caused by chemical carcinogens. Chemopreventive agents containing high levels of flavonoids and steroids-like compounds are known to suppress CYP1A1. This study was carried out for assessment of the genomic and proteomic effects of caraway (Carum carvi) extracts containing high levels of both flavonoids and steroid-like substances on ethoxy resorufin dealkylation (EROD) activity and CYP1A1 at mRNA levels. Rat hepatoma cells co-treated with a CYP1A1 inducer i.e. TCDD (2, 3, 7, 8-tetrachlorodibenzo-p-dioxin) and different preparations of caraway extracts at concentrations of 0, 0.13, 1.3, and 13 microM in culture medium. After incubation (37 degrees C and 7% CO2 for 20 h), changes in EROD specific activity recorded and compared in cells under different treatments. The results show that caraway seed extract prepared in three different organic solvents suppressed the enzyme activity in hepatoma cells in a dose-dependent manner. The extracts added above 0.13 microM could significantly inhibit EROD activity and higher levels of each extract (1.3 and 13 microM) caused approximately 10-fold suppression in the enzyme activity. Accordingly, data obtained from the RT-PCR (TaqMan) clearly showed the suppressive effects of plant extract on CYP1A1-related mRNA expression. These data clearly show that substances in caraway seeds extractable in organic solvents can potentially reverse the TCDD-dependent induction in cytochrome P450 1A1.

Animals↗

Antibacterial activity of Cuminum cyminum L. and Carum carvi L. essential oils.

Essential oils extracted by hydrodistillation from fruits of Cuminum cyminum L. and Carum carvi L. were analyzed by gas chromatography (GC) and GC-mass spectrometry (MS). The main components of C. cyminum oil were p-mentha-1,4-dien-7-al, cumin aldehyde, gamma-terpinene, and beta-pinene, while those of the C. carvi oil were carvone, limonene, germacrene D, and trans-dihydrocarvone. Antibacterial activity, determined with the agar diffusion method, was observed against Gram-positive and Gram-negative bacterial species in this study. The activity was particularly high against the genera Clavibacter, Curtobacterium, Rhodococcus, Erwinia, Xanthomonas, Ralstonia, and Agrobacterium, which are responsible for plant or cultivated mushroom diseases worldwide. In general, a lower activity was observed against bacteria belonging to the genus Pseudomonas. These results suggest the potential use of the above essential oils for the control of bacterial diseases.

Anti-Bacterial Agents↗

Antioxidant and biocidal activities of Carum nigrum (seed) essential oil, oleoresin, and their selected components.

In the present study, chemical constituents of the essential oil and oleoresin of the seed from Carum nigrum obtained by hydrodistillation and Soxhlet extraction using acetone, respectively, have been studied by GC and GC-MS techniques. The major component was dillapiole (29.9%) followed by germacrene B (21.4%), beta-caryophyllene (7.8%), beta-selinene (7.1%), and nothoapiole (5.8%) along with many other components in minor amounts. Seventeen components were identified in the oleoresin (Table 2) with dillapiole as a major component (30.7%). It also contains thymol (19.1%), nothoapiole (15.2.3%), and gamma-elemene (8.0%). The antioxidant activity of both the essential oil and oleoresin was evaluated in mustard oil by monitoring peroxide, thiobarbituric acid, and total carbonyl and p-anisidine values of the oil substrate. The results showed that both the essential oil and oleoresin were able to reduce the oxidation rate of the mustard oil in the accelerated condition at 60 degrees C in comparison with synthetic antioxidants such as butylated hydroxyanisole and butylated hydroxytoluene at 0.02%. In addition, individual antioxidant assays such as linoleic acid assay, DPPH scavenging activity, reducing power, hydroxyl radical scavenging, and chelating effects have been used. The C. nigrum seed essential oil exhibited complete inhibition against Bacillus cereus and Pseudomonas aeruginosa at 2000 and 3000 ppm, respectively, by agar well diffusion method. Antifungal activity was determined against a panel of foodborne fungi such as Aspergillus niger, Penicillium purpurogenum, Penicillium madriti, Acrophialophora fusispora, Penicillium viridicatum, and Aspergillus flavus. The fruit essential oil showed 100% mycelial zone inhibition against P. purpurogenum and A. fusispora at 3000 ppm in the poison food method. Hence, both oil and oleoresin could be used as an additive in food and pharmaceutical preparations after screening.

Allyl Compounds↗

Solid phase microextraction with gas chromatography-mass spectrometry: a very rapid method for identification of volatile organic compounds emitted by Carum copticum.

The investigation of flower scent represents an important field of modern biological research which is directed towards special theories of biological recognition. The headspace solid phase microextraction coupled with gas chromatography-mass spectrometry was used to identify the volatile components of Carum copticum (C. copticum) cultivated in Iran. The compounds were identified according to their retention indices and mass spectra (EI, 70 eV). The effects of different parameters, such as the desorption time, the extraction temperature, the sample mass, the addition of salt, the pre-equilibration time and the extraction time, on the extraction efficiency were investigated. The optimized conditions were: the desorption time, 2 min; the extraction temperature, 58 degrees Celsius; the sample mass, 1.000 g in 4.0 mL 2.0 M NaCl solution; the pre-equilibration time, 25 min; the extraction time, 20 min. Finally, ten components were identified in the volatile components of C. copticum. The major components of C. copticum were thymol (68.2%), gamma-terpinene (13.9%), p-cymene (11.6%), myrcene (1.0%) and beta-pinene (0.6%). Precision of the proposed method is good and %RSD less than 14 was obtained.

Carum↗

Non-invasive localization of thymol accumulation in Carum copticum (Apiaceae) fruits by chemical shift selective magnetic resonance imaging.

Magnetic resonance imaging was used to localize the site of essential oil accumulation in fruit of Carum copticum L. (Apiaceae). A chemical shift method is described that utilized the spectral properties of the aromatic monoterpene thymol, the major component of the essential oil, to image thymol selectively. The presence of essential oil secretory structures in the fruit and an essential oil containing a high proportion of thymol were confirmed with optical microscopy and gas chromatography-mass spectrometry, respectively. Selective imaging of whole C. copticum fruits showed that thymol accumulation was localized to the secretory structures (canals) situated in the fruit wall. The technique was considered non-invasive as the seeds used in the imaging experiments remained intact and viable.

Carum↗

Dose-response efficacy of caraway (Carum carvi L.) on tissue lipid peroxidation and antioxidant profile in rat colon carcinogenesis.

Colon cancer is a leading cause of cancer death and its prevention is of great interest throughout the world. This study was conducted to examine the efficacy of different doses of dietary caraway (Carum carvi L.) on tissue lipid peroxidation (LPO) and antioxidant profile in rat colon carcinogenesis. Wistar male rats were divided into 6 groups and were fed a modified pellet diet for the whole of 30 weeks. To induce colon cancer, rats were given a weekly subcutaneous injection of 1,2-dimethylhydrazine (DMH) at a dose of 20 mg kg(-1) (based on body weight) for the first 15 weeks. Caraway was supplemented every day orally at doses of 30, 60 and 90 mg kg(-1) for different groups of rats for the total period of 30 weeks. All rats were sacrificed at the end of 30 weeks, the colons were examined visually for masses and were subsequently evaluated histologically. The results showed diminished levels of intestinal, colonic and caecal LPO products, such as conjugated dienes (CD), lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS) and also the antioxidants superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione reductase (GR) in DMH treated rats, which were significantly reversed (P<0.05) on caraway supplementation. Moreover, enhanced activity of intestinal, colonic and caecal glutathione peroxidase (GPx), glutathione S-transferase (GST) and colonic ascorbic acid and alpha-tocopherol levels were observed in carcinogen-treated rats, which were significantly (P<0.05) reduced on caraway supplementation. Thus, our study showed that caraway supplementation at a dose of 60 mg kg(-1) had a modulatory role on tissue LPO, antioxidant profile and prevented DMH-induced histopathological lesions in colon cancer rats.

Animals↗

Inhibitory effect of Carum copticum on histamine (H1) receptors of isolated guinea-pig tracheal chains.

In a previous study, the relaxant and anti-cholinergic (functional antagonism) effects of Carum copticum were demonstrated on guinea-pig tracheal chains. To elucidate the other mechanisms responsible for this relaxant effect, the inhibitory effect of this plant on histamine H1 receptors was examined in this study. The anti-histaminic effects of extracts, essential oil, 5 nM chlorpheniramine, and saline were tested by performing the cumulative log concentration-response curves of histamine induced contraction of isolated guinea-pig tracheal chains incubated with three different conditions: 1.4 microM indomethacin (group 1, n = 9); indomethacin, 1 microM propranolol, and 10 nM atropine (group 2, n = 8); and indomethacin and propranolol (group 3, n = 7). The results showed clear rightward shifts in histamine response curves obtained in the presence of extracts, essential oil, and chlorpheniramine in all three sets of experiments compared with the curves obtained in the presence of saline. The effective concentrations of histamine causing 50% of maximum response (EC50) obtained in the presence of extracts, essential oil, and chlorpheniramine in all three sets of experiments were significantly higher than those of saline (P < 0.05- < 0.001) except EC50 of macerated extract in group 1. However, maximum response to histamine obtained in the presence of extracts and essential oil were lower (P = 0.005- < 0.001) except maximum response of essential oil in group 2. In addition, the maximum responses obtained in the presence of extracts in group 2 experiments compared to the other two sets of experiments were improved. Comparison of the slope of histamine-response curves showed parallel shifts of the curves obtained in the presence of all extracts and essential oil in group 2 experiments. The results of this study indicated a competitive antagonism effect of C. copticum at histamine H1 receptors. A beta-adrenergic stimulatory effect of essential oil and an anti-cholinergic property of the plant were also suggested.

Animals↗

Cholinomimetic effects of aqueous extracts from Carum copticum seeds.

An aqueous extract from roasted seeds of Carum copticum (omum) has cholinomimetic effects. It shows muscarinic effects on rabbit duodenum, guinea-pig ileum and rat jejunum, and on the blood pressure of rat and cat. These effects are blocked by atropine. It also has a nicotinic action on the frog rectus preparation and atropinized cat blood pressure. Its effect is potentiated by physostigmine and antagonized by cholinesterase or alkalinization. Paper and gas chromatography have confirmed the presence of acetylcholine and choline in the roasted omum seed extract.

Animals↗

Inhibitory effects of caraway (Carum carvi L. ) and its component on N-methyl-N'-nitro-N-nitrosoguanidine-induced mutagenicity.

To elucidate the mechanism of antimutagenicity of caraway, we examined the effects of caraway seed extract on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced mutagenesis in DNA methyltransferase-deficient Salmonella typhimurium strains, O6-methylguanine DNA adduct formation, and thiol content in S. typhimurium cells. MNNG was highly mutagenic for ogt- strains YG7104 (ogt- ada+) and YG7108 (ogt- ada-), and it showed slightly higher mutagenicity in strain YG7100 (ogt+ ada-) than in strains TA100 and TA1535. Hot water extract of caraway seeds inhibited MNNG-induced mutation only in the ogt+ strains. In the presence of caraway extract, O6-methylguanine DNA adducts in strain YG7100 were decreased in proportion to the decrease of MNNG-induced mutagenesis. Although MNNG is known to degrade in the presence of thiols to produce methyl cation which can react with DNA, caraway had no effect on cellular concentrations of acid-soluble thiols. These results indicate that caraway does not directly inactivate MNNG and that Ogt-O6-methylguanine-DNA methyltransferase may be involved in the antimutagenic activity of caraway.

Antimutagenic Agents↗