In utero and postnatal exposure to Foeniculum vulgare and Linum usitatissimum seed extracts: modifications of key enzymes involved in epigenetic regulation and estrogen receptors expression in the offspring's ovaries of NMRI mice.

BACKGROUND: Early-life exposure to exogenous estrogens such as phytoestrogens (plant-derived estrogens) could affect later health through epigenetic modifications. Foeniculum vulgare (fennel) and Linum usitatissimum (flax) are two common medicinal plants with high phytoestrogen content. Considering the developmental epigenetic programming effect of phytoestrogens, the main goal of the present study was to evaluate the perinatal exposure with life-long exposure to hydroalcoholic extracts of both plants on offspring's ovarian epigenetic changes and estrogen receptors (ESRs) expression level as signaling cascades triggers of phytoestrogens. METHODS: Pregnant mice were randomly divided into control (CTL) that received no treatment and extract-treated groups that received 500 mg/kg/day of fennel (FV) and flaxseed (FX) alone or in combination (FV + FX) during gestation and lactation. At weaning, female offspring exposed to extracts prenatally remained on the maternal-doses diets until puberty. Then, the ovaries were collected for morphometric studies and quantitative real-time PCR analysis. RESULTS: A reduction in mRNA transcripts of the epigenetic modifying enzymes DNMTs and HDACs as well as estrogen receptors was observed in the FV and FX groups compared to the CTL group. Interestingly, an increase in ESRα/ESRß ratio along with HDAC2 overexpression was observed in the FV + FX group. CONCLUSION: Our findings clearly show a positive relationship between pre and postnatal exposure to fennel and flaxseed extracts, ovarian epigenetic changes, and estrogen receptors expression, which may affect the estrogen signaling pathway. However, due to the high phytoestrogen contents of these extracts, the use of these plants in humans requires more detailed investigations.

"Natural" relief of pregnancy-related symptoms and neonatal outcomes: above all do no harm.

ETHNOPHARMACOLOGICAL RELEVANCE: In the South of Italy the use of herbal remedies to alleviate pregnancy-related symptoms is very common. OBJECTIVES: To investigate the proportion, prevalence of use, attitude and knowledge base in a sample of Italian pregnant women in the South of Italy. To explore the possible influence and risks of herbal consumption on pregnancy and neonatal outcomes. METHODS: A retrospective observational study was conducted during the study period November 2010-September 2013. Six hundred and thirty expectant mothers were interviewed within three days after childbirth in a public Hospital in the South of Italy. RESULTS: Due to a lack of data, a total of six hundred interviews were considered. Four hundred and eighty six women (81%) reported to have constantly used at least one herbal product throughout the pregnancy period. The study enrolled mostly women between 31 and 40 years of age, with a middle-high level of education, married and employed. The most commonly used herbal products, taken by oral route and for the entire period of pregnancy, were chamomile, fennel, propolis, cranberry, lemon balm, ginger, valerian and mallow. The most relevant source of information for the majority of participants was the doctor (95%), and most of the women (72%) informed their doctors about their use of herbal remedies. CONCLUSIONS: The regular chamomile consumption resulted in a higher risk of pre-term delivery, lower birth weight and lower length of the newborn. Also a regular use of fennel resulted in a shorter gestational age. Finally, ginger intake resulted in a shorter gestational age and in a smaller circumference of the newborn's skull.

Mugwort-fennel-allergy-syndrome associated with sensitization to an allergen homologous to Api g 5.

BACKGROUND: The cross-reactive allergen responsible for the so called "mugwort-celery-spice-syndrome", a pollen-food allergy that occurs in a minority of mugwort pollen-allergic patients, is still undefined. OBJECTIVE: To identify the allergen responsible for the cross-reactivity between mugwort pollen and plant-derived foods. METHODS: The serum from one index patient with both fennel and mugwort pollen allergy was used to identify IgE-reactive allergens by direct ELISA and Immunoblot analysis. Cross-reactivity between mugwort pollen and fennel was checked by cross-inhibition experiments. Fennel and mugwort allergens selected on the basis of IgE reactivity and inhibition tests were excised from SDS-PAGE gels and microsequenced. The amino acid sequences obtained were used to screen the NCBI database using the protein BLAST software. RESULTS: On ELISA inhibition experiments, serum absorption with fennel extract completely inhibited the IgE response to mugwort. On immmunoblot analysis periodate treatment caused the disappearance of all bands of IgE reactivity except one at about 60 kDa. The 60 kDa bands from both mugwort and fennel PAGE-SDS gels revealed the presence of distinct proteins. The N-terminal amino acid sequencing gave the same major amino acid sequence corresponding to an Api g 5-like allergen. The MS/MS spectra were analyzed and a provided evidence of a fennel-specific protein with sequence similarity to phosphoglyceromutase from Apium graveolens. CONCLUSION: A 60 kDa allergen, highly homologous to Api g 5, was recognized in fennel by patient's IgE. Inhibition experiments showed a high degree of cross-reactivity between this fennel allergen and the homologous mugwort pollen allergen. This allergen might be responsible for the mugwort-celery-spice syndrome.

Herbal supplements in pregnancy: unexpected results from a multicentre study.

STUDY QUESTION: How common is the use of herbal supplements during pregnancy and does it adversely affect the pregnancy outcome? SUMMARY ANSWER: The use of herbal products during pregnancy is very common and daily almond oil spreading is associated with preterm birth (PTB). WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Herbal drugs are often promoted as 'natural' and 'safe' and such claims attract pregnant women. More than a quarter of Italian pregnant women consume herbs every day for at least 3 months during pregnancy. We raise an alert over the habit of daily almond oil spreading since it seems to be associated with PTB. DESIGN: A multicenter retrospective cohort study performed over a 15-month period. PARTICIPANTS AND SETTING: Seven hundred women interviewed within 3 days of childbirth, in three public hospitals in northern Italy. MAIN RESULTS AND ROLE OF CHANCE: One hundred and eighty-nine women were considered 'regular users', since they consumed herbs every day, for at least 3 months. Almond oil, chamomile and fennel were the most commonly used herbs. Both length of gestation and birthweight were affected by herb consumption. Almond oil users showed more pre-term birth (29 of 189) than non-users (51 of 511). After adjusting for multiple pregnancies, smoking, advanced age and drug intake, almond oil users maintained an increased risk to give birth <37th week (odds ratio = 2.09, 95% confidence interval: 1.08-4.08). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: The association between daily spreading of almond oil and PTB only raises a hypothesis that requires confirmation in larger trials devoted to this topic. The relatively small sample size did not allow the investigation of other adverse pregnancy outcomes in herb users. GENERALIZABILITY TO OTHER POPULATIONS: The population under investigation did not significantly differ from the general population attending the same hospitals. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest exists. The study has been supported by a public grant from the University of Modena and Reggio Emilia. TRIAL REGISTRATION NUMBER: None.

Epileptic seizure induced by fennel essential oil.

An epileptic seizure is reported in a 38-year-old woman, known to be an epileptic patient. Although she was under antiepileptic treatment and had well-controlled epilepsy, she developed a typical generalised tonic-clonic seizure and remained unconscious for 45 minutes following ingestion of a number of cakes containing an unknown quantity of fennel essential oil. Involuntary diarrhoea accompanied her epileptic seizure. This reported case recalls the fact that fennel essential oil can induce seizures and that this oil should probably be avoided by patients with epilepsy. Labelling of products with fennel essential oil should refer to the risk of seizures, particularly for patients with epilepsy. An awareness programme should involve all stakeholders affected by this issue.

A striking and frequent cause of premature thelarche in children: Foeniculum vulgare.

Isolated premature thelarche is a common disorder characterized by breast development, usually younger than 2 years, with no other signs of puberty. Although it is usually associated with adrenal or ovarian disorders, hypothyroidism, and use of exogenous hormones or drugs, it may also be associated with long-term use of herbal medicine. Thus, long-term use of preparations such as Foeniculum vulgare, which is used to eliminate gas and regulate intestinal function in children, may cause premature thelarche, and thus, the use of such preparations should be limited.

Severe iron deficiency anemia and gastrointestinal dysfunction associated with ingestion of pan masala.

A severe iron deficiency state and problematic upper gastrointestinal irritation developed in an adult female who ingested pan masala that included fennel seed and betel nut. This illness illustrates the potential complexity of clinical presentation when mixtures of herbal contents are ingested. Clinical history-taking should routinely consider the potential importance of traditional customs.