Black Cohosh Research Articles

Alternative approach to species identification of Actaea racemosa L. (syn. Cimicifuga racemosa (L.) Nutt., black cohosh) herbal starting material: UV spectroscopy coupled with LDA

The North American Actaea racemosa L. (syn. Cimicifuga racemosa (L.) Nutt., commonly known as black cohosh), considered to be a more “natural” alternative to conventional therapies, is used to relieve menopausal symptoms. The high demand for plant material has led to problems with substitution/adulteration of raw material of wholesale origin. The authenticity of the starting material is crucial for the herbal product’s efficacy and safety, and tests on identity and substitution are integral parts of cGMP guidelines. Consequently, there is a need for economical and easy-applicable test procedures. The aim of this study is to reveal the capability of the well-established UV spectroscopy coupled with a multivariate classification procedure to serve as a tool for the identification of A. racemosa. We built a classification model applying linear discriminant analysis (LDA) to distinguish between A. racemosa and its common substitutes. The model showed a high level of accuracy predicting 100% of the samples correctly. Our results indicate that UV spectroscopy shows potential for the development of possible additional authentication methods for this herbal starting material.

Economical, Plain, and Rapid Authentication of Actaea racemosa L. (syn. Cimicifuga racemosa, Black Cohosh) Herbal Raw Material by Resilient RP-PDA-HPLC and Chemometric Analysis.

The medicinal plant Actaea racemosa L. (Ranunculaceae, aka black cohosh) is widely used to treat climacteric complaints as an alternative to hormone substitution. Recent trials prove efficacy and safety of the approved herbal medicinal products from extracts of pharmaceutical quality. This led to worldwide increasing sales. A higher demand for the plant material results in problems with economically motivated adulteration. Thus, reliable tools for herbal drug authentication are necessary. To develop an economical, plain, and rapid method to distinguish between closely related American and Asian Actaea species, using securely established and resilient analytical methods coupled to a chemometric evaluation of the resulting data. We developed and validated a RP-PDA-HPLC method including an extraction by ultra-sonication to determine the genuine contents of partly hydrolysis-sensitive polyphenols in Actaea racemosa roots and rhizomes, and applied it to a large number of 203 Actaea samples consisting of seven species. We were able to generate reliable data with regards to the polyphenolic esters in the samples. The evaluation of this data by principle component analysis (PCA) made a discrimination between Asian Actaea species (sheng ma), one American Actaea species (Appalachian bugbane), and A. racemosa possible. The developed RP-PDA-HPLC method coupled to PCA is an excellent tool for authentication of the Actaea racemosa herbal drug, and can be a powerful addition to the TLC methods used in the dedicated pharmacopoeias, and is a promising alternative to expensive and lots of expertise requiring methods. Copyright © 2016 John Wiley & Sons, Ltd.

Noni leaf and black tea enhance bone regeneration in estrogen-deficient rats

ObjectiveBlack tea and Nonileaf are among the dietary compounds that can benefit patients with bone resorption disorders. Their bone regeneration effects and their mechanisms were studied in estrogen-deficient rats. MethodsNoni leaves (three doses) and black tea water extracts were fed to ovariectomized rats for 4 mo, and their effects (analyzed via mechanical measurements, micro-computed tomography scan, and reverse transcriptase polymerase chain reaction mRNA) were compared with Remifemin (a commercial phytoestrogen product from black cohosh). ResultsThe water extracts (dose-dependently for noni leaves) increased bone regeneration biomarker (runt-related transcription factor 2, bone morphogenetic protein 2, osteoprotegerin, estrogen receptor 1 [ESR1], collagen type I alpha 1A) expressions and reduced the inflammatory biomarkers (interleukin-6, tumor necrosis factor-α, nuclear factor [NF]-κB, and receptor activator of NF-κB ligand) mRNA expressions/levels in the rats. The extracts also improved bone physical and mechanical properties. The extracts demonstrated bone regeneration through improving bone size and structure, bone mechanical properties (strength and flexibility), and bone mineralization and density. ConclusionsThe catechin-rich extract favored bone regeneration and suppressed bone resorption. The mechanisms involved enhancing osteoblast generation and survival, inhibiting osteoclast growth and activities, suppressing inflammation, improving bone collagen synthesis and upregulating ESR1 expression to augment phytoestrogenic effects. Estrogen deficiency bone loss and all extracts studied (best effect from Morinda leaf at 300 mg/kg body weight) mitigated the loss, indicating benefits for the aged and menopausal women.

Escitalopram versus black cohosh for relieving hot flashes in nondepressed menopausal women

Escitalopram versus black cohosh for relieving hot flashes in nondepressed menopausal women

Дозозависимые эффекты экстракта Cimicifuga racemosa Ze 450 (препарат симидона) в лечении климактерических жалоб рандомизированное плацебо-контролируемое исследование

Since large epidemiological studies with long-term hormonal replacement therapy have shown a small but significantly increased risk for the development of invasive breast cancer, there is an increasing interest in nonhormonal treatment modalities for patients with climacteric symptoms. Cimicifuga racemosa is a perennial medicinal plant native to North America where it has been used for centuries in indigenous medicine for the treatment of various conditions. Extracts from Cimicifuga racemosa (CR, synonym Actaea racemosa) have shown efficacy in trials in women with menopausal symptoms. Yet, dose dependency remains unclear. Therefore, 180 female outpatients with climacteric complaints were treated for 12 weeks in a randomized, double-blind, placebo-controlled, 3-armed trial (CR extract Ze 450 in 6.5 mg or 13.0 mg, or placebo). The study took place in four outpatient clinics. Primary outcome was the difference in menopausal symptoms (vasomotor, psychological, and somatic), assessed by the Kupperman Menopausal Index between baseline and week 12. Secondary efficacy variables were patients’ self-assessments of general quality of life, responder rates, and safety. Compared to placebo, patients receiving Ze 450 showed a significant reduction in the severity of menopausal symptoms in a dose-dependent manner from baseline to endpoint (mean absolute differences 17.0 (95% CI 14.65–19.35) score points, р < 0.0001 for 13.0 mg; mean absolute differences 8.47 (95% CI 5.55–11.39) score points, р = 0.0003 for 6.5 mg). Quality of life and responder rates corresponded with the main endpoint. Changes in menopausal symptoms and quality of life were inversely correlated. Reported adverse events and clinical laboratory testing did not raise safety concerns. The CR extract Ze 450 is an effective and well-tolerated nonhormonal alternative to hormone treatment for symptom relief in menopausal women.

Black cohosh inhibits 17β-estradiol-induced cell proliferation of endometrial adenocarcinoma cells

This study was conducted to investigate the effect of black cohosh (BC) extract on the proliferation and apoptosis of Ishikawa cells. Ishikawa human endometrial adenocarcinoma cells were treated with or without BC (1, 5, 10 and 25 μM) and cell proliferation and cytotoxicity were measured by CCK-8 assays and flow cytometry analysis. Additionally, Ishikawa cells were treated with 17β-estradiol (E2), E2 + progesterone and E2 + BC (5 and 10 μM) and the effect of BC and progesterone on E2-induced cell proliferation was analyzed. BC decreased the proliferation of Ishikawa cells at a dose-dependent rate compared with the control group (p < 0.05). The proliferation of Ishikawa cells increased in the presence of E2, whereas the subsequent addition of progesterone or BC decreased proliferation to the level of the control group (p < 0.05). The inhibitory effect of BC on E2-induced cell proliferation was greater than the inhibitory effect of progesterone. In conclusion, BC induces apoptosis in Ishikawa cells and suppresses E2-induced cell proliferation in Ishikawa cells. BC could be considered a candidate co-treatment agent of estrogen-dependent tumors, especially those involving endometrial cells.

Authentication of the botanical origin of Western herbal products using Cimicifuga and Vitex products as examples.

Various herbal medicines have been developed and used in various parts of the world for thousands of years. Although locally grown indigenous plants were originally used for traditional herbal preparations, Western herbal products are now becoming popular in Japan with the increasing interest in health. At the same time, there are growing concerns about the substitution of ingredients and adulteration of herbal products, highlighting the need for the authentication of the origin of plants used in herbal products. This review describes studies on Cimicifuga and Vitex products developed in Europe and Japan, focusing on establishing analytical methods to evaluate the origins of material plants and finished products. These methods include a polymerase chain reaction-restriction fragment length polymorphism method and a multiplex amplification refractory mutation system method. A genome-based authentication method and liquid chromatography-mass spectrometry-based authentication for black cohosh products, and the identification of two characteristic diterpenes of agnus castus fruit and a shrub chaste tree fruit-specific triterpene derivative are also described.Electronic supplementary materialThe online version of this article (doi:10.1007/s11418-016-1006-0) contains supplementary material, which is available to authorized users.

Actein protects against methylglyoxal-induced oxidative damage in osteoblastic MC3T3-E1 cells.

Methylglyoxal (MG) is an endogenous product of glucose metabolism known to be toxic to cells and to be present in elevated concentrations under certain pathophysiological conditions. In the present study the effect of actein isolated from black cohosh on MG-induced cytotoxicity was investigated in MC3T3-E1 osteoblastic cells. Treatment of MC3T3-E1 osteoblastic cells with actein prevented MG-induced cell death and the production of intracellular reactive oxygen species (ROS), mitochondrial superoxide, inflammatory cytokines and soluble receptor for advanced glycation end-products (sRAGE). In addition, actein increased the activity of glyoxalase I and levels of reduced glutathione (GSH) and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). These findings suggest that actein protects against MG-induced cell damage by reducing oxidative stress and increasing MG detoxification. Treatment with actein prior to MG exposure reduced MG-induced mitochondrial dysfunction by preventing mitochondrial membrane potential dissipation and adenosine triphosphate (ATP) loss. Additionally, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1) and nitric oxide (NO) levels were significantly increased by actein, suggesting that actein may induce mitochondrial biogenesis. This study demonstrates that actein reduces MG-induced damage in osteoblastic MC3T3-E1 cells by enhancing antioxidant defenses, the glyoxalase system and mitochondrial biogenesis. © 2016 Society of Chemical Industry.

Botanical Ingredient Adulteration: Efforts By The ABC-AHP-NCNPR Botanical Adulterants Program To Raise Awareness Of Current Issues And Provide Solutions To The Problem

As the market for herbal medicines and dietary supplements increases, so do confirmed reports of undisclosed ingredients being added to botanical raw materials, extracts, essential oils, and finished botanical-based consumer products. These problems present a significant challenge to the global botanical medicine and herbal supplement industries and, more importantly, may put the health and safety of the consumer at risk. The ABC-AHP-NCNPR Botanical Adulterants Program (BAP) provides reviews on specific topics of adulteration, and a quarterly newsletter with program news, regulatory action with regard to adulteration, case reports of adulteration detailed by industry members, reports of adulteration and analytical technologies to detect adulteration published in the scientific literature, and upcoming educational events that touch upon the subject. The BAP has also published a number of Laboratory Guidance Documents (LGDs) in which analytical methods on botanicals and extracts in categories that are known to be adulterated are reviewed and evaluated for their ability to detect the suspected adulteration. As part of the series, LGDs on skullcap (Scutellaria lateriflora), bilberry (Vaccinium myrtillus) extract, and black cohosh (Actaea racemosa) have been published in 2015. The presentation will give an overview of the Program.

American Indian Botanicals As Possible Alternatives To Hormone Therapy During Menopause

Although pharmaceutical hormone therapy (HT) remains the standard clinical treatment for managing menopausal symptoms, many women seek alternatives such as botanical dietary supplements because HT has been associated with increased risks of breast cancer, coronary heart disease and stroke. The leading botanicals that women take for menopause are black cohosh and red clover, which were also traditionally used by American Indians. While these two botanicals have been investigated extensively, there are still numerous American Indian plants that lack scientific studies on their safety and efficacy. In collaboration with the Chicago Botanic Garden, 15 native plants were evaluated for potential women's health-related benefits. Amorpha canescens Pursh. (Fabaceae) – Leadplant, Echinocystis lobata (Michx.) Torr. & A. Gray (Cucurbitaceae) – wild cucumber, and Silphium perfoliatum L. (Asteraceae) - cup plant inflorescent tissue were screened for estrogenicity, chemopreventive, and anti-inflammatory potential based on American Indian ethnobotany and published biological data. Leadplant MeOH extract was selected as the best candidate for bioassay-guided fractionation due to dose-dependent (40, 20, 10, 5, 2.5, 1.25 µg/mL) anti-estrogenic and anti-inflammatory activity in the Ishikawa and Griess assays (n = 9). However, leadplant extract (20 µg/mL) demonstrated low activity in the NQO1 induction assay for chemopreventive potential (n = 6). Currently, bioassay guided-fractionation is being performed on leadplant to ascertain the active constituents.

The efficacy of Iranian herbal medicines in alleviating hot flashes: A systematic review

Hot flashes are the most common symptoms experienced by women around the time of menopause. Many women are interested in herbal medicines because of fear of side effects of hormone therapy. The aim of this systematic review was to assess the effectiveness of Iranian herbal medicines in alleviating hot flashes. MEDLINE (1966 to January 2015), Scopus (1996 to January 2015), and Cochrane Central Register of Controlled Trials (The Cochrane Library, issue 1, 2015) were searched along with, SID, Iran Medex, Magiran, Medlib and Irandoc. Nineteen randomized controlled trials met the inclusion criteria. Overall, studies showed that Anise (Pimpinella anisum), licorice (Glycyrrhizaglabra), Soy, Black cohosh, Red clover, Evening primrose, Flaxseed, Salvia officinalis, Passifloraitex Agnus Castus, Piascledine (Avacado plus soybean oil), St. John's wort (Hypericum perforatum), and valerian can alleviate the side effects of hot flashes. This research demonstrated the efficacy of herbal medicines in alleviating hot flashes, which are embraced both with people and health providers of Iran Therefore, herbal medicine can be seen as an alternative treatment for women experiencing hot flashes.

ENDOCRINE DILEMMA: Managing menopausal symptoms after breast cancer.

Managing the symptoms of menopause after a diagnosis of breast cancer offers some unique clinical challenges. For some women, vasomotor symptoms can be severe and debilitating, and hormone therapy is at least relatively contraindicated. Non-oestrogen therapies for hot flushes include SSRIs, clonidine, gabapentin and perhaps black cohosh extracts. Vulvovaginal atrophy can usually be alleviated by simple moisturizers, although some may need specialized physiotherapy such as vaginal dilators. In a small number, topical oestrogens may be the only treatment that works. The CO2 laser may be a novel, non-oestrogen therapy to alleviate this unpleasant symptom. Bone loss can be accelerated in some patients on AIs or those who had early menopause induced by chemotherapy.

Severe Hyponatremia Associated with Use of Black Cohosh during Prolonged Labor and Unsuccessful Home Birth

Introduction There has been an increase in the use of herbal supplements during pregnancy, which are frequently of unproven efficacy and safety. We present a case of severe hyponatremia and altered mental status associated with the use of black cohosh during prolonged labor. Case A 39-year-old primigravida at 385/7 weeks of gestational age presented to the emergency department after she became disoriented and lethargic while laboring at home with a midwife. She had consumed several doses of black cohosh to induce and augment labor. On presentation, she was nonverbal and unable to follow commands. Her serum sodium was 114 mmol/L (range, 132–145 mmol/L), serum osmolality was 253 mOsm/kg (range, 275–300 mOsm/kg), urine osmolality was 190 mOsm/kg (range, 300–900 mOsm/kg), and urine sodium was <10 mmol/L. The patient soon became uncooperative and combative and a cesarean section was performed. Postoperatively, she was transferred to the intensive care unit for monitoring and correction of her sodium. Her mental status returned to baseline and she was subsequently discharged home without further complication. Discussion Clinically significant hyponatremia associated with pregnancy is rare. Further investigation is needed to evaluate the safety and efficacy of black cohosh and other commonly used herbal supplements during pregnancy and labor.

Black Cohosh Ameliorates Metabolic Disorders in Female Ovariectomized Rats.

Estrogen deficiency is associated with metabolic derangements in menopausal women. Black cohosh has been widely used as an alternative therapy in the treatment of menopausal syndrome. However, its role in metabolism needs to be defined. The aim of the present study was to investigate the long-term effect of black cohosh on glucose and lipid metabolism in a rat model of post-menopause. Adult female Sprague-Dawley rats were sham operated (SHAM), ovariectomized (OVX), OVX with the treatment of estradiol valerate (OVX + E), or OVX with the treatment of isopropanolic black cohosh extract (OVX + iCR). Body weight, body composition, and blood glucose levels of the animals were monitored. The rats were then sacrificed after 3 months of the treatments. At the end of the experiment, OVX + iCR and OVX + E rats exhibited a significant decrease in body weight gain, body and abdominal fat mass, serum triglycerides levels, hepatic fat accumulation, and adipocyte hypertrophy compared with OVX rats. In addition, insulin resistance and glucose intolerance were improved in OVX + iCR but not in OVX + E rats. No hepatotoxicity was detected in OVX + iCR animals. Furthermore, western blot analysis suggested the increased lipolysis in adipose tissue of OVX + iCR and OVX + E rats. Data from in vitro experiments using cultured primary rat adipocytes also showed that black cohosh could affect lipolysis of adipocytes. In conclusion, the long-term treatment of black cohosh at a proper dosage ameliorated metabolic derangements in OVX rats. Thus, this drug is promising for the treatment of metabolic disorders in menopausal and post-menopausal women.

Effects of black cohosh on estrogen biosynthesis in hippocampus of non-human primates ex vivo in vitro and in human neuroblastoma cells in vitro

BackgroundEstrogens have neuroprotective properties. The aim of the study was to assess the impact of an isopropanolic extract of Cimicifuga racemosa (iCR), 17ß-estradiol (E2), testosterone (T) and Tibolone’s 3α-OH metabolite (Org4094) on local estrogen formation in hippocampus tissue from non-human primates ex vivo in vitro and human neuroblastoma cells (SH-SY5Y) in vitro.MethodsSH-SY5Y cells were incubated in RPMI 1640 medium containing 5 % steroid-depleted fetal calf serum for 3 days, and subsequently incubated in absence or presence of iCR at 10 μg/ml (n = 5) and 1 μg/ml (n = 5), E2 at 10−8 M (n = 5), and 10−6 M (n = 5), or T at 10−8 M (n = 5), and 10−6 M (n = 5), respectively, at 37 °C for either 24 h or directly in cell extracts. Hippocampus tissue from healthy female cynomolgus macaques (n = 14) was homogenized and treated with iCR, E2 and Org4049 accordingly. STS activity was evaluated by incubating homogenized brain cells and tissue with [3H]-estrone sulfate and separating the products estrone (E1) and E2 by thin layer chromatography. STS activity was expressed as total estrogen formation (E1 + E2) fmol/mg of protein/min. Statistical comparisons were made using unpaired T-Test for comparing two sets of data and ANOVA to compare many groups at once. A p value < 0.05 was considered to be significant different.ResultsBasal total estrogen formation was significantly higher in proliferative SH-SY5Y cells (1350.06 ± 109 E1 + E2 fmol/mg of protein/min) compared to hippocampus tissue (37.83 ± 3.9 E1 + E2 fmol/mg of protein/min; p < 0.01). ICR exerted a bidirectional action with an immediate strong inhibitory effect being followed by a stimulation of STS activity (85 % increase). E2 had a bidirectional dose-dependent long-term effect on STS activity (−23 % reduction and 18 % increase). T and Org4094 had an immediate strong inhibitory effect on STS activity that further maintained with 24 h T treatment (30 % decrease).ConclusionsLocal estrogen formation within brain cells and tissue may be modulated by black cohosh, 17ß-estradiol, testosterone, and Tibolone’s 3α-OH metabolite, respectively. The clinical implication of this finding has to be elucidated.

Cycloartane Triterpenes from the Aerial Parts of Actaea racemosa.

Investigating the phytochemical equivalence of the aerial parts of Actaea racemosa (syn. Cimicifuga racemosa) relative to the widely used roots/rhizomes, this study provides a perspective for the potential use of renewable ("green") plant parts as a source of black cohosh botanical preparations. In addition to the characterization of Nω-methylserotonin as one representative marker of the Actaea alkaloids, nine cycloartane triterpenes were isolated and characterized, including the two new triterpene glycosides (1S,15R)-1,15,25-trihydroxy-3-O-β-d-xylopyranosyl-acta-(16S,23R,24R)-16,23;16,24-binoxoside (1) and 3-O-α-l-arabinopyranosyl-(1S,24R)-1,24,25-trihydroxy-15-oxo-acta-(16R,23R)-16,23-monoxoside (2). Their structures were elucidated by spectroscopic data interpretation. The relative configuration of 1 was deduced by (1)H iterative full-spin analysis (HiFSA), making it the first example of the complete analysis of the complex (1)H NMR spectrum of a triterpene glycoside. In addition to the new compounds 1 and 2, the aerial plant parts were shown to contain the previously known binoxosides 3, 4, 6, and 7, the monoxoside 8, and the binoxols 5 and 9. Overall, the metabolome of the aerial plant parts consists of a variety of Actaea triterpenes, similar to those found in roots/rhizomes, a tendency toward C-1 and C-7 hydroxylation of the cycloartanol skeleton, a greater abundance of aglycones, and the presence of comparable amounts of Nω-methylserotonin.

Role of the ER/NO/cGMP Signaling Pathway in the Promotion of Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells by Actaea racemosa Extract.

Purpose/Objective. To investigate the effect of Actaea racemosa (AR) extract on in vitro osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) via the ER/NO/cGMP signaling pathway. Methods/Materials. Rat BMSCs were treated with osteogenic differentiation-inducing medium containing AR; estrogen receptor antagonist, ICI 182,780 (10−6 mol/L); and nitric oxide synthase inhibitor, L-nitro arginine methyl ester (L-NAME, 6 × 10−3 mol/L). Markers of osteogenic differentiation (alkaline phosphatase [ALP] activity, osteocalcin secretion, and calcium ion deposit levels) and the levels of key signaling molecules (nitric oxide synthase [NOS], nitric oxide [NO], and cyclic guanosine monophosphate [cGMP]) were assessed. Results. AR (10−1–10−6 g/L) increased ALP activity in a dose-dependent manner, and the highest ALP, osteocalcin, and osteoprotegerin activities were achieved at an AR concentration of 10−4 g/L. Therefore, the concentration of 10−4 g/L was used for promoting osteogenic differentiation of BMSCs in subsequent analyses. At this concentration, AR increased the levels of NO and cGMP, and such effects could be blocked by the estrogen receptor antagonist (ICI 182,780) and nitric oxide synthase inhibitor (L-NAME). Conclusion. AR induced osteogenic differentiation of rat BMSCs through the ER/NO/cGMP signaling pathway. This finding provides the theoretical foundation for the mechanism of AR in the treatment of postmenopausal osteoporosis.

Comparison of Flow Injection MS, NMR, and DNA Sequencing: Methods for Identification and Authentication of Black Cohosh (Actaea racemosa).

Flow injection mass spectrometry and proton nuclear magnetic resonance spectrometry, two metabolic fingerprinting methods, and DNA sequencing were used to identify and authenticate Actaea species. Initially, samples of Actaea racemosa from a single source were distinguished from other Actaea species based on principal component analysis and soft independent modeling of class analogies of flow injection mass spectrometry and proton nuclear magnetic resonance spectrometry metabolic fingerprints. The chemometric results for flow injection mass spectrometry and proton nuclear magnetic resonance spectrometry agreed well and showed similar agreement throughout the study. DNA sequencing using DNA sequence data from two independent gene regions confirmed the metabolic fingerprinting results. Differences were observed between A. racemosa samples from four different sources, although the variance within species was still significantly less than the variance between species. A model based on the combined A. racemosa samples from the four sources consistently permitted distinction between species. Additionally, the combined A. racemosa samples were distinguishable from commercial root samples and from commercial supplements in tablet, capsule, or liquid form. DNA sequencing verified the lack of authenticity of the commercial roots but was unsuccessful in characterizing many of the supplements due to the lack of available DNA.

Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it.

Electropharmacogram of Sceletium tortuosum extract based on spectral local field power in conscious freely moving rats

Ethnopharmacological relevanceThe endemic succulent South African plant, Sceletium tortuosum (L.) N.E. Br. (synonym Mesembryanthemum tortuosum L.), of the family Mesembryathemaceae, has an ancient oral tradition history of use by San and Khoikhoi people as an integral part of the indigenous culture and materia medica. A special standardized extract of Sceletium tortuosum (Zembrin®) has been developed and tested pre-clinically in rats, and clinically in healthy subjects. Aim of the studyThe present investigation aimed at the construction of electropharmacograms of Zembrin® in the presence of three dosages (2.5, 5.0 and 10.0mg/kg), and comparative electropharmacograms and discriminatory analyses for other herbal extracts, citicoline and rolipram. Material and methodsSeventeen adult Fischer rats were each implanted with a set consisting of four bipolar concentric steel electrodes fixed by dental cement and three screws driven into the scalp. After two weeks of recovery from surgery the animals were adapted to oral administration by gavage and to experimental conditions (45min pre-drug period and 5h of recording after a rest of 5min for calming down). Data were transmitted wirelessly and processed using a Fast Fourier Transformation (FFT). Spectral power was evaluated for 8 frequency ranges, namely delta, theta, alpha1, alpha2, beta1a, beta1b, beta2 and gamma power. ResultsZembrin® dose dependently attenuated all frequency ranges, to varying degrees. The most prominent was the statistically significant reduction in alpha2 and beta1a waves, correlated with activation of the dopaminergic and glutamatergic transmitter systems respectively. This feature is common to all synthetic and herbal stimulants tested to date. The second strongest effects were reduction in both the delta and the theta frequency ranges, correlated with changes in the cholinergic and norepinephrine systems respectively, a pattern seen in preparations prescribed for neurodegenerative diseases. Theta wave reduction in common with the delta, alpha2 and beta1 attenuation has been noted for analgesic drugs. Attenuation of alpha1 waves emerged during the highest dosage in all brain areas, a feature seen in all antidepressants. DiscussionThe electropharmacogram of Zembrin® was compared to the electropharmacograms of herbal extracts archived in our database. Extracts of Oenothera biennis and Cimicifuga racemosa gave a very similar electropharmacograms to that of Zembrin®, and extracts of Ginkgo biloba and Rhodiola rosea gave rather similar electropharmacograms to Zembrin®. Linear discriminant analysis confirmed these similarities and demonstrated that all three dosages of Zembrin® plotted in close neighbourhood to each other. Citocoline, a synthetic compound originally developed for cognitive enhancement, had a similar electropharmacogram to Zembrin®. Similarity to the electropharmacograms of the synthetic phosphodiesterase-4 inhibitor, rolipram, suggests Zembrin® has antidepressant and cognitive function enhancing potential. ConclusionThe combined results from the electropharmacograms and comparative discriminatory analyses suggest that Zembrin® has dose dependent activity, with potential applications as a cognitive function enhancer, as an antidepressant, and as an analgesic.