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Evaluation of the Prophylactic Effect of Fennel Essential Oil on Experimental Osteoporosis Model in Rats
Abstract
The water-distilled essential oil of Iranian fennel seeds ( Foeniculum vulgare Mill.) was investigated for its composition and anti-osteoporotic activities in ovariectomized rat osteoporosis model. After oil analysis by GC/MS, 15 components were identified in the oil. Among them, trans-anethole (81.1%) and fenchone (9.2%) were the major components. Healthy female albino rats were divided into five groups of six animals each including sham operated (control), ovariectomized-vehicle and ovariectomized treated animals receiving fennel essential oil (FEO 500, 750, 1000 mg kg<sup>-1</sup>) or estradiol valerate (5 mg kg<sup>-1</sup>) for 30 days. The findings assessed on the basis of bone mineral density and uterine weight showed that the fennel essential oil has a preventive effect on development of osteoporosis in ovariectomized rats. This protective effect of FEO on early post-ovariectomy bone loss was dose dependent and at the dose of 1000 mg kg<sup>-1</sup> it was even more than estradiol (BMD of 0.082±0.008 g cm<sup>-2</sup>, p<0.05) but more toxic than other doses. Trans-anethole, probably has an important role in these pharmacological effects.
... Fennel (Foeniculum vulgare L.), a well-known Mediterranean aromatic herb from the family of Apiaceae, is rich in phytoestrogens such as lignans and has wide spectrum usage in herbal medicine. This medicinal plant has been used to reduce pain in menstruation (dysmenorrhea), to regulate menstruation, to reduce menopausal aches and symptoms, to reduce gastrointestinal pains [10][11][12], to treat osteoporosis [13] and to treat hirsutism [14]. Fennel compounds have been analysed and their effective fractions defined [12] but there is the possibility of different percentage composition of their fractions in different regions. ...
... Phenolic and volatile aroma compounds such as trans-anethole, limonene, and fenchone have been reported as the most important constituents of this herb. As mentioned above, treatment effects of fennel on dysmenorrhea, gastrointestinal pain, menstrual regulation, menopausal signs, hirsutism, and osteoporosis may be attributed to its steroidogenic components such as lignans [10][11][12][13][14]. Other notable effects of fennel include enhanced libido, testicular growth, increased mammary glands, induction of folliculogenesis, and increased numbers of growing ovarian follicles [12,27,28]. ...
Evaluation of protective effect of fennel on mouse ovary against the destructive effects of cyclophosphamide (CP) was the aim of this study. Adult female NMARI mice were randomly divided into six groups (n = 8): (A) negative control, (B) CP200 mg/kg, (C) fennel 400 mg/kg/day, (E, F, and D) that received fennel 200, 400 and 100 mg/kg/day respectively + CP200 mg/kg. Their ovary weight, volume, and diameter (WVD) were measured. Five micron sections were stained using the H&E method. The serum levels of oestrogen and progesterone were measured using ELISA kit. The results showed that WVD significantly reduced in the CP-treated groups in comparison with the A and C, but WVD increased after treatment of the mice with fennel extract, in comparison with B group. A significant decrease of serum in terms of oestrogen and progesterone levels among CP-treated groups in comparison with the A group was observed. In the CP-treated groups a reduction in the number of different ovarian follicles in comparison with the A and C groups was observed. However, in the treated animals with fennel extract, these parameters significantly increased in comparison with the B group. Finally, it is concluded that fennel can protect ovary from cyclophosphamide side effects.
... One more compound taken into consideration in one study is fennel essential oil (FEO). The major components of fennel essential oil (FEO) are trans-anethole, fenchone, and limonene [19] . ...
... The major component of FEO is trans-anethole that has estrogenic activity. Hence it seems that tarns-anethole has the potential to interact with estrogen receptors present in the body [19] . ...
Cisplatin is an effective anticancer drug but it has many side effects at a dose which shows therapeutic response. The main dose limiting side effect is nephrotoxicity. Cisplatin mediated nephrotoxicity is remarkably documented by reactive oxygen species generation and decreased levels of antioxidant mechanisms in the body. A single dose of cisplatin (5mg/kg, i.p) caused a marked renal damage, characterized by a significant increase in serum creatinine, blood urea nitrogen (BUN) and relative weight of kidney with higher kidney malondialdehyde (MDA), reactive oxygen species (ROS), levels and lowered tissue nitrite, SOD, CAT, GSH levels compared to normal control. Different antioxidants have been proven to have nephro protectant action but in some cases the protective effect of these antioxidants is found to be altered in the presence of some hormones in the males and females. Hence the reasons for the change in the nephrotoxicity to be gender related are further discussed in the article.
... Variations in the relationship between SF and BMD across different studies may be attributed to factors such as, study design, age, sex, and site of BMD measurement. Nevertheless, coexistence of disease conditions especially chronic lung and renal diseases, diabetes, MetS, and obesity which are prevalent in the general population as well as in elderly patients can confound the results (12,(22)(23)(24). These conditions are usually associated with inflammatory process and thus, may impress on both SF and BMD sera (6,25). ...
Background
Iron overload influences negatively on bone mineral density (BMD) but the results of studies regarding serum ferritin (SF) and BMD are conflicting.This study aimed to determine the association of SF and BMD in the elderly.
Methods
All participants of the Amirkola cohort selected between 2011-2012, aged > 60 years were classified as high or normal (<200ng/ml) SF. BMD at femoral neck and lumbar spine was determined by dual energy x-ray absorptiometry (DXA) and the results were expressed as BMD g/cm2 and BMDT-score. Multiple logistic regression analysis with calculation of odds ratio (OR) and 95% confidence interval was used to estimate the association of low BMD (LBMD) defined as BMD T-score < -1 with SF.
Results
1089 subjects (women, 44.7%) were studied. High SF was observed in 366 (33.6%) and LBMD in 874 (80.2%) subjects. The two groups of SF were similar regarding biochemical parameters and demographic characteristics except MetS, overweight /obesity and diabetes which were more prevalent in high SFgroup. BMD g/cm2 at both measurement sites was significantly higher (P=0.001 for both) and the prevalence of LBMD was significantly lower (74.1% vs 83.1%, P=0.001) in high SF group by OR= 0.60 (0.44-0.81). After adjustment for all biochemical and demographic variables, the association remained significant by adjusted OR= 0. 68 (0.49-0.94).
Conclusions
These findings show a negative association between high SF and LBMD indicating a beneficial effect of high SF in the elderly. Regarding detrimental effect of iron overload on bone mass, these findings require further studies.
... This protective effect on early post-ovariectomy bone loss was dose dependent and at the dose of 1000 mg/kg, it was even more than estradiol (BMD of 0.082±0.008 g cm-2, p<0.05) [101]. The clinically efficacy of fennel extract was compared with echinophora-platyloba in the primary dysmenorrhea. ...
Medicinal plants have been widely used to enhance or regulate fertility in females. Several medicinal plants stimulated normal pituitary reponse of gonadotropin-releasing hormone, improved normal pulsatile secretion of FSH and LH, induced ovulation, enhanced secretion of steroid hormones, possessed estrogenic and progesteronic effects, and directly regulate ovarian function, at least in part by inducing the secretion of cytokine. Also many herbal therapeutics controlled birth. The current review will highlight the medicinal plants used to enhance fertility and to control birth in females, which confirmed experimentally and clinically.
... This protective effect on early post-ovariectomy bone loss was dose dependent and at the dose of 1000 mg/kg, it was even more than estradiol of 0.082±0.008 g cm 2 , P<0.05) (79) . ...
As a result of accumulated experience from the past generations, today, all the world's cultures have an extensive knowledge of herbal medicine. Plants are a valuable source of a wide range of secondary metabolites, which are used as pharmaceuticals, agrochemicals, flavours, fragrances, colours, biopesticides and food additives. This study was designed to highlight the chemical constituents and pharmacological effects of Foeniculum vulgare.
... We could not find any previous study that assessed the effects of fennel on vaginal atrophy. However, because an active biological compound in fennel is phytoestrogen [17], we referred to studies that assessed the phytoestrogen effects on vaginal atrophy. Phytoestrogens are plant compounds with estrogen-like properties. ...
... Fennel is another type of phytoestrogenic herbs. Fennel essence obtained from distillation of its fruit by means of water steam is pale yellow and aromatic liquid which gradually turns brown (20)(21)(22). Fennel chemicals include: 10% fat, slightly sweet and mucilage and about 4% essence. Fennel oil composes of 4% palmitic acid, 22% oleic acid, 14% linoleic acid and 60% petroselinic acid (22). ...
One of the most important families of Iranian flora is Apiaceae (Umbelliferae). Most of the species of this family are aromatic plants and rich in essential oils with diverse structures. In the present review, the essential oil composition of 63 genera comprising 141 Apiaceae (66.4% native 33.6% endemic) are summarized.
The present study was undertaken to investigate the effects of methanolic extract of Foeniculum vulgare fruits (family: umbelifereae), popularly known as fennel, on depression using force swim test in rats, potentiation of norepinephrine toxicity in mice and haloperidol induce catalepsy in mice. The extract of F. vulgare (250 and 500 mg/kg) was administered orally to rats used in FST and 500mg/kg was administered in HIC and same dose administered in NE toxicity in mice. The dose of 250mg/kg and 500mg/kg of extract significantly (p<0.001) reduced the immobility times in rats but dose of 500 mg/kg showed more potent effect than imipramine (30mg/kg). So this dose was used in HIC and NE toxicity in mice. But in NE toxicity model it was observed that MEFV is not good adrenergic component. A significant (p<0.001) reduction in the duration of catalepsy was observed in the MEFV treated group and Fluoxetine group as compared to the haloperidol treated group. In HIC, mice were sacrificed on the seventh day and TBARS, glutathione, nitrite activities were estimated. Monoamine oxidase inhibiting effect and anti-oxidant effect of Foeniculum vulgare may be contributing favorably to the antidepressant-like activity. Thus, it is concluded that Foeniculum vulgare extract may possess an antidepressantlike effect.
Estrogenic responses have not only been associated with endocrine function, but also with cognitive function. Several studies have indicated that estrogen replacement therapy has favourable effects on cognition, and may have potential in the prevention and treatment of Alzheimer's disease. Thus, ligands for the estrogen receptor, that have a better efficacy and adverse-effect profile than drugs currently available, require investigation. This study was undertaken to investigate the potential estrogenic activity of a number of essential oil constituents. Initially, estrogenic activity was determined by a sensitive and specific bioassay using recombinant yeast cells expressing the human estrogen receptor. At high concentrations, estrogenic activity was detected for citral (geranial and neral), geraniol, nerol and trans-anethole, while eugenol showed anti-estrogenic activity. Molecular graphics studies were undertaken to identify the possible mechanisms for the interaction of geranial, neral, geraniol, nerol and eugenol with the ligand-binding domain of the estrogen alpha-receptor, using the computer program HyperChem. Citral, geraniol, nerol and eugenol were also able to displace [(3)H]17beta-estradiol from isolated alpha- and beta-human estrogen receptors, but none of these compounds showed estrogenic or anti-estrogenic activity in the estrogen-responsive human cell line Ishikawa Var I at levels below their cytotoxic concentrations, and none showed activity in a yeast screen for androgenic and anti-androgenic activity. The potential in-vivo estrogenic effects of citral and geraniol were examined in ovariectomized mice, but neither compound showed any ability to stimulate the characteristic estrogenic responses of uterine hypertrophy or acute increase in uterine vascular permeability. These results show that very high concentrations of some commonly used essential oil constituents appear to have the potential to interact with estrogen receptors, although the biological significance of this is uncertain.
The laboratory rat is the most common animal used in in vivo skeletal research. There are a variety of conditions and states that result in bone loss (osteopenia) in the rat, replicating many known conditions in the human. As such, many of these osteopenic states and conditions provide convenient models to study the mechanisms of osteopenia as well as to explore therapeutic agents to delay, prevent, or reverse the osteopenia. Some of the more common conditions that result in skeletal osteopenia include endocrine deficiencies, endocrine excesses, reproductive cycles, calcium deficiency, vitamin deficiencies, skeletal underloading, and aging. Various caveats in the use of the rat skeleton as a model for the human are presented. (The J Histotechnol 20:209, 1997)
Essential oil of fennel cultivated in Iran was obtained by hydrodistillation and supercritical (CO2) extraction (SFE) methods. The oils were analysed by capillary gas chromatography using flame ionization and mass spectrometric detection. The compounds were identified according to their retention indices and mass spectra (EI, 70 eV). The effects of different parameters, such as pressure, temperature, modifier volume and extraction time, on the supercritical fluid extraction of fennel oil were investigated. The results showed that, under pressure of 350 atm, temperature 55 °C, methanol 5% and dynamic extraction time of 45 min, extraction was more selective for the extraction of (E)-anethol. Sixteen compounds were identified in the hydrodistilled oil. However, by using supercritical carbon dioxide in optimum conditions, only nine components represented more than 99% of the oil. The results showed that, in Iranian fennel oil, (E)-anethol is a major component. Copyright © 2002 John Wiley & Sons, Ltd.
Following the oral administration of acetone extract of Foeniculum vulgare (fennel) seeds for 15 days is male rats, total protein concentration was found to be significantly decreased in testes and vas deferens and increased in seminal vesicles and prostate gland. There was a decrease in activities of acid and alkaline phosphatase in all these regions, except that alkaline phosphatase was unchanged in vasa. In female rats, oral administration of the extract for 10 days led to vaginal cornification and oestrus cycle. While moderate doses caused increase in weight of mammary glands, higher doses increased the weight of oviduct, endometrium, myometrium, cervix and vagina also. The results confirm the oestrogenic activity of the seed extract.
Conventional hormone replacement therapy preserves bone mass predominantly by reducing bone turnover but does not exert significant anabolic skeletal effects. In contrast, high doses of estrogen have been shown to increase bone formation in animals and we have recently reported high bone mineral density values in women treated long-term with estradiol implant therapy. The aim of this study was to investigate the mechanisms by which high doses of estrogen may increase bone mass in postmenopausal women. Iliac crest biopsies were obtained from 12 women who had received long-term treatment with estradiol implants (at least 14 years), on demand, following hysterectomy and bilateral salpingo-oophorectomy. Indices of bone turnover, remodeling balance and cancellous bone structure were assessed by image analysis and compared with those of premenopausal women. Mean wall width was significantly higher in women treated with estradiol therapy than in premenopausal women (44. 8 +/- 4.8 vs 38.8 +/- 2.8 mm; mean +/- SD; p = 0.001) and eroded cavity area was significantly lower in the implant-treated women (3612 +/- 956 vs 5418 +/- 1404 mm(2); p = 0.001). Bone formation rate at tissue level and activation frequency were lower in the women treated with implants, although the differences were not statistically significant. Indices of cancellous bone structure were generally similar between the two groups. These results provide the first direct evidence that high-dose estrogen therapy produces anabolic skeletal effects in postmenopausal women and indicate that these are achieved by stimulation of osteoblastic activity.
To combine the results of randomized controlled trials to provide overall estimates of the effect of estrogen treatment on fracture rates and measures of bone mass.
Articles on estrogen treatment for osteoporosis published between 1977 and 1995 were identified.
Studies selected were randomized controlled trials of the efficacy of estrogens in preventing loss of bone mass or fractures in postmenopausal women.
Data extraction and quality assessment were performed in duplicate, with assistance of a manual. Raters were blinded as to authors and their affiliations and the publication details. With estimates of bone mass, the treatment effect size was defined as the difference in the mean annual change in bone mass between the treatment and control groups divided by the pooled standard deviation for change. In the case of fractures, efficacy was measured as the reduction in the numbers of individuals experiencing new fractures with treatment. Effect sizes were pooled using the random effects model.
Thirty-seven studies met the criteria for inclusion in the systematic review. Only one small secondary prevention trial contained evaluable data on vertebral fractures. This study found a fracture relative risk of 0.63 (95% confidence interval, CI 0.28-1.43) with estrogen treatment. There was more information on the effects of treatment on bone mass. Overall effect sizes ranged between 0.5 and 2.5 standard deviation (SD) units for change. A dose-response relationship was apparent but high doses of estrogens were not associated with effect sizes greater than those observed with recommended doses. There was no significant difference in efficacy between transdermal and oral administration of estrogens. Pooling of paired data from secondary prevention studies indicated that treatment effect sizes were smaller at the hip (0.92, 95% CI 0.3-1.5 SD units) than at the spine (2.1, 95% CI 0.9-3.3 SD units). No significant effects of co-intervention with calcium, progestogens or androgens were seen, although an additive effect of higher doses of calcium could not be ruled out.
Clear-cut effects of estrogens in attenuating the postmenopausal decline in estimated bone mass were apparent in this literature. However, the trials were short-term and provide inadequate evidence on the effects of treatment on fracture risk.
Menopausal hormone decline contributes significantly to the risk of osteoporosis. Therapies for treating osteoporosis, such as hormone replacement therapy (estrogen or combination estrogen-progestins), inhibit bone resorption. Both animal and human studies demonstrate phytoestrogenic soy isoflavones favorably impact bone health. The exact mechanism is still unclear. Additional research is needed to determine if isoflavones are an effective alternative to hormone replacement therapy for the prevention and treatment of osteoporosis. This paper reviews in vitro, animal, and human studies involving isoflavones and bone health.
To compare the effect of Foeniculum vulgare variety dulce (Sweet Fennel) vs. mefenamic acid for the treatment of primary dysmenorrhea.
A cohort of seventy women, 15-24 years old from a local university and high-school, who complained of dysmenorrhea were enrolled in this study. Ten cases were excluded due to evidence of secondary dysmenorrhea. The remaining 60 patients were graded mild, moderate and severe on the basis of a verbal multidimensional scoring system. Thirty patients with mild dysmenorrhea were also excluded from the study. Each of the 30 cases with moderate to severe dysmenorrhea was evaluated for three cycles. In the first cycle no medication was given (control cycle), in the second cycle the cases were treated by mefenamic acid (250 mg q6h orally) and in the third cycle, essence of Fennel's fruit with 2% concentration (25 drops q4h orally), was prescribed at the beginning of the cycle. These cycles were compared day by day for the effect, potency, time of initiation of action and also complications associated with each treatment modality, by using a self-scoring system. Intensity of pain was reported by using a 10-point linear analog technique. Statistical analyses were performed by the independent sample t-test, paired t-test and repeated measurement analysis method.
In the study group the mean age of menarche was 12.5+/-1.3 years, the mean duration of menstruation was 6.6+/-1.4 days with the mean cycle days of 27+/-3. The findings observed during menses were as follows: headache in 26.7%, nausea in 63.3%, vomiting in 23.3%, diarrhea in 33.3%, fatigue in 93.3% and leaving the daily tasks undone was reported in 86.9% of the cases. Both of the drugs effectively relieved menstrual pain as compared with the control cycles (P<0.001). The mean duration of initiation of action was 67.5+/-46.06 min for mefenamic acid and 75+/-48.9 min for fennel. The difference was not statistically significant (P=0.57). Mefenamic acid had a more potent effect than fennel on the second and third menstrual days (P<0.05), however, the difference on the other days was not significant. No complication was reported in mefenamic acid treated cycles, but five cases (16.6%) withdrew from the study due to fennel's odor and one case (3.11%) reported a mild increase in the amount of her menstrual flow.
The essence of fennel can be used as a safe and effective herbal drug for primary dysmenorrhea, however, it may have a lower potency than mefenamic acid in the dosages used for this study.
Idiopathic hirsutism is defined as the occurrence of excessive male pattern hair growth in women who have a normal ovulatory menstrual cycle and normal levels of serum androgens. It may be a disorder of peripheral androgen metabolism. In this study we evaluated the clinical response of idiopathic hirsutism to topical Fennel extract. Fennel, Foeniculum vulgare, is a plant, which has been used as an estrogenic agent. The ethanolic extract of Fennel was obtained by using a soxhlete apparatus. In a double blind study, 38 patients were treated with creams containing 1%, 2% of Fennel extract and placebo. Hair diameter was measured and rate of growth was considered. The efficacy of treatment with the cream containing 2% Fennel is better than the cream containing 1% Fennel and these two were more potent than placebo. The mean values of hair diameter reduction was 7.8%, 18.3% and -0.5% for patients receiving the creams containing 1%, 2% and 0% (placebo) respectively.
To observe the effect of phytoestrogen (PE) in preventing and treating osteoporosis in ovariectomized rats.
Forty-five Wistar female rats, 3 months old, were randomly divided into the sham-operated group, the model group, low dose and high dose PE groups, and the positive control group, 9 in each group. All rats, except that those in the sham operated group were simutaneously operated, were ovariectomized. The medication started from the 31st days after operation by daily given saline per os to the sham-operated group and the model group, PE per os to the PE groups, and estradiol by intramuscular injection to the positive control group. The animals were sacrificed 90 days later, their sera were collected for determination of biochemical parameters, their right femoral bone was taken to detect the bone mineral density (BMD), left femoral bone to examine pathology of bone trabecula, and whole uterus was weighed to calculate the uterine index.
PE could increase the BMD level, serum estradiol and inorganic phosphorus content, and uterine index, lower serum BGP, tartrate-resistant acid phosphatase (TRAP), alkaline phosphatuse (AKP) and interleukin-6 levels. Pathological examination showed that in the model group, the cortex of bone thinned, bone trabecula thinned also, with poor integrity, distorted, broken and decreased in size, while in the PE groups, the above-mentioned changes were significantly alleviated.
PE is effective in preventing and treating osteoporosis in ovariectomized rats.