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Effect of hydroalcoholic extract of caraway on thyroid gland structure and hormones in female rat
Abstract
Caraway is one of the medicinal plants used for digestion problems, however, it has been reported that the long term use of this plant in large doses might cause hyperthyroidism symptoms such as leanness, hair loss, severe sweating and tremulousness. Therefore, the aim of this study was to evaluate the effect of hydroalcoholic extract of caraway on the level of thyroid hormones and morphologic changes of thyroid gland in rats. For this purpose, 60 rats were divided into 5 experimental and control groups. Experimental groups were orally given 100, 400, 800 and 1600 mg/kg of extract for 45 days by gavage. The same volume of saline was given to the control group. Blood samples were taken before and after the experiments for the measurement of hormones. The rats were dissected under deep anesthesia and their thyroid glands were removed, processed and stained with H&E. Results show that T 3 and T 4 were increased and TSH was decreased significantly at high doses compared to those in the control group, but no change was observed in the structure of the gland and the size of follicles. It seems that caraway can temporally increase thyroid hormones and cause hyperthyroidism, but further studies are required to clarify the issue.
... On the other hand, non-pharmacological management of hypothyroidism involve life style modification and dietary components administration compromising vitamins, minerals and amino acids (e.g. iodine, zinc, iron, copper, tyrosine, V.D) (Abid et al, 2016) and phytotherapy including Gotu Kola (Centella asiatica) (Brown et al, 2011), Ashwagandha (Withania somnifera) (Singh et al, 2010), Guggul (Commiphora mukul) (Singh et al, 1983) and caraway (Carium carvi) (Dehghani et al, 2010). Caraway is a biennial plant, with a height 30 to 100 cm is regional to Europe and West Asia. ...
... Thirty female Wistar rats were randomly divided into five groups (n = 6 for each), as shown below. Animal dose selection was based on previous study and on our pilot study for Propylthiouracil (PTU) and Levothyroxine (LT4) (Kaur et al, 2017) as well for caraway seeds extract (Dehghani et al, 2010). Dosage administration every day acheived by oral gavage between 9.00 -10.00 a.m so that circadian variation avoided.Blood analysis done on day 15 of PTU administration to ensure that induction of hypothyroidism achieved and then at end of month after 24 hours of last dose for each group via cardiac puncture. ...
... In the present study, caraway seeds extract reported a significant elevation of T 4 and reduction of TSH mean serum level (as do LT4) in a statistically non-dose dependent manner. These results confirmed with a previous study of caraway extract activity on thyroid gland in a diabetic-rats model (Dehghani et al, 2010). Caraway seeds extract, like thyroxine was shown to enhanced the physical activity and performance of rats involved in this study, which was reduced after hypothyroidism that induced by PTU. ...
Hypothyroidism is a systemic disease resulted from anatomical or functional absence of thyroid gland. Levothyroxine (LT4) is the principal substitution treatment in hypothyroidism. Overtreatment of hypothyroidism with levothyroxine has many adverse consequences. Also, several medications, supplements and foods can interfere with the absorption and action of levothyroxine. Caraway considered one of the plants which can cause leanness, hand tremor, tachycardia, sweating,if ingested for prolong periods. These impacts are similar to that of hyperthyroid symptoms.Cariumcarviwhere extracted; chemical analysis of the extract where done (Phytochemical screening tests and Gas chromatography-mass spectrometry (GC-MS) analysis). Thyrotropic activity of ethanolic caraway seeds extract has been studied by using two doses of caraway seed extract 1000 and 2000mg/kg and compare with control group (DMSO10ml/kg), hypothyrodisim group (propylthiouracil PTU 10mg/ kg) and standard treatment therapy group (LT4 15 mcg/kg). The GC-MS analysis revealed the presence of carvone and limonene.In comparsion to hypothyroid group, the extract cause significant reduction thyroid stimulating hormone (TSH), total cholesterol (TC) levels and significant elevation in in thyroxin (T 4), deiodinase type 1 (DIO1), glucose-6-phosphatase (G6pase) levels, while malondialdhyde (MDA) were slightly reduced and catalase (CAT) slightly raised. Light microscopical observation of thyroid tissue illustrated that group which received antithyroid agent (propylthiouracil) for 14 days, show distorted and hypertrophied thyroid follicles when compared with control that show no change in thyroid follicles. After treatment of hypothyroidism with levothyroxine for two weeks, thyroid follicles return more or less to normal size. This finding consists with that of the last two groups, which received caraway seed extract at different doses for the same period. Caraway seeds extract showed stimulatory effects on the thyroid gland, suggesting its beneficial role in treating hypothyroidism.
... The iridoids of aucubine and agnoside were separated from the plant leaves up to 6%. Several studies demonstrated that phytoestrogens reduce the Spermatogenesis and gestation index (Dehghani, Panjehshahin, & Vojdani, 2010;Najafizadeh, Dehghani, Panjeh Shahin, & Hamzei Taj, 2013). Thus, the present study is aimed at investigating the effect of a hydro-alcoholic extract of Vitex agnus -castus L. leaves on the gestation indices of male rats. ...
... The estradiol level had increased insignificantly. In another study in which the effect of kiwi phytoestrogens on the male rats' spermatogenesis was investigated, the estradiol level had increased ( (Dehghani et al., 2010;Najafizadeh et al., 2013). In addition, the comparison of testosterone level results, among five groups, indicated a significant reduction. ...
... It should be mentioned that the phytoestrogen used in the present study was of genistein type in lignans Vitex, which is similar to the findings of Najafizadeh in 2013. (Dehghani et al., 2010;Najafizadeh et al., 2013). Similar to the soybean group, the prescription of Vitex extract reduced their LH level in all three doses, significantly. ...
Background: Phytoestrogens are some plant compounds with estrogenic biological effects which are found in many nutritional sources as soybean, flaxseed, and sesame. Vitex agnus-castus, also called Vitex, owns phytoestrogen properties. Studies have shown that phytoestrogens have different impacts on the gestation process and reproduction indices. Objective: The present study was aimed to investigate the effects of Vitex extract on the gestation indices in the male rat as well as studying its histological properties in the rat testicles. Materials and Methods: The hydro-alcoholic extract of Vitex (in three doses of 165, 265 and 365 mg/kg), vehicle (normal saline) and the hydro-alcoholic powder of soybean (120 mg/kg) were respectively given to understudy, vehicle and positive control groups for 49 days. After weighing the rats in the 1st and 49th days, the blood samples of all groups were taken and tested for estradiol levels, testosterones, FSH and LH. Moreover, such reproductive indices as sperm count, sperm motion, and prostate and testicle weight were studied and samples were collected for histological studies. Results: Prescription of the hydro-alcoholic extract of Vitex (in three doses of 165, 265 and 365 mg/kg) did not change the rat's weight, significantly (P-value= 0.06). Hormonal studies reduced the progesterone, LH, and FSH compared to the vehicle group, significantly (P-value<0.05). In addition, the amount of estradiol was significantly more than the vehicle group and the most effect was observed at a dose of 365 mg/kg (P-value=0.02). Histological studies showed a reduction in existing spermatozoa in the seminiferous ducts. Conclusions: This study had shown that the Vitex extract had inhibiting effects on the gestation indices in male rat and due to its destructive effects on the testicle tissues, more studies were required.
... The iridoids of aucubine and agnoside were separated from the plant leaves up to 6%. Several studies demonstrated that phytoestrogens reduce the Spermatogenesis and gestation index (Dehghani, Panjehshahin, & Vojdani, 2010;Najafizadeh, Dehghani, Panjeh Shahin, & Hamzei Taj, 2013). Thus, the present study is aimed at investigating the effect of a hydro-alcoholic extract of Vitex agnus -castus L. leaves on the gestation indices of male rats. ...
... The estradiol level had increased insignificantly. In another study in which the effect of kiwi phytoestrogens on the male rats' spermatogenesis was investigated, the estradiol level had increased ( (Dehghani et al., 2010;Najafizadeh et al., 2013). In addition, the comparison of testosterone level results, among five groups, indicated a significant reduction. ...
... It should be mentioned that the phytoestrogen used in the present study was of genistein type in lignans Vitex, which is similar to the findings of Najafizadeh in 2013. (Dehghani et al., 2010;Najafizadeh et al., 2013). Similar to the soybean group, the prescription of Vitex extract reduced their LH level in all three doses, significantly. ...
... 10 This gland is responsible for the production, storage and release of thyroid hormones triiodothyronine (T 3 ) and thyroxine (T 4 ). 11 These hormones are essential for cell growth and development. 12 One of the thyroid disorder is hypothyroidism which is defined as a deficiency in thyroid hormones production as a result of dysfunction of the synthesis and secretion of hormones. ...
The aqueous leaf extract of Achyranthes aspera was evaluated for its ameliorative effect in the regulation of hypothyroidism induced by methimazole in male albino rats. Rats were divided into four groups, three for each. Group I (control), group II (hypothyroid control) normal rats administered orally with methimazole 25 (mg/kg bwt.) for five successive days, treated group III and group IV with aqueous leaf extract of Achyranthes aspera 400 (mg/kg bwt.) for 14 and 28 days respectively, after hypothyroidism. Statistical analysis was done using student's t test. The obtained results revealed that hypothyroidism induced group II showed significant decrease in serum T 3 and T 4 (p<0.001), a significant increase in serum TSH was also observed (p<0.001), when compared to control group I. It was also observed that treated group III and group IV with aqueous leaf extract of Achyranthes aspera 400 (mg/kg bwt.) for 14 and 28 days respectively, after hypothyroidism showed significant increase in serum T 3 and T 4 (p<0.001), a significant decrease in serum TSH content was also observed, when compared with hypothyroid control group II. To conclude, aqueous extract of Achyranthes aspera leaf could be a potential therapeutic alternative for the management of hypothyroidism.
... This finding is also consistent with the existing data, observed following particular dietary guidelines, including avoidance, dietary recommendations, and lifestyle modifications for FD treatment [7,47,48]. In a recent study, various approaches were employed to determine the positive and negative effect of food on the GI tract activity, such as stimulation of the sympathetic system, increment of peripheral blood flow, thyroid hormones, basal metabolism, and cardiac palpitation, induction of the production of digestive enzymes, and accelerating gastric emptying and hypertension [49][50][51][52]. Each of these approaches, individually or in combination, can justify the effect of this diet on reducing the PDS symptoms. ...
Objectives
Postprandial distress syndrome (PDS) is associated with food indigestion. Efficacy of drugs used against PDS is limited whereas dietary modifications were shown to have important beneficial effects. Traditional Persian Medicine (TPM) sages suggested a dietary regimen known as Persian metabolic diet (PMD) for the management of PDS patients. In this study, the efficacy of PMD in alleviating the symptoms of PDS was explored.
Methods
This single-center, parallel-group, randomized clinical trial included 56 patients whom were randomly allocated to PMD group (29 participants) and Optional diet (OD) group (27 participants). They were instructed to follow the protocol for two weeks. Using a standard validated questionnaire, all outcomes were evaluated at baseline, end of the intervention period, and end of follow-up time.
Results
At the end of the intervention period, comparing the changes of severity scores between the groups showed a statistically significant difference in week 2 (p-value<0.001) and week 8 (p-value<0.001) follow-up comparing to the baseline. Similarly, at the end of the follow-up period, epigastric fullness, epigastric discomfort, and bloating were significantly improved in the PMD group (p<0.001).
Conclusions
This diet prepared based on Persian medicine seems to be effective in relieving the symptoms of patients with PDS.
... In a study by (Dehghani et al., 2010), results show that T3 and T4 were increased and TSH was decreased significantly at high doses giving orally to rats compared to those in the control group, but no change was observed in the structure of the gland and the size of follicles. It seems that caraway can temporally increase thyroid hormones and cause hyperthyroidism. ...
Fennel seeds consumption decreased the weights of body, liver, kidneys
and testes but increased thyroid gland weight of male rats.
Long-term exposure to fennel with high doses has reduced thyroid
hormones (T3 and T4) serum levels, while low doses and short-term
exposure showed non-significant effects.
Fennel consumption illustrated non-significant change in TSH serum
levels in different doses and periods of time.
Long-term exposure to fennel with high doses increased liver enzymes
(GOT, GPT, ALP) serum levels, while low doses and short-term
exposure showed non-significant effects.
Long-term exposure to fennel with high doses increased renal function
tests (Urea, Total protein, Creatinine) serum levels, while low doses and
short-term exposure showed non-significant effects.
Long-term exposure to fennel with high doses decreased testes hormone
(Testosterone) serum levels, while low doses and short-term exposure
showed non-significant effects.
Fennel seeds consumption for short and long periods of time and
in all concentrations caused empty follicles from colloid,
and damage of thyroid gland. Liver sections showed sinusoidal . .
..dilatation degeneration effect in the renal epithelial cells of both distal
. and proximal convoluted tubules. Testis showed seminiferous tubules
..with No sperms appear inside the lumen certain. Wide areas of necrosis
. of spermatogonia cells in addition to necrosis in all the organs above.
... The results of the present study which showed reduction in thyroid hormones T3 and T4 agreed with results of another previous study by Kooti et al. (2015) after administration with alcoholic extract of celery (member in Apiaecea family) with doses (50, 100, 200mg/ kg) in male rats, but it caused significant increase in TSH, which disagrees with the present study, as it illustrated no change in TSH values. These results disagreed with consequence of Dehghani et al. (2010) whom exposed female rats to (100, 400, 800 and 1600 mg/kg) hydroalcoholic extract of caraway for 45 days, which raised T3 and T4 levels while TSH was decreased significantly at high doses compared to those in control groups. It also disagreed with Parvinroo et al. (2014), who fed male rats with a diet containing 10% seeds of anise, fennel and ajowan (all members of the same family). ...
In various parts of the world Fennel seeds Foeniculum vulgare has been used in a herbal medicine. The present study aims to shed light on fennel's side effects in male rats in the weights, hormonal, histological changes and some of the physiological parameters of thyroid and testes. About 60 Spargue-Dawley albino adult male rats were daily fed with fennel pellet in three different doses (50, 100, 200)gm/kg bw for three different periods of time (10, 20, 30) days. After end of each experiment animals were weighed then it scarified for blood and tissue collection, blood collected by heart puncture then it centrifuged for serum separation and kept at -80oC to hormonal, biochemical analysis and some histological standards, then thyroid and testes were excised and fixed in neutral buffered 10% formalin for histological preparation. The results showed that increased doses of fennel consumption and treatment duration statistically caused Highly significant increase (p<0.01) in thyroid weights in experimental treated groups (7, 8, 9, 10, 11, 12) while group (5 and 6) showed significant increase (p<0.05) compared to the control group. No changes illustrated in values of Thyroid stimulating hormone(TSH) in all periods of time and in all concentrations of fennel in comparison with the control group. Significant (p<0.05) decrease in Triiodothyronine(T3) and Thyroxin(T4) hormone serum levels in treated groups (7, 8, 9, 10, 11, 12) compared to the control group. Significant (p<0.05) decrease in both left and right testes weights of fennel treated group (12) in comparison with the control group. Significant (p<0.05) decrease in Testosterone serum levels of fennel treated groups (8, 9, 10, 11, 12) compared to the control groups with the increase of fennel doses and treatment duration. Histological study of the organs demonstrated histological changes after an exposure to fennel for short and long periods of time and in all concentrations. Thyroid gland sections showed certain follicles empty from colloid, degenerated follicles and necrosis. Testes sections showed seminiferous tubules with certain degeneration and necrosis of spermatogonia cells besides necrotic debris inside the lumen, no sperms appear inside the lumen.
... According to the research, caraway increases T3 and T4 hormones and reduces TSH (28), which increases the metabolism of fat. ...
... For example, caraway is one of the medicinal plants used for digestion problems, as it is known to possess anti-colitic activity (Keshavarz et al. 2013), it enhances body exposure to paracetamol in mice (Samojlik et al. 2012), and it inhibits growth of many bacteria and fungi (Seidler-Łożykowska et al. 2013). At the same time, caraway can temporally increase thyroid hormones and cause hyperthyroidism, which was demonstrated for rats (Dehghani et al. 2010). Caraway oil and its principal components, carvone and limonene, are anticarcinogenic (Zheng et al. 1992;Crowell 1999;Kaefer, Milner 2011). ...
The application of caraway essential oil and its main components, carvone and limonene, to plant surface caused significant changes in aphid probing at the level of non-vascular tissues as well as sieve elements. On treated plants, probes were short and non-probing intervals were long, phloem phase was short and sustained sap ingestion periods occurred sporadically. The deterrent activity of caraway oil is determined mainly by the content of carvone that has the most significant impact on aphid probing behavior. The impediment of aphid probing at the pre-ingestive (pre-phloem) and/or ingestive (phloem) phases revealed the passage of compounds through the plant surface and distribution within tissues in a systemic way.
... Similar results have been observed in different plant extracts such as Caraway [38], Everyouth and Dreamshape [39]. Also Ficus carica leaf extracts showed similar changes in the levels of T3 and T4, where TSH level was not investigated [40]. ...
Objective: To investigate the effect of aqueous extract of Murraya koenigii leaves on some
haematological, hormonal and serum lipid parameters in rats.
Methods: We evaluated whether oral administration of Murraya koenigii affected the
haematological, hormonal and lipid parameters. After 7 days of oral administration of 250 mg/
kg and 500 mg/kg body weight, other profiles were investigated.
Results: The results showed that the extract administered significantly increased (P < 0.05)
packed cell volume, haemoglobin concentration, red blood cell, mean corpuscular hemoglobin,
mean corpuscular hemoglobin concentration, mean corpuscular volume and decreased the
platelet count (P < 0.05) at the dose of 250 mg/kg and 500 mg/kg body weight when compared
with control. The extract significantly increased (P < 0.05) white blood cell count at all doses
administered when compared with control. Results showed that thyronine and thyroxine were
increased, while thyroid stimulating hormone was decreased significantly (P < 0.05) at high
doses compared. The recorded data in the present study showed that the testosterone value was
reduced significantly (P < 0.05) from control value. Also the extract significantly reduced (P <
0.05) the total cholesterol concentration and low density lipoproteins cholesterol concentration
in the serum while it had no significant effect on serum high density lipoprotein cholesterol
concentration at all doses administered.
Conclusions: This study suggests that the extracts may have beneficial effect on serum
cholesterol concentration, can act as a stimulant to thyroid functions as well as in anemia and
immunity dependent disorders and also as a potent contraceptive.
... Prior studies revealed that hyperthyroidism is linked to a rise in MPV (mean platelet volume) levels and a decline in PDW levels [176]. In addition, administration of a hydro-alcoholic extract of caraway (1600 mg/kg) displayed a hyperthyroidism influence through escalation in T3 and T4 levels, and a reduction in TSH levels [177]. Also, the weight of rats in the caraway extract group was remarkably lower than the control group, which shows the weight lowering effect of caraway extract. ...
The seeds of caraway (Carum carvi L.), a potent medicinal plant, are traditionally used for inducing weight loss. In this study, the antiobesity properties of caraway aqueous extract (CAE) at 30. mL/day are examined in a randomized, triple-blind, placebo-controlled clinical study. At baseline, 70 overweight and obese, healthy, aerobic-trained, women were randomly assigned to two groups (n. =. 35. per group). After 12. weeks, the CAE group, compared with placebo, showed a significant decrease in weight, body mass index (BMI), body fat percentage, and anthropometric indices. No changes were detected in the clinical and para-clinical assessments of participants. The findings show that dietary CAE with no limit in diet, when combined with physical activity, is of value in the treatment of obesity in women, lowering their weight, BMI, body fat percentage, and body size, and has no negative clinical effects. This trial is registered as NCT01833377.
... In the present study the K. alvarezii decreased the serum concentrations of both the thyroid hormones, T3 and T4, indicating a hypothyroid condition. As both T3 and T4 were decreased, it appears that algal extract inhibits T4 synthesis both at the glandular level (the only source for T4 generation) and at the level of peripheral conversion of T4 to T3, the major source of the latter hormone 3 . From the results, it is evident that administration of individual plant material reversed the changes produced by exogenous thyroxin in the concentrations of serum T3 and N. Nagarani et al., / TBAP 4 (4) 2014 262 -271 268 T4, which is similar to earlier observations with other plants 27 . ...
This study explored the constitutive oxygenated steroids of Kappaphycus alvarezii growing in southeast coast of India and evaluated the effect of methanol extract in serum lipid profile and thyroid hormone activity in male rats. Chemical structures of the isolated compound from the thalli of K. alvarezii were established by spectral techniques (UV, 1H NMR). In vivo effects were investigated for the two methanol extracts 100 and 200 mg/kg in male rats, to determine lipid profile and thyroid hormone activity by chemiluminescence's method. The 1H NMR studies revealed the signals in the region 0.5 to 2.0 ppm suggesting the presence of steroidal identity in the methanol extract. Serum LDL level decrease from 46 mg/dl to 42.5 mg/dl. The result substantiate that the daily intake of this alga can lower the cholesterol and serum T3 level. The alga can be considered for, therapeutic application, for thyroid hormone disorders and obesity problems.
... characteristics, fire is warm and dry, air is warm and wet, water is cold and wet, and soil is cold and dry. After integration of these four elements in different quantities, one or two qualities will be dominant in subjects (or objects). This predominant quality (or qualities) increase in their body weight compared to untreated diabetic rats (9). In 2010, Dehghani, et al. showed that daily use of hydroalcoholic extract of caraway in rats, causes significant weight loss, an increase in T 3 and T 4 hormones and a decrease in thyrotropin levels (10). More recent findings show that piperine, an active ingredient in black pepper, can induce weight loss with different mechanisms including: increase in thyroid ...
This study was aimed to evaluate the effects of diets containing some hot and cold temperament herb seeds according to Iranian traditional medicine (ITM) on some metabolic parameters in acute (24 h) and sub-acute (7 day) experiments that were performed on rats. For each experiment, effects of diets containing 10% herb seeds in category of hot (anise, fennel, ajowan) and cold (cucumber, watermelon, pumpkin) temperaments were analyzed on body weight gain, food intake, water consumption, urine output, serum glucose (SG) and insulin levels of rats. In the acute experiment, anise or fennel fed groups showed a significant decrease in food intake and there were not any changes in other parameters. The hot temperament groups in comparison with the cold temperament ones showed a significant decrease in food intake and a significant increase in SG level. In the sub-acute experiment, anise and fennel fed groups had a significant decrease in body weight gain on the 4thday. On the 7th day, the anise fed group experienced a significant decrease in body weight gain and a significant increase in SG levels. The groups that were fed hot temperament diets compared to the ones that consumed cold temperament diets showed a significant decrease in body weight gain and food intake rates and a considerable increase in SG levels. Considering the findings of this study, one can conclude that it is possible that hot temperament herbs such as anise and fennel be useful for humans for certain conditions such as weight control.
... A previous report showed that hyperthyroidism is associated with an increase in MPV and a decrease in PDW (Ford and Carter 1990). Caraway showed a hyperthyroidism effect through increasing T3 and T4, and decreasing TSH (Dehghani et al., 2010). Consistent with these reports, the present results with the administration of CAE suggest a possible anti-hypothyroidism effect in humans. ...
Carum carvi L. (Apiaceae) is known as caraway, and its derivatives find wide medicinal use for health purposes, including for gastrointestinal problems and obesity. Since there is inconsistency among the reports on the safety of this plant in humans, this research was aimed at assessing the safety of a characterized caraway aqueous extract (CAE) in a randomized, triple-blind, placebo-controlled study. Seventy, overweight and obese, healthy women were randomly assigned into placebo (n = 35) and plant extract (n = 35) groups. Participants received either 30 ml/day of CAE or placebo. Subjects were examined at baseline and after 12 weeks for changes in heart rate, blood pressure, urine test, 25-item blood chemistries, and general health status. No significant changes of blood pressure, heart rate, urine specific gravity, and serum blood tests were observed between the two groups before and after treatment. However, in the complete blood count test, red blood cell levels were significantly (p < 0.01) increased, and platelet distribution width was significantly decreased after the dietary CAE treatment, as compared with placebo. No negative changes were observed in the general health status of the two groups. This preliminary study suggests that the oral intake of CAE appears to be without any adverse effects at a dosage of 30 ml daily for a period of 12 weeks. Copyright © 2014 John Wiley & Sons, Ltd.
Talinum triangulare (waterleaf) supplementation in broiler production had been reported to effects on reproduction and thyroid function which is important in the maintenance of normal reproductive function. The effect of waterleaf supplementation on serum levels of thyroid stimulating hormone (TSH) and egg hatchability of Isa brown pullets was studied. Three experimental groups (T1, T2 and T3) represented the waterleaf-supplemented; and control (un-supplemented), respectively. Extracts from dried or freshly harvested samples (T1 or T2) of T. triangulare were administered in drinking water at the rate of 62.5, 250 and 1000 mg/L for a, b, and c subgroups; (T1a, T1b, T1c, T2a, T2b, T2c) and 0 mg/L for the control (T3), each was further replicated three times. A total of 210 pullets and 21 cocks were randomly allocated to 21 replicate experimental groups. Feed was administered at the rate of 120g/bird daily, and water was provided ad libitum for a period of 5 months. Blood samples were collected from three layers per replicate and sera harvested at days 60 and 120 for TSH assay. Eggs weighing between 50-60g were selected and set in locally-fabricated incubator for hatching on day three post-oviposition. Waterleaf extract at inclusion levels 250 and 1000 mg/L. Percentage hatchability of the eggs also improved egg hatchability in Isa-brown layers.
Assessment of genetic diversity for various traits would contribute in hybridization projects in order
to recover aspired recombinants. Therefore, metroglyph analysis and ANOVA were conducted out to
estimate genetic diversity among seven caraway genotypes. Field experiment was applied in winter
season of 2011/2012 with three replicates. Consequently, data were recorded on plant height, branches
no., umbels no. umbels diameter, no. of umbellets and plant yield. Results showed that allotting of index
scores for each trait of seven caraway genotypes represented the worth of the genotype in respects
to the trait which the performance of genotype is represented by total index score for all traits of that
genotype. Thus, Bery and Mosul genotypes ascertained the highest index scores of 16, for each one.
Moreover, Metroglyph scatter diagram revealed three groups of caraway genotypes. Therefore, it
could be concluded that metroglyph technique simply classified genotypes to groups and had potentiality
to interpret genotypes performance regarding the index scores. Thus, it could be recommended to
apply crossing or hybridization between individuals from different groups alternatively to individuals
from same group. Genotypes of Bery, Mosul, Sury and selectedF1 (Group2), and Balady (Group3)
were distinct which possible to apply crossing between one of group2 individuals with another one of
group3.
The aim of present study was to investigate the effect of dietary cornelian cherry fruit (CCF) on plasma lipids, cortisol, T3 and T4 levels. Thirty six male hamsters were divided into four groups; Group1 (control) fed basal diet without CCF supplementation, group 2 which fed 5g CCF only at first daily meal, group3 which fed 10g CCF, at first and second daily meals and group 4 which fed 15g CCF, at first, second and third daily meals, for 20 continuous days. Dietary CCF caused significant changes in plasma total cholesterol (TC), triglyceride, high density lipoprotein-C (HDL-C) and low density lipoprotein-C (LDL-C) (P<0.01); TC and LDL-C are decreased in groups 2, 3 and 4, when compared with control (group 1), whereas triglyceride was increased in CCF supplemented groups (groups 2, 3, and 4). HDL-C was greater in groups 3 and 4, when it compared with control and group 2. The cortisol level was lower for groups 2, 3 and 4, when compared with control. But there were no any significant changes for thyroid hormones (T3 and T4) between experimental groups. It was concluded that dietary cornelian cherry fruit supplementation has hypolipidemic effect due to declining total cholesterol and LDL-C levels. Also, it can increase HDL-C (good cholesterol) and decrease cortisol level, without any considerable effect on thyroid hormones (T3 and T4) level. Dietary supplementation of cornelian cherry fruit for two meals daily is suggested to more efficient hypolipidemic effect.
Dehghani, F., Panjehshahin, M.R., Mirzaee, Z. and Mehrabani, D. 2005. Effect of Foeniculum vulgare organic extract on blood sex hormones and reproductive tissues of male rats. J. Appl. Anim. Res., 27: 17–20.To determine the effect of F. vulgare on reproductive system in male rats, forty male Sprague-Drawly rats were randomly placed in 4 equal groups. The control group received water and the remaining groups received 100, 250 and 500 mg/kg of organic extract of F. vulgare for 30 days. The animals were bled before and after medications and the blood, estrogen and testosterone levels were recorded. On day 30, the rats were sacrificed and dissected for histopathological study. Increase in the dose of F. vulgare administered to male rats resulted in a significant increase in estradiol and decrease in testosterone serum levels. Spermatocyte change from spherical to fussy form shape was visible in seminiferous tubules. Many nuclei in these cells were in metaphase stage. In higher doses of F. vulgare, hyalinizations of the tubules were also observed. It appears that F. vulgare can induce inhibitory effects on spermatogenic lineage in male rats.
Background: Foods contain nonnutritional phytochemicals that may affect human health. The effect of phytochemicals on sperms is controversial. Objective: To determine whether kiwi (Actinidia chinensis) extract can change sperm quality and the blood level of sex hormones. Methods: 40 male rats were divided into 4 groups; 3 experimental groups were fed with 75, 100, or 150 mg/kg of hydroalcoholic extract of kiwi and the control group was fed with the solvent for 50 days each. Blood samples were taken and the levels of estradiol and testosterone were measured. The number of sperms and the percentage of motile sperms in semen samples were also calculated. Results: The level of testosterone and sperm count were decreased significantly in groups treated with 150 mg/kg of kiwi extract. The estradial level also was decreased in groups treated with 100 and 150 mg/kg at the extract. Conclusion: It seems that hydroalcoholic extract of kiwi has deleterious effects on spermatogenesis. It is therefore, recommended to use it with caution if there is a reproductive problem.
Thyroid hormone (T3) regulates growth, development and differentiation. These activities are mediated by nuclear thyroid hormone receptors (TRs), which belong to the steroid/thyroid hormone receptor superfamily of ligand-dependent transcription factors. In an effort to study the mechanism of target genes regulation and their physiological significance after T3 treatment in a TR alpha-overexpressing hepatoma cell line (HepG2-TR alpha), c-DNA microarrays were performed. The data demonstrated that approximately 149 genes represented were positively regulated by T3, including fibrinogen, transferrin, fibronectin (FN), androgen receptor (AR)-associated protein (ARA70), and dehydroepiandrosterone sulfotransferase family 1A member 2 (SULT2A1). To further confirm the microarray results, a quantitative-reverse transcription polymerase chain reaction (Q-RT-PCR) was applied. The protein synthesis inhibitor, cycloheximide was used to determine whether the regulation was direct or indirect. A promoter assay further showed that T3 regulation was largely at the level of transcription. Although those genes were isolated from a human tumor cell line, they are regulated similarly in rats and humans. These results indicate that T3 might play an important role in the process of blood coagulation, inflammation, metabolism and cell proliferation. This may help to explain the association between thyroid diseases and the mis-regulation of the inflammatory and clotting profiles evident in the circulatory systems of these patients.
The iodothyronine deiodinases initiate or terminate thyroid hormone action and therefore are critical for the biological effects mediated by thyroid hormone. Over the years, research has focused on their role in preserving serum levels of the biologically active molecule T(3) during iodine deficiency. More recently, a fascinating new role of these enzymes has been unveiled. The activating deiodinase (D2) and the inactivating deiodinase (D3) can locally increase or decrease thyroid hormone signaling in a tissue- and temporal-specific fashion, independent of changes in thyroid hormone serum concentrations. This mechanism is particularly relevant because deiodinase expression can be modulated by a wide variety of endogenous signaling molecules such as sonic hedgehog, nuclear factor-kappaB, growth factors, bile acids, hypoxia-inducible factor-1alpha, as well as a growing number of xenobiotic substances. In light of these findings, it seems clear that deiodinases play a much broader role than once thought, with great ramifications for the control of thyroid hormone signaling during vertebrate development and metamorphosis, as well as injury response, tissue repair, hypothalamic function, and energy homeostasis in adults.
The biosynthesis of the monoterpenes limonene and carvone in the fruit of caraway (Carum carvi L.) proceeds from geranyl diphosphate via a three-step pathway. First, geranyl diphosphate is cyclized to (+)-limonene by a monoterpene synthase. Second, this intermediate is stored in the essential oil ducts without further metabolism or is converted by limonene-6-hydroxylase to (+)-trans-carveol. Third, (+)-trans-carveol is oxidized by a dehydrogenase to (+)-carvone. To investigate the regulation of monoterpene formation in caraway, we measured the time course of limonene and carvone accumulation during fruit development and compared it with monoterpene biosynthesis from [U-14C]Suc and the changes in the activities of the three enzymes. The activities of the enzymes explain the profiles of monoterpene accumulation quite well, with limonene-6-hydroxylase playing a pivotal role in controlling the nature of the end product. In the youngest stages, when limonene-6-hydroxylase is undetectable, only limonene was accumulating in appreciable levels. The appearance of limonene-6-hydroxylase correlates closely with the onset of carvone accumulation. At later stages of fruit development, the activities of all three enzymes declined to low levels. Although this correlates closely with a decrease in monoterpene accumulation, the latter may also be the result of competition with other pathways for substrate.
Petasites hybridus is used in Chinese herbal medicine. S-petasin is a bioactive compound isolated from leaves or roots of Petasites hybridus. S-petasin has been used to relieve gastrointestinal pain, lung disease, and spasms of the urogenital tract. However, the side effect of S-petasin on endocrine systems are still not clear. This study explored the effects of S-petasin on the release of corticosterone in vivo and in vitro. An intravenous injection of S-petasin (10 microg/kg) decreased both basal and adrenocorticotropin (ACTH)-induced plasma corticosterone concentration in male rats. In vitro, S-petasin (3 x 10(-6) - 10(-4) M) caused a significant reduction of basal and ACTH-stimulated release of corticosterone from the enzymatically dispersed rat zona fasciculata-reticularis (ZFR) cells in a dose-dependent manner. In order to study possible mechanisms, ZFR cells were incubated with S-petasin (10(-5) M) in the presence or absence of forskolin (adenylate cyclase activator, 10(-6) - 10(-4) M), 8-Br-cAMP (a cAMP analogue, 10(-6) 10(-4) M), 25-OH-cholesterol (pregnenolone biosynthesis precursor, 10(-5) M) combined with trilostane (a blocker of 3beta-hydroxysteriod dehydrogenase, 3beta-HSD, 10(-6) M) and deoxycorticosterone (corticosterone biosynthesis precursor, 10(-9) - 10(-6) M) at 37 degrees C for 1h. The concentration of pregnenolone and corticosterone in media were measured by radioimmunoassay. The stimulatory effects of corticosterone secretion induced by forskolin (10(-5) - 10(-4) M), 8-Br-cAMP (10(-5) - 10(-4) M) and deoxycorticosterone (10(-7) - 10(-6) M) were reduced by S-petasin at 10(-5) M. The stimulatory effects of pregnenolone secretion induced by 25-OH-cholesterol combined with or without trilostane was reduced by S-petasin at 10(-5) M. These results suggest that S-petasin inhibits the production of corticosterone from rat ZFR cells in part through decreasing the activities of adenylyl cyclase, P450scc and 11beta-hydroxylase.
Findings from a recent large study suggest that perchlorate at commonly occurring exposure concentrations may decrease thyroid hormone levels in some women. Decreases in thyroid hormone seen with perchlorate exposure could be even greater in people with concomitant exposure to agents such as thiocyanate that may affect the thyroid by mechanisms similar to those of perchlorate.
We used data from the National Health and Nutrition Examination Survey to assess the impact of smoking and thiocyanate on the relationship between urinary per-chlorate and serum thyroxine (T(4)) and thyroid-stimulating hormone (TSH).
In women with urinary iodine levels < 100 microg/L, the association between the logarithm of perchlorate and decreased T(4) was greater in smokers [regression coefficient (beta) = -1.66, p = 0.0005] than in nonsmokers (beta = -0.54, p = 0.04). In subjects with high, medium, and low cotinine levels, these regression coefficients were -1.47 (p = 0.0002), -0.57 (p = 0.03), and -0.16 (p = 0.59). For high, medium, and low thiocyanate tertiles they were -1.67 (p = 0.0009), -0.68 (p = 0.09), and -0.49 (p = 0.11). Clear interactions between perchlorate and smoking were not seen with TSH or with T(4) in women with urinary iodine levels > or = 100 microg/L or in men.
These results suggest that thiocyanate in tobacco smoke and perchlorate interact in affecting thyroid function, and this effect can take place at commonly occurring perchlorate exposures. Agents other than tobacco smoke might cause similar interactions, and further research on these agents could help identify people who are particularly susceptible to perchlorate.
The effect of the traditional herbal medicine, Shakuyaku-Kanzo-To (SK), which contains Shakuyaku (S) and Kanzo (K) in equal amounts, on serum testosterone levels was investigated in androgen-sterilized rats. They were given orally SK [0, 22.5, 45, 90 and 180 mg/kg body weight (b.w.)] and S or K (0, 11.25, 22.5, 40 and 90 mg/kg b.w.) in 2 ml of water daily for 2 weeks. Dose-dependent decreases in free serum testosterone (T) levels were found in the administration of SK. Total serum T levels in the administration of SK and S decreased in a dose-dependent manner. K decreased total serum T levels slightly in 11.5 and 22.5 mg/kg doses but showed the dose-dependent increase in much higher doses, the extent of which was much less than that of the decrease in S. Serum estradiol/T (E2/T) ratios were significantly elevated in 45 to 180 mg/kg doses of SK, 90 mg/kg dose of S and 11.25 to 90 mg/kg doses of K. Serum LH and FSH levels were not changed by SK, S and K. Oophorectomized rats were similarly given SK (0, 90 and 180 mg/kg b.w.) and S or K (the half doses of SK). There were no changes in serum T, LH and FSH levels in all given doses. Thus, one of the mechanisms for SK to lower serum T levels is the direct action on the ovary to stimulate the aromatase activity, resulting in decreasing the T secretion and this is the additive effects of S and K.
Limonene and related monoterpenes display compelling anticarcinogenic activity. The mechanism(s) that underline this activity is/are as yet unknown. One attractive possibility is that the monoterpenes interact with the RAS signal transduction pathway. The monoterpenes have been shown to impair incorporation of mevalonic acid-derived isoprene compounds, that is farnesyl pyrophosphate, into RAS and RAS-related proteins. As farnesylation is critical for RAS's membrane localization and function, the isoprenylation pathways have received attention as potential targets of anti-RAS pharmacological maneuvers. We have expanded on prior studies and demonstrate that one of limonene's metabolic derivatives, perillyl alcohol, decreases the levels of antigenic RAS in the human-derived myeloid THP-1 and lymphoid RPMI-8402 leukemia cell lines. Both limonene and perillyl alcohol decrease levels of 35[S] methionine labeled RAS proteins in cells that have been pulsed with radiolabeled methionine for four hours. In contrast, lovastatin, which inhibits hydroxymethylglutaryl coenzyme A reductase and thus depletes cells of farnesyl pyrophosphate, does not diminish levels of total antigenic RAS but rather results in a shift in the RAS protein; levels of farnesylated RAS decrease whereas levels of unmodified/unfarnesylated RAS increase. As limonene and perillyl alcohol do not induce such a shift we conclude that these monoterpenes decrease farnesylated RAS protein levels by a mechanism that is clearly distinct from that of either depleting cells of farnesyl pyrophosphate or inhibiting the enzyme farnesyl protein transferase that catalyzes the posttranslational farnesylation of RAS. These findings are discussed with respect to implications for the monoterpenes to alter RAS protein synthesis and degradation. The results of these studies will likely impact the inclusion of the monoterpenes in clinical anticancer trials.
d-Limonene produces tumors only in the kidneys of male rats in association with hyaline-droplet nephropathy, which is due to the accumulation of the rat-specific, low molecular weight protein alpha(2u)-globulin in the P2 segment cells of renal proximal tubules. Human urine contains no alpha(2u)-globulin and, compared with the male rat, much less protein and almost no low molecular weight protein. Genotoxicity tests for d-limonene are negative, and the mechanism of tumorigenesis involves tumor promotion and enhanced cell proliferation. There is no risk of cancer for humans from d-limonene, since the binding of d-limonene to alpha(2u)-globulin would not occur.
Recently, considerable attention has been focused on certain environmental contaminants--"endocrine disruptors"--of industrial origin that may mimic the action of sex hormones. Natural compounds and their effects on other types of hormonal activity (eg, on adrenal or thyroid function) have for some reason not provoked similar attention. As exemplified by tributyltin and certain bioaccumulating chlorinated compounds, available evidence indicates that "endocrine disruption" caused by xenobiotics is primarily an ecotoxicologic problem. In mammals, certain phenylmethyl-substituted siloxanes have been found to be by far the most potent endocrine disrupters among various synthetic xenobiotics. On the other hand, it has not been possible to scientifically substantiate either certain alarming reports of powerful synergistic effects between chlorinated pesticides or the alleged adverse effects on the male reproductive tract in rodents (induced by alkylphenols and plasticizers at extremely low exposures). Whereas there is compelling evidence that estrogens in certain foods and herbal medicines can induce hormonal changes in women as well as overt toxicity in men, existing data are insufficient to support a causal relationship between exposure of the general human population to nonpharmaceutical industrial chemicals and adverse effects operating via the endocrine system. Moreover, in terms of magnitude and extent, all such exposures to so-called endocrine disruptors are dwarfed by the extensive use of oral contraceptives and estrogens for treatment of menopausal and postmenopausal disorders. Also, the exposure to hormonally active xenobiotics is virtually insignificant when compared with the intake of the phytoestrogens that are present in food and beverages, and it is even more insignificant when compared with certain herbal potions used in "alternative medicine." Furthermore, while there has been much concern about negligible exposures to xenobiotics with weak hormonelike activities, the potent endocrine disruptor licorice is freely given to children. Long-term exposure to this substance induces severe toxic symptoms of mineral corticoid hormone imbalance. Although exposures to xenobiotics and many natural compounds occur by identical routes of administration and may contribute to the same toxicological end point, they are, regrettably, judged by completely different standards. As is the case with all other chemicals, rational risk assessment and risk management of man-made and natural endocrine modulators must be based on the mode of action and dose-response relationships. Such end points as the induction of reproductive developmental effects, cancer, etc, relating to actual exposures must also be taken into consideration.
The framework developed by the International Programme on Chemical Safety (IPCS) for assessing the mode of action of tumour induction of chemicals in experimental animals has been illustrated with d-limonene, sodium saccharin, di(2-ethylhexyl)phthalate (DEHP) and sulfamethazine as examples. d-Limonene causes renal tumours only in male rats through a response associated with alpha(2u)-globulin. Sodium saccharin induces urinary bladder tumours only in male rats through formation of a urinary precipitate causing erosion of the bladder surface and extensive regenerative hyperplasia. DEHP causes liver tumours in rats and mice through activation of the receptor PPAR alpha leading to peroxisome proliferation and hepatocellular proliferation. Sulfamethazine induces thyroid follicular cell tumours in rats and mice through a mechanism involving altered thyroid hormone homeostasis.
The weight-reducing herbal medicines "Dream Shape" and "Ever Youth" became available in Japan in 2000. Herein, we describe 12 patients who developed thyrotoxicosis after taking them. The thyroid hormone content of 1 capsule or tablet of herbal medicine, measured following Pronase digestion and ethanol extraction, was approximately 1 mug of triiodothyronine and 3 to 4 mug of thyroxine. Two of us took 10 capsules or tablets of Dream Shape or Ever Youth, and changes in thyroid hormone levels were observed during the first 24 hours. Serum free triiodothyronine levels began to rise 2 hours after ingestion and reached peak levels at 4 to 8 hours; changes in free thyroxine and thyrotropin levels were small during the first 24 hours. Similar herbal medicines may have been distributed to other countries via the Internet. Resultant factitious thyrotoxicosis can create diagnostic and therapeutic confusion, particularly in patients with thyroid disease.
Thirty-one novel derivatives of carvone, carveol, and limonene were designed and synthesized using L-carvone as a starting material via chlorination, nucleophilic substitution, and reduction. The structures of these derivatives were characterized by MS and 1H NMR. The antiproliferative effect was evaluated in human prostate cancer LNCaP cells. L-carvone, L-carveol, and L-limonene were weak cell growth inhibitors and introduction of 4-(2-methoxyphenyl)piperazine to carvone, carveol or limonene significantly increased their antiproliferative effect. The antiproliferative effect was correlated with ERK activation and p21(waf1) induction.
Many terpenes are used therapeutically, and as flavor and fragrance materials. (R)-(-)-Carvone, the main constituent of spearmint oil, and (S)-(+)-carvone, found as major component of caraway and dill seed oils, have several applications and are used in cosmetic, food, and pharmaceutical preparations. In this study, the effect of enantiomers of carvone on the central nervous system (CNS) was evaluated in mice. The LD50 value was 484.2 mg/kg (358.9-653.2) for (S)-(+)-carvone, and 426.6 (389.0-478.6) mg/kg for (R)-(-)-carvone. Both enantiomers caused depressant effects, such as decrease in the response to the touch and ambulation, increase in sedation, palpebral ptosis, and antinociceptive effects. (S)-(+)- and (R)-(-)-carvone caused a significant decrease in ambulation. (R)-(-)-Carvone appeared to be more effective than its corresponding enantiomer at 0.5 and 2.0 h after administration. However, (S)-(+)-carvone was slightly more potent at 1 h. In potentiating pentobarbital sleeping time, (R)-(-)-carvone was more effective than (S)-(+)-carvone at 100 mg/kg, but was less potent at 200 mg/kg compared to the (+)-enantiomer, indicating a sedative action. (S)-(+)-Carvone at the dose of 200 mg/kg increased significantly the latency of convulsions induced by PTZ and PIC, but (R)-(-)-carvone was not effective against these convulsions. These results suggest that (S)-(+)-carvone and (R)-(-)-carvone have depressant effect in the CNS. (S)-(+)-Carvone appears to have anticonvulsant-like activity.
D-limonene is one of the most common terpenes in nature. It is a major constituent in several citrus oils (orange, lemon, mandarin, lime, and grapefruit). D-limonene is listed in the Code of Federal Regulations as generally recognized as safe (GRAS) for a flavoring agent and can be found in common food items such as fruit juices, soft drinks, baked goods, ice cream, and pudding. D-limonene is considered to have fairly low toxicity. It has been tested for carcinogenicity in mice and rats. Although initial results showed d-limonene increased the incidence of renal tubular tumors in male rats, female rats and mice in both genders showed no evidence of any tumor. Subsequent studies have determined how these tumors occur and established that d-limonene does not pose a mutagenic, carcinogenic, or nephrotoxic risk to humans. In humans, d-limonene has demonstrated low toxicity after single and repeated dosing for up to one year. Being a solvent of cholesterol, d-limonene has been used clinically to dissolve cholesterol-containing gallstones. Because of its gastric acid neutralizing effect and its support of normal peristalsis, it has also been used for relief of heartburn and gastroesophageal reflux (GERD). D-limonene has well-established chemopreventive activity against many types of cancer. Evidence from a phase I clinical trial demonstrated a partial response in a patient with breast cancer and stable disease for more than six months in three patients with colorectal cancer.
Biosynthesis of the monotrepenes limonene and carvone in the fruit of caraway
- Hj Bouwmeester
- J Gershenzon
- Mc Konings
- Croteau
Bouwmeester, HJ; Gershenzon, J; Konings, MC and Croteau, R (1998). Biosynthesis of the monotrepenes limonene and carvone in the fruit of caraway. Plant Physiol., 117: 901- 912