Blue Cohosh Research Articles

Neuroactivity screening of botanical extracts using microelectrode array (MEA) recordings

Toxicity testing of botanicals is challenging because of their chemical complexity and variability. Since botanicals may affect many different modes of action involved in neuronal function, we used microelectrode array (MEA) recordings of primary rat cortical cultures to screen 16 different botanical extracts for their effects on cell viability and neuronal network function in vitro. Our results demonstrate that extract materials (50 μg/mL) derived from goldenseal, milk thistle, tripterygium, and yohimbe decrease mitochondrial activity following 7 days exposure, indicative of cytotoxicity. Importantly, most botanical extracts alter neuronal network function following acute exposure. Extract materials (50 μg/mL) derived from aristolochia, ephedra, green tea, milk thistle, tripterygium, and usnea inhibit neuronal activity. Extracts of kava, kratom and yohimbe are particularly potent and induce a profound inhibition of neuronal activity at the low dose of 5 μg/mL. Extracts of blue cohosh, goldenseal and oleander cause intensification of the bursts. Aconite extract (5 μg/mL) evokes a clear hyperexcitation with a marked increase in the number of spikes and (network) bursts. The distinct activity patterns suggest that botanical extracts have diverse modes of action. Our combined data also highlight the applicability of MEA recordings for hazard identification and potency ranking of botanicals.

Non-targeted chemical analysis of consumer botanical products labeled as blue cohosh (Caulophyllum thalictroides), goldenseal (Hydrastis canadensis), or yohimbe bark (Pausinystalia yohimbe) by NMR and MS.

Consumers have unprecedented access to botanical dietary supplements through online retailers, making it difficult to ensure product quality and authenticity. Therefore, methods to survey and compare chemical compositions across botanical products are needed. Nuclear magnetic resonance (NMR) spectroscopy and non-targeted mass spectrometry (MS) were used to chemically analyze commercial products labeled as containing one of three botanicals: blue cohosh, goldenseal, and yohimbe bark. Aqueous and organic phase extracts were prepared and analyzed in tandem with NMR followed by MS. We processed the non-targeted data using multivariate statistics to analyze the compositional similarity across extracts. In each case, there were several product outliers that were identified using principal component analysis (PCA). Evaluation of select known constituents proved useful to contextualize PCA subgroups, which in some cases supported or refuted product authenticity. The NMR and MS data reached similar conclusions independently but were also complementary.

Isolation and Characterization of the Genes Involved in the Berberine Synthesis Pathway in Asian Blue Cohosh, Caulophyllum robustum

Caulophyllum robustum, commonly named Asian blue cohosh, is a perennial herb in the family Berberidaceae. It has traditionally been used for folk medicine in China. We isolated berberine from the leaves, stem, roots, and fruits of C. robustum, and this is the first report on berberine in this species. Transcriptome analysis was conducted for the characterization of berberine biosynthesis genes in C. robustum, in which, all the genes for berberine biosynthesis were identified. From 40,094 transcripts, using gene ontology (GO) analysis, 26,750 transcripts were assigned their functions in the categories of biological process, molecular function, and cellular component. In the analysis of genes expressed in different tissues, the numbers of genes in the categories of intrinsic component of membrane and transferase activity were up-regulated in leaves versus stem. The berberine synthesis genes in C. robustum were characterized by phylogenetic analysis with corresponding genes from other berberine-producing species. The co-existence of genes from different plant families in the deepest branch subclade implies that the differentiation of berberine synthesis genes occurred early in the evolution of berberine-producing plants. Furthermore, the copy number increment of the berberine synthesis genes was detected at the species level.

Safe as Lightning by Scudder H. Parker

Reviewed by: Safe as Lightning by Scudder H. Parker Patricia Carragon (bio) safe as lightning Scudder H. Parker Rootstock Publishing https://www.rootstockpublishing.com/rootstock-books/safe-as-lightning 134 pages; Print, $15.95 For someone who lived most of her life trapped in the hustle and bustle of filthy streets and subways, surrounded by noise and air pollution, and devalued by toxic work conditions that added to her generational karma, reading Scudder H. Parker's Safe as Lightning would have been daunting. However, it wasn't. In fact, it was spiritually enlightening. Having been through the COVID-19 lockdown for most of 2020, I shifted from political anger to being grounded—more open to oneness with nature and humanity, learning to forgive myself and others, putting the past on the shelf, and experiencing life in a haiku moment. Parker's approach is no-frills. His poetry has a forgotten wholesomeness seen in children's books or in movies like It's a Wonderful Life. His poems are honest, untainted by sentimentality. His simplicity and humility tell stories [End Page 145] of everyday life without urban drama: his boyhood to manhood, the family farm, living in Vermont, his marriage and family, and so forth. We get to laugh at the author's dilemma of feeding the cats. We learn how unruly broccoli can be and that he has an affection for toads. He introduces us to his grandson, his mother's art, and more. In his introductory poem, "The Poem of the World," Parker brings our senses to hear, see, and feel nature: a doe tapping its hoof to break the ice, purplish rust on forsythia leaves, red and blue potatoes drying in the sun, the lovemaking tickles of shared laughter, the singing of ocean pebbles, and a morning chorus of birds. The wanting to become part of the natural world. Each stanza is as exquisite as the first. The one that resonates the most is: The poem of the world wants me to wakein my own body; it is astonished I might letthese bones grow brittle. The author realizes that he is trapped in a body destined to age, but his environment leaves him in awe. He learns to live in the present, not to worry about the future. His call to serving the public and for Christ Conscientious humanizes Jesus Christ in "Early Memories of Jesus." He depicts Christ as his secret friend, rather than the iconic Savior on the Cross, in the Bible, or in a sermon: Though I never spoke his name,he was the friend who daydreamed with me … He could find wild gingerunder leaves bleached and frailed by winter;blue cohosh uncurling fingersthe color of evening in a maple woods.We found and ate wild onions, green flags,red bulbs flecked with loam,so spring would infect our breath. He goes on to say that Christ taught him how to enjoy the land and its riches, and share their echoes across the valley. The Crucifixion never entered their conversations. It was best left in the past. Parker believes that Christ wasn't [End Page 146] overcome by charity after leaving home, but finally reached God through sacrifice. Years pass, and their friendship endures. Christ has a small place on the edge of town, and they pick wild onions for soup, watch the night sky lighten: I asked if he had heard from God.He said he hadn'tand still missed him,but he understoodhow easy it is to get preoccupied. As we talked, the moon—the somewhat predictabletemporary moon—that tugstwice every day at our bodiesrose like a fragile eggin the denim sky. As an adult, Sutter retains his intimate friendship with the human Christ. Christ hasn't heard from God, possibly because God might be preoccupied. There is no malice or rancor, only a compassionate understanding as they watch the "fragile egg" moon rise in the "denim sky." The farm metaphors work, bring humility and acceptance to close the final stanza. In "Humility," Parker opens his wounds. It takes twenty-five years for him to learn from his land's rot within his...

Current research opportunities for potential phytotherapeutic agents for the treatment of pathologies of the female reproductive system

Introduction and aim. Herbal medicine is prescribed for various disorders of the menstrual cycle (uterine bleeding, dysmenorrhea), for the treatment of premenstrual and climacteric syndromes, inflammatory diseases of the genital organs, mastopathy and mastalgia and other pathological conditions. The aim of the study is to analysis and generalization of data from professional literature and own experience in the treatment of patients with pathologies of the female reproductive system by phytotherapeutic methods, taking into account the influence of medicinal plants on various links in the pathogenesis of the disease, as well as making recommendations for improvement and prospects for the use of phytotherapy in the treatment of this pathology. Material and methods. To make an analysis of literary sources of domestic and foreign authors about usage of medicinal plants for the treatment of pathologies of the female reproductive system. Analysis of the literature. In the treatment of primary (spasmodic) dysmenorrhea, herbal remedies with an antispasmodic, analgesic, hormone-mimetic effects are prescribed. It can be Chamomile (Matricaria chamomilla L.), Achillea millefolium, commonly known as yarrow, Viburnum, Shepherd’s purse (Capsella bursa-pastoris), Greater celandine, Atropa belladonna, Hyoscyamus niger, commonly known as henbane, black henbane, or stinking nightshade and Abraham’s tree. Many plants have bactericidal activity, and this property is used in the treatment of inflammatory diseases of the mucous membranes and skin. Such properties are possessed by flowers of Chamomile (Matricaria chamomilla L.), Calendula officinalis, infusion of Medicinal sage (Salvia officinalis L.). For the treatment of functional hyperprolactinemia phytopreparations are also successfully used. It is known that the medicinal plant Vitex agnus castus has dopaminergic properties, selectively blocking prolactin synthesis, and reduces follicle stimulating hormone levels. Strychnos ignatia, Caulophyllum thalictroides, European cyclamen, Lilium tigrinum, Iris versicolor provide a complex effect on the female body, effectively reduces the level of prolactin and the severity of mastalgia, which is confirmed not only by clinical data, but also by mammography data in fibrocystic breast disease. For the treatment of climacteric syndrome, a large number of medicinal plants are used, in particular, the most popular is the Cimicifuga racemose. Conclusion. The effectiveness of phytotherapeutic drugs has been verified by many clinical trials. Modern phytotherapy is becoming more widespread in clinical practice, as an alternative to drug treatment.

Complementary medicines in pregnancy: recommendations and information sources of healthcare professionals in Australia

Background The use of oral complementary and alternative medicines, including herbal supplements, has been increasing in pregnant women worldwide despite limited safety data. The decision of healthcare professionals to recommend these products to pregnant patients is controversial and not well documented. Objective To explore the recommendations and information sources that healthcare professionals use to determine the safety of oral non-prescribed supplements during pregnancy. Setting An Australian metropolitan maternity hospital. Method An electronic survey was distributed to doctors, midwives, pharmacists, dietitians, lactation consultants and physiotherapists. Main outcome measure The nature of recommendations and information sources that healthcare professionals use to determine the safety of oral non-prescribed supplements during pregnancy. Results Responses were received from 54 healthcare professionals. Forty of 54 (74.1%) were concerned about the safety of their patients' supplements, while 35 of 54 (64.8%) felt that they had access to trustworthy safety information. Supplements most commonly recommended as safe to use were ginger (40.7%), probiotics (29.6%) and raspberry leaf (22.2%). Participants specifically requested further safety information for raspberry leaf, evening primrose oil, fish oil, probiotics, ginger, vitamin C, valerian, turmeric, blue cohosh and colloidal silver. Written resources most frequently consulted included MIMS® (61.1%) and 'Google Searches' (29.6%), and healthcare professionals most referred to were pharmacists (74.1%), doctors (22.2%), and naturopaths or herbalists (3.7%). Conclusion The recommendations of maternity heath care professionals and quality of information sources used varied. Further education and access to unbiased safety information is required to empower healthcare professionals to provide informed recommendations to pregnant patients.

Genetic divergence with ongoing gene flow is maintained by the use of different hosts in phytophagous ladybird beetles genus Henosepilachna.

Adaptation to different environments can promote population divergence via natural selection even in the presence of gene flow - a phenomenon that typically occurs during ecological speciation. To elucidate how natural selection promotes and maintains population divergence during speciation, we investigated the population genetic structure, degree of gene flow and heterogeneous genomic divergence in three closely related Japanese phytophagous ladybird beetles: Henosepilachna pustulosa, H.niponica and H.yasutomii. These species act as a generalist, a wild thistle (Cirsium spp.) specialist and a blue cohosh (Caulophyllum robustum) specialist, respectively, and their ranges differ accordingly. The two specialist species widely co-occur but are reproductively isolated solely due to their high specialization to a particular host plant. Genomewide amplified fragment-length polymorphism (AFLP) markers and mitochondrial cytochrome c oxidase subunit I (COI) gene sequences demonstrated obvious genomewide divergence associated with both geographic distance and ecological divergence. However, a hybridization assessment for both AFLP loci and the mitochondrial sequences revealed a certain degree of unidirectional gene flow between the two sympatric specialist species. Principal coordinates analysis (PCoA) based on all of the variable AFLP loci demonstrated that there are genetic similarities between populations from adjacent localities irrespective of the species (i.e. host range). However, a further comparative genome scan identified a few fractions of loci representing approximately 1% of all loci as different host-associated outliers. These results suggest that these three species had a complex origin, which could be obscured by current gene flow, and that ecological divergence can be maintained with only a small fraction of the genome is related to different host use even when there is a certain degree of gene flow between sympatric species pairs.

Herbal therapies in pregnancy: what works?

The aim of this article is two-fold: to report the prevalence of herbal products used by pregnant women and to evaluate the evidence of efficacy and safety of the most popular remedies. Of the 671 articles identified, 15 randomized controlled trials (RCTs) and 16 non-RCTs were eligible. Ginger was the most investigated remedy and it was consistently reported to ameliorate nausea and vomiting in pregnancy. Although raspberry, blue cohosh, castor oil, and evening primrose oil are believed to facilitate labor in traditional medicine, very few scientific data support such indication. Moreover, they have been associated with severe adverse events. Data on the safety of Hypericum perforatum in pregnancy or lactation are reassuring, whereas efficacy was demonstrated only in nonpregnant individuals. There is still insufficient evidence regarding the efficacy and safety of Echinacea, garlic, and cranberry in pregnancy. Epidemiological studies reported a wide range of use of herbal remedies in pregnancy. Too few studies have been devoted to the safety and efficacy of singular herbs. With the exception of ginger, there are no consistent data to support the use of any other herbal supplement during pregnancy. Severe adverse events have been reported using blue cohosh and evening primrose oil.

Toxins in Botanical Dietary Supplements: Blue Cohosh Components Disrupt Cellular Respiration and Mitochondrial Membrane Potential

Certain botanical dietary supplements have been associated with idiosyncratic organ-specific toxicity. Similar toxicological events, caused by drug-induced mitochondrial dysfunction, have forced the withdrawal or U.S. FDA "black box" warnings of major pharmaceuticals. To assess the potential mitochondrial liability of botanical dietary supplements, extracts from 352 authenticated plant samples used in traditional Chinese, Ayurvedic, and Western herbal medicine were evaluated for the ability to disrupt cellular respiration. Blue cohosh (Caulophyllum thalictroides) methanol extract exhibited mitochondriotoxic activity. Used by some U.S. midwives to help induce labor, blue cohosh has been associated with perinatal stroke, acute myocardial infarction, congestive heart failure, multiple organ injury, and neonatal shock. The potential link between mitochondrial disruption and idiosyncratic herbal intoxication prompted further examination. The C. thalictroides methanol extract and three saponins, cauloside A (1), saponin PE (2), and cauloside C (3), exhibited concentration- and time-dependent mitochondriotoxic activities. Upon treatment, cell respiration rate rapidly increased and then dramatically decreased within minutes. Mechanistic studies revealed that C. thalictroides constituents impair mitochondrial function by disrupting membrane integrity. These studies provide a potential etiological link between this mitochondria-sensitive form of cytotoxicity and idiosyncratic organ damage.

Toxins from Botanical Dietary Supplements: Blue Cohosh Components Disrupt Mitochondrial Membrane Integrity and Impair Cellular Respiration

Drug-induced mitochondrial dysfunction has forced the withdrawal of major drugs used to treat diabetes (e.g., troglitazone) and hyperlipidemia (e.g., cerivastatin). Nearly half of the drugs with hepatotoxicity and cardiotoxicity-associated FDA Black Box Warnings interfere with mitochondrial function. While the pharmaceutical industry has begun to evaluate potential mitochondrial liability of new therapeutic agents, the plethora of phytochemicals in botanical dietary supplements (BDS) have not been examined. Extracts from 352 plants used in traditional Chinese, Ayurvedic, and Western Herbal Medicine were evaluated for their potential to disrupt mitochondrial function. Blue cohosh [Caulophyllum thalictroides L. (Berberidaceae)] extract, typically used as an antispasmodic, menstrual flow stimulator, and abortifacient, exhibited mitochondriotoxic activity. This toxicity is particularly noteworthy given a report indicating that approximately 64% of US midwives have used blue cohosh to induce labor. Perinatal stroke, acute myocardial infarction, congestive heart failure, multiple organ injury, and neonatal shock have been associated with blue cohosh tincture/dietary supplements consumption. The potential link between mitochondrial disruption and idiosyncratic herbal intoxication prompted further examination of blue cohosh components on cellular respiration. Three saponins (cauloside A, cauloside C, and saponin PE) exhibited mitochondriotoxic activity in a concentration- and time-dependent manner. Upon treatment, a rapid burst in cellular oxygen consumption was followed by a dramatic decrease in respiration. These constituents impair mitochondrial function by disrupting membrane integrity. Thus, herbal supplements must be carefully evaluated for potential adverse effects on mitochondrial function.

Primary constituents of blue cohosh: quantification in dietary supplements and potential for toxicity

Dietary supplements containing dried roots or extracts of the roots and/or rhizomes of blue cohosh (Caulophyllum thalictroides) are widely available. This botanical has a long history of use by Native Americans and its use continues to the present day. The primary constituents of blue cohosh are its alkaloids and saponins. The structures of the alkaloids magnoflorine, baptifoline, anagyrine, and N-methylcytisine have been known for many years. The last 10 years have seen a great increase in isolation and identification of the large number of saponins present in blue cohosh. Important developments in nuclear magnetic resonance techniques have contributed substantially to the increase in elucidation of the structures of the complex saponins. Several authors have described quantitative methods for both the alkaloids and saponins in blue cohosh. Such methods have made it possible to quantify these constituents in dietary supplements containing this botanical ingredient. Concentrations of both alkaloids and saponins vary substantially in dietary supplements of blue cohosh. The nicotinic alkaloid, N-methylcytisine, a potent toxicant, has been found in all dietary supplements of blue cohosh analyzed. The teratogenic alkaloid anagyrine has been found in some but not all dietary supplements.

Adverse effects of herbal medicines: an overview of systematic reviews

This overview of systematic reviews (SRs) aims to evaluate critically the evidence regarding the adverse effects of herbal medicines (HMs). Five electronic databases were searched to identify all relevant SRs, with 50 SRs of 50 different HMs meeting our inclusion criteria. Most had only minor weaknesses in methods. Serious adverse effects were noted only for four HMs: Herbae pulvis standardisatus, Larrea tridentate, Piper methysticum and Cassia senna. The most severe adverse effects were liver or kidney damage, colon perforation, carcinoma, coma and death. Moderately severe adverse effects were noted for 15 HMs: Pelargonium sidoides, Perna canaliculus, Aloe vera, Mentha piperita, Medicago sativa, Cimicifuga racemosa, Caulophyllum thalictroides, Serenoa repens, Taraxacum officinale, Camellia sinensis, Commifora mukul, Hoodia gordonii, Viscum album, Trifolium pratense and Stevia rebaudiana. Minor adverse effects were noted for 31 HMs: Thymus vulgaris, Lavandula angustifolia Miller, Boswellia serrata, Calendula officinalis, Harpagophytum procumbens, Panax ginseng, Vitex agnus-castus, Crataegus spp., Cinnamomum spp., Petasites hybridus, Agave americana, Hypericum perforatum, Echinacea spp., Silybum marianum, Capsicum spp., Genus phyllanthus, Ginkgo biloba, Valeriana officinalis, Hippocastanaceae, Melissa officinalis, Trigonella foenum-graecum, Lagerstroemia speciosa, Cnicus benedictus, Salvia hispanica, Vaccinium myrtillus, Mentha spicata, Rosmarinus officinalis, Crocus sativus, Gymnema sylvestre, Morinda citrifolia and Curcuma longa. Most of the HMs evaluated in SRs were associated with only moderately severe or minor adverse effects.

Differential acceptance of and survivorship on a non-host plant between two geographically separate populations of the phytophagous ladybird beetle Henosepilachna yasutomii

Phytophagous specialists among insects occasionally accept plants they do not or only rarely utilize under natural conditions. This non-host acceptance could represent an initial stage in host-range evolution. Here, we examined adult acceptance of and larval survivorship on a non-host plant – wild thistle, Cirsium kamtschaticum Ledeb. (Asteraceae) – for two geographically separate populations of the phytophagous ladybird beetle Henosepilachna yasutomii Katakura (Coleoptera: Coccinellidae), which normally utilizes blue cohosh, Caulophyllum robustum Maxim. (Berberidaceae), in the wild. The two beetle populations showed lower acceptance of and survivorship on the non-host plant (thistle) than on the normal host plant (blue cohosh). Furthermore, they differed significantly in their responses to thistle but not to blue cohosh. Even for the beetle population that more readily accepted thistle as adults, acceptance was moderate and the eclosion rate was low, indicating reduced performance on the non-host plant. Although studies have infrequently focused on non-host acceptance, this is likely common in phytophagous specialists and thus is a potentially important evolutionaryfactor,as it maydeterminethefuturedirectionoffood-rangeevolution.

Synthetic Studies Towards Caulophyllumine and its Derivatives

Caulophyllum thalictroides (L.) Michx. (Blue Cohosh) is a popular herb, roots and rhizomes of which have been extensively used for women's health [1] and it is also considered a poisonous plant. A detailed phytochemical analysis revealed that alkaloids and saponins are the major components responsible for its pharmacological effects. In addition to their biological activity, recently we have demonstrated that the piperidine alkaloid isolated from Blue Cohosh, Caulophyllumine B inhibits the major drug metabolizing P450 (Cyp450) enzymes [2]. In continuation of our efforts in safety and efficacy of dietary supplements, we need Caulophyllumine B and its analogs. To achieve these piperidine based alkaloids here we propose and demonstrate a four step synthesis starting from commercially available 2-piperidinone. Furthermore, the flexibility of the current strategy to introduce any substituted aromatic ring attached to piperidine scaffold allows construction of various structurally similar natural products and its analogs. Our synthetic strategy and the full chemical details will be presented.

Anti-Inflammatory Effect of Triterpene Saponins Isolated from Blue Cohosh (Caulophyllum thalictroides)

Blue cohosh has been used as a medicinal herb in eastern North America. It was commonly used as traditional medicines for the treatment of menopausal symptoms, rheumatic pain, and as anti-inflammatory remedy. Particularly, extract of blue cohosh roots has been used as anti-inflammatory antipyretic in traditional medicines. In the present study, we investigated the effects of blue cohosh components on the suppressive expression of iNOS or proinflammatory cytokines after the activation of microglia with lipopolysaccharide (LPS). The expression of iNOS, TNF-α, IL-1β, and IL-6 was determined by western blotting or gene expression. Blue cohosh treatment suppressed the elevation of LPS-induced iNOS expression in a concentration-dependent manner in microglia cells. Blue cohosh constituents also suppressed the expression of TNF-α, IL-1β, and IL-6. In addition, blue cohosh extract suppressed the expression of COX-2, iNOS, and proinflammatory cytokines in adrenal glands of mice. These results demonstrate that constituents of blue cohosh exert anti-inflammatory effects through the inhibition of expression of iNOS and proinflammatory cytokines. Therefore, blue cohosh may have therapeutic potential for the treatment of inflammation-related diseases.

Management of Post Menstrual Syndromes: From Traditional Knowledge to Evidence-Based Medicine

Plants were and are still widely used for a number of pathologies affecting women health, particularly post menstrual syndromes (PMS). PMS refers to a diverse set of clinical symptoms and nearly omnipresent in the woman of reproductive age and can impinge on women's interpersonal relationships, social behavior, work absenteeism, and work productivity [1]. In addition to conventional FDA approved drugs, a plethora of other selections are imperative to reflect on for women who prefer natural alternative and complementary therapies or for whom conventional remedies are contraindicated [2]. Indeed, prior to the introduction of modern therapy, a panoply of medicinal herbs such as Kacip Fatima, Vitex, Yam, Licorice, Alfalfa, Chamomile, Dong-Quai, Evening Primrose, Ginkgo, Water-Willow and Cohosh have been used predominantly to treat or relief PMS. Traditional Chinese medicine has been prescribing herbs and herbal formulas since time immemorial; for instance Angelica (Dang Gui) has been widely used by Chinese and Japanese women for centuries. It is well-known for regulating menstrual cycles, eliminating the discomfort of premenstrual syndromes, and relieving menstrual cramps. Medicinal plants thus tend to represent a safe alternative to current hormone or drug therapy used to manage PMS symptoms. Many of these herbals formulas were geared towards regulating hormonal cycle and some recently being reported to have estrogen and/or progesterone-like effects [3-5]. Other less popular herbs that have been used successfully to decrease nervous tension include passion-flower, valerian, oatgrass, lemon-balm and skull-cap [6]. One phytotherapeutic combination; dandelion root/leaf- Taraxum officinale, milk or blessed thistle- Cnicus benedictus, Vitex- Vitex agnus-castus, black or blue Cohosh- Cimcifuga racemosa and Caulophylum thalictroides, Dong-Quai - Angelica sinensis and wild-Yam - Dioscorea villosa, is prescribed by phytotherapists and/or traditional healers as a polyherbal tea (1 tsp. of the herbal formula, one part each, in 1 cup of boiling water thrice daily) or in tincture (1/2 tsp. 3 to 4 times daily). However, Vitex also known as chaste tree berry, has attracted much consideration and comprehensively tested in randomized controlled trials; [1, 7-8] and reported to exhibit dopaminic agonist, inhibiting prolactin and increasing estrogen secretions and its flavonoids ligands to benzodiazepine receptors- thereby depicting antidepressant and anxiolytic properties [1]. Chaste berry fruit extract has also been shown to correct prolactin levels in latent hyperprolactinaemia via dopamine receptors. Vitex formulation (Agnolyt®) has been reported to be superior to pyridoxine in reducing premenstrual tension, whereas Femicur® (dried extract of Vitex) decreased and/or ceased mastalgia, associated to PMS; both tested in randomized controlled clinical trials [7, 8]. Nonetheless, many of the above-mentioned mono or poly-phytotherapeutic combinations are not recommended during pregnancy and possible hormonal effects through breast milk (some via prolactin inhibition) [3]. Additionally, extensive and scientific-based clinical research into the use of herbal therapies for premenstrual disorders, specifically in adolescents is unfortunately sparse. To this effect, phytotherapies for PMS can be given due consideration provided they are prescribed by trained professionals following rigorous high-quality clinical testing and with optimal dosing standards but avoided concurrently with conventional medications. Additionally, it is believed that it is of uttermost importance for medical practitioners to be aware of such herbal therapies and any innate potential drug-herb interactions and/or side effects in an endeavor to offer alternatives to women.

The clinical spectrum and outcome of accidental wildfowl-mediated nicotinic plant poisoning.

Sir, I read with much interest the case report by Bellomo et al. [1]. I would like to make two comments: (i) a toxicological analysis on biological specimens, such as urine and serum, should have been done in order to increase the diagnostic accuracy [2] and (ii) the description of the clinical spectrum and outcome of the disease made by the authors is misleading because it can induce the readers to consider it a mild disease. Actually, the clinical spectrum and outcome of accidental wildfowl-mediated (quails, skylarks, chaffinches, robins) nicotinic plant poisoning are very large and variable. Plants containing nicotine and nicotine-like alkaloids that have been reported to be poisonous to humans include Conium maculatum, Nicotiana glauca and Nicotiana tabacum, Laburnum anagyroides and Caulophyllum thalictroides [3]. They contain the toxic alkaloids nicotine, anabasine, cytosine, n-methylcytisine, coniine, n-methylconiine and gamma-coniceine [3]. These alkaloids act agonistically at nicotinic-type acetylcholine (cholinergic) receptors. The nicotinic-type acetylcholine receptor can vary both in its subunit composition and in its distribution within the body (the central and autonomic nervous systems, the neuromuscular junctions and the adrenal medulla). Agonistic interactions at these variable sites may explain why alkaloids have diverse effects depending on the administered dose and duration of exposure [3]. Twenty years ago, we reported the largest series ever published of accidental hemlock poisoning [4]: it included 17 patients poisoned in Apulia (South Italy) between 1972 and 1990: in 14 of them, toxicological analysis was performed on the same day of hospital admission which detected coniine. Neurotoxic effects were observed in all cases: in six coniine-poisoned patients, flaccid paralysis involved respiratory muscles following the typical curare progression. In others of our coniine-intoxicated subjects, muscle hypotonia without loss of voluntary movements was observed, probably because of the smaller amounts of poison ingested. Nicotinic effects of coniine were also present: stimulation (sialorrhoea, nausea, vomiting, abdominal cramps, diarrhoea) being followed by mucosal dryness, gastrointestinal hypotonia and mydriasis [4]. The 17 patients intoxicated by coniine experienced muscle pains, which started some hours after the ingestion of the poison (rhabdomyolysis). Five patients developed the clinical features of acute kidney injury from the first day of intoxication. Ten patients were simply treated on forced diuresis sometimes with gastrolavage; six patients were transferred to the intensive care unit and required artificial respiration; the five subjects who suffered acute kidney injury were treated with haemodialysis or peritoneal dialysis; in one patient, plasmaphaeresis seems to have improved an initially severe clinical picture. The outcome was favourable in 13 cases: 4 patients (∼24%) died, 3 of them from complications linked to the acute kidney injury; the last one died 36 h after the poisoning because of respiratory muscle paralysis [4]. In conclusion, the clinical spectrum of accidental wildfowl-mediated nicotinic plant poisoning is very large and the outcome is variable, ranging from complete recovery to death.

Analytical methods for determination of magnoflorine and saponins from roots of Caulophyllum thalictroides (L.) Michx. Using UPLC, HPLC and HPTLC

Analytical methods including HPLC, UPLC and HPTLC are presented for the determination of major alkaloid and triterpene saponins from the roots of Caulophyllum thalictroides (L.) Michx. (blue cohosh) and dietary supplements claiming to contain blue cohosh. A separation by LC was achieved using a reversed phase column, PDA with ELS detection, and ammonium acetate/acetonitrile gradient as the mobile phase. Owing to their low UV absorption, the triterpene saponins were detected by evaporative light scattering. The eight triterpene saponins (cauloside H, leonticin D, cauloside G, cauloside D, cauloside B, cauloside C, cauloside A and saponin PE) and the alkaloid magnoflorine could be separated within 35 min using HPLC method and within 8.0 min using UPLC method with detection limits of 10 μg/mL for saponins and 1 μg/mL for magnoflorine. The detection wavelength was 320 nm for magnoflorine and ELS detection was used for the eight saponins. The methods were also successfully applied to analyze different dietary supplements. For the products claiming to contain blue cohosh, there was a significant variability in the amounts of triterpene saponins detected. Calculations based on the analysis results for dietary supplements showed that maximum daily intake of alkaloid and saponins vary with the form (solids/liquids) and recommended doses according to the products label. Intakes varied from 0.57 to 15.8 mg/day for magnoflorine and from 5.97 to 302.4 mg/day for total saponins. LC–mass spectrometry coupled with electrospray ionization (ESI) method is described for the identification and confirmation of nine compounds in plant samples and dietary products. A HPTLC method was also developed for the fast chemical fingerprint analysis of C. thalictroides samples.

Complementary and alternative medicine for induction of labour

Induction of labour is a common obstetric procedure. Some women are likely to turn to complementary and alternative medicine in order to avoid medical intervention. The aim of this paper is to examine the scientific evidence for the use of complementary and alternative medicine to stimulate labour. An initial search for relevant literature published from 2000 was undertaken using a range of databases. Articles were also identified by examining bibliographies. Most complementary and alternative medicines used for induction of labour are recommended on the basis of traditional knowledge, rather than scientific research. Currently, the clinical evidence is sparse and it is not possible to make firm conclusions regarding the effectiveness of these therapies. There is however some data to support the use of breast stimulation for induction of labour. Acupuncture and raspberry leaf may also be beneficial. Castor oil and evening primrose oil might not be effective and possibly increase the incidence of complications. There is no evidence from clinical trails to support homeopathy however, some women have found these remedies helpful. Blue cohosh may be harmful during pregnancy and should not be recommended for induction. Other complementary and alternative medicine (CAM) therapies may be useful but further investigation is needed. More research is needed to establish the safety and efficacy of CAM modalities. Midwives should develop a good understanding of these therapies, including both the benefits and risks, so they can assist women to make appropriate decisions.

Teratogenic Effects of Blue Cohosh (Caulophyllum thalictroides) in Japanese Medaka (Oryzias latipes) Are Probably Mediated through GATA2/EDN1 Signaling Pathway

Blue cohosh (Caulophyllum thalictroides) (BC) has been used widely to induce labor and to treat other uterine conditions. However, the safety and effectiveness of this herbal product has not yet been evaluated by the US Food and Drug Administration (FDA). Several conflicting reports indicated that the root extract of BC is a teratogen and, by some unknown mechanisms, is able to induce cardiovascular malfunctions in new-born babies. To understand the mechanism, we have used Japanese medaka (Oryzias latipes) embryo-larval development as the experimental model and the methanolic extract of BC root as the teratogen. The embryo mortality, hatching efficiency, and morphological abnormalities in craniofacial and cardiovascular systems are considered for the evaluation of BC toxicity. Our results indicate that BC is able to disrupt cardiovascular and craniofacial cartilage development in medaka embryo in a dose and developmental stage-specific manner. Moreover, embryos in precirculation are to some extent more resistant to BC than ones with circulation. By using subtractive hybridization, we have observed that gata2 mRNA was differentially expressed in the circulating embryos after BC treatment. As GATA-binding sequences are required for the expression of the endothelin1 (edn1) gene and edn1 expressed in blood vessels and craniofacial cartilages, we have extended our investigations to edn1 gene expression regulation by BC. We found that edn1, furin1, and endothelin receptor A (ednrA) genes are developmentally regulated; endothelin converting enzyme mRNA (ece1) maintained a steady-state level throughout development. Circulating medaka embryos (3 days post fertilization, dpf) exposed to BC (10 microg/mL) for 48 h have increased levels of gata2, ece1, and preproenodthelin (preproedn1) mRNA contents; however, other mRNAs (furin and ednrA) remained unaltered. Therefore, the enhanced expression of gata2 mRNA followed by ece1 and preproedn1 mRNA by BC might be able to induce vasoconstriction and cardiovascular defects and disrupt craniofacial cartilages in medaka embryos. We conclude that cardiovascular and craniofacial defects in medaka embryogenesis by BC are probably mediated through a GATA2-EDN1 signaling pathway.