Black Cohosh Research Articles

Drug Interactions with Herbal Medicines

In recent years, the issue of herbal medicine-drug interactions has generated significant concern. Such interactions can increase the risk for an individual patient, especially with regard to drugs with a narrow therapeutic index (e.g. warfarin, ciclosporin and digoxin). The present article summarizes herbal medicine-drug interactions involving mainly inhibition or induction of cytochrome P450 enzymes and/or drug transporters. An increasing number of in vitro and animal studies, case reports and clinical trials evaluating such interactions have been reported, and the majority of the interactions may be difficult to predict. Potential pharmacodynamic and/or pharmacokinetic interactions of commonly used herbal medicines (black cohosh, garlic, Ginkgo, goldenseal, kava, milk thistle, Panax ginseng, Panax quinquefolius, saw palmetto and St John's wort) with conventional drugs are presented, and sometimes the results are contradictory. Clinical implications of herbal medicine-drug interactions depend on a variety of factors, such as the co-administered drugs, the patient characteristics, the origin of the herbal medicines, the composition of their constituents and the applied dosage regimens. To optimize the use of herbal medicines, further controlled studies are urgently needed to explore their potential for interactions with conventional drugs and to delineate the underlying mechanisms.

Hops (Humulus lupulus) Inhibits Oxidative Estrogen Metabolism and Estrogen-Induced Malignant Transformation in Human Mammary Epithelial cells (MCF-10A)

Long-term exposure to estrogens including those in traditional hormone replacement therapy (HRT) increases the risk of developing hormone-dependent cancers. As a result, women are turning to over-the-counter (OTC) botanical dietary supplements, such as black cohosh (Cimicifuga racemosa) and hops (Humulus lupulus), as natural alternatives to HRT. The two major mechanisms which likely contribute to estrogen and/or HRT cancer risk are: the estrogen receptor-mediated hormonal pathway; and the chemical carcinogenesis pathway involving formation of estrogen quinones that damage DNA and proteins, hence initiating and promoting carcinogenesis. Because, OTC botanical HRT alternatives are in widespread use, they may have the potential for chemopreventive effects on estrogen carcinogenic pathways in vivo. Therefore, the effect of OTC botanicals on estrogen-induced malignant transformation of MCF-10A cells was studied. Cytochrome P450 catalyzed hydroxylation of estradiol at the 4-position leads to an o-quinone believed to act as the proximal carcinogen. Liquid chromatography/tandem mass spectrometry analysis of estradiol metabolites showed that 4-hydroxylation was inhibited by hops, whereas black cohosh was without effect. Estrogen-induced expression of CYP450 1B1 and CYP450 1A1 was attenuated by the hops extract. Two phenolic constituents of hops (xanthohumol, XH; 8-prenylnaringenin, 8-PN) were tested: 8-PN was a potent inhibitor, whereas XH had no effect. Finally, estrogen-induced malignant transformation of MCF-10A cells was observed to be significantly inhibited by hops (5 μg/mL) and 8-PN (50 nmol/L). These data suggest that hops extracts possess cancer chemopreventive activity through attenuation of estrogen metabolism mediated by 8-PN.

Oral administration of Cimicifuga racemosa extract attenuates psychological and physiological stress responses

Dried rhizomes of Cimicifuga racemosa (CR), which are known as black cohosh, have been widely used as herbal dietary supplements to treat menopausal symptoms. The present study examined the effect of CR extracts on human psychological and physiological responses to acute stress induced by mental arithmetic tests, by measuring the subjective stress intensity, the brain-wave patterns according to electroencephalography, and the concentrations of salivary chromogranin-A and cortisol. The experiments were performed double-blind and their order was counterbalanced. Treatment with CR significantly attenuated the elevated subjective perception of stress and the increased salivary chromogranin-A levels compared with placebo treatment. CR extract also rapidly recovered the decrease in alpha waveband induced by performing the mental arithmetic task. We therefore propose that CR extracts might be suitable for the prevention and treatment of stress-related disorders.

Oral Administration of Cimicifuga racemosa Extract Attenuates Immobilization Stress-Induced Reactions

Dried rhizomes of Cimicifuga racemosa (CR), known as black cohosh, have been widely used as a herbal dietary supplement in the treatment of menopausal symptoms. Here we used experimental mouse stress models to investigate the role of anti-stress food factors, and found that a CR extract had stress-relieving effects. A single oral administration of CR extract (1,000 mg/kg) significantly attenuated plasma corticosterone and aspartate aminotransferase (AST) levels that had increased as a result of enforced immobilization. Bioassay-guided fractionation of the CR extract resulted in the isolation of 10 triterpenes, among which actein, 23-epi-26-deoxyactein, and cimiracemoside F (100 mg/kg, per os) were shown to contribute to the anti-stress effects. Furthermore, the CR extract significantly prevented the development of water immersion stress-induced gastric mucosal ulcers in rats. We propose that the CR extract might be suitable for the prevention and treatment of stress-related disorders.

Menopause

This randomized, double-blind, placebo-controlled, multicenter clinical study investigated the efficacy and various safety aspects of a standardized proprietary isopropanolic extract of black cohosh (Remifemin) in a population of 304 postmenopausal women who met strict parameter guidelines that determined the inclusion criteria. This clinical study confirmed previous results, which clearly indicate the efficacy and tolerability of this proprietary black cohosh extract (Remifemin) in addressing menopausal symptoms, particularly hot flashes.

Oral administration of Cimicifuga racemosa extract affects immobilization stress-induced changes in murine cerebral monoamine metabolism

We investigated the effects of Cimicifuga racemosa (CR) plant extracts on the changes in levels of the cerebral monoamines norepinephrine (NE), dopamine (DA), and serotonin (5-HT), the respective metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA), and plasma corticosterone in mice subjected to acute immobilization stress. Single oral administration of the CR extract (1,000 mg/kg) significantly attenuated plasma corticosterone levels that had been increased as a result of enforced immobilization. Acute immobilization stress caused significant changes in the corresponding amine-to-metabolite ratios in the hypothalamus, hippocampus, and cortex; however, CR-extract treatment significantly attenuated the MHPG/NE change in the hypothalamus, and the 5-HIAA/5- HT changes in each region of the brain. Our results suggest that the CR extract interacts not only with the hypothalamic-pituitary-adrenal (HPA) axis but also with the sympathetic adrenomedullary (SAM) system under stress conditions. Thus the CR extract can alleviate acute stress responses by suppressing the changes of amine-to-metabolite ratio in brain.

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.

Cimicifuga racemosa alters behavior and PVN c-fos expression in ovariectomized rats subjected to the forced swimming test

Cimicifuga racemosa alters behavior and PVN c-fos expression in ovariectomized rats subjected to the forced swimming test

Effect of Black Cohosh on Genital Atrophy and Its Adverse Effect in Postmenopausal Women

Effect of Black Cohosh on Genital Atrophy and Its Adverse Effect in Postmenopausal Women Sung Nam Hong, M.D., Jin Ha Kim, M.D., Heung Yeol Kim, M.D., Ari Kim, M.D. Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyungkwan University School of Medicine, Changwon, College of Medicine, Kosin University, Busan, College of Medicine, Institute of Wonkwang Medical Science, Wonkwang University, Iksan, Korea

Deoxyactein Isolated from Cimicifuga racemosa protects osteoblastic MC3T3‐E1 cells against antimycin A‐induced cytotoxicity

Deoxyactein is one of the major constituents isolated from Cimicifuga racemosa. In the present study, we investigated the protective effects of deoxyactein on antimycin A (mitochondrial electron transport inhibitor)-induced toxicity in osteoblastic MC3T3-E1 cells. Exposure of MC3T3-E1 cells to antimycin A caused significant cell viability loss, as well as mitochondrial membrane potential dissipation, complex IV inactivation, ATP loss, intracellular calcium ([Ca(2+) ]i ) elevation and oxidative stress. Pretreatment with deoxyactein prior to antimycin A exposure significantly reduced antimycin A-induced cell damage by preventing mitochondrial membrane potential dissipation, complex IV inactivation, ATP loss, [Ca(2+) ]i elevation and oxidative stress. Moreover, deoxyactein increased the activation of PI3K (phosphoinositide 3-kinase), Akt (protein kinase B) and CREB (cAMP-response element-binding protein) inhibited by antimycin A. All these data indicate that deoxyactein may reduce or prevent osteoblasts degeneration in osteoporosis or other degenerative disorders.

Pharmacological mechanisms of black cohosh in Sprague–Dawley rats

BackgroundStudies indicate that extracts and purified components from black cohosh inhibit the growth of human breast cancer cells, but the molecular targets and signaling pathways have not yet been defined. PurposeThis study examines the pharmacological mechanisms and toxicological effects in the short term of the herb black cohosh on female Sprague–Dawley rats. Materials and methodsTo assess effects on gene activity and lipid content, we treated female Sprague–Dawley rats with an extract of black cohosh enriched in triterpene glycosides (27%) at 35.7 or 0mg/kg. Four animals for each group were sacrificed at 1, 6 and 24h after treatment; liver tissue and serum samples were obtained for gene expression and lipid analysis. ResultsMicroarray analysis of rat liver tissue indicated that black cohosh markedly downregulated mitochondrial oxidative phosphorylation genes. Phospholipid biosynthesis and remodeling, PI3-Kinase and sphingosine signaling were upregulated, driven largely by an upregulation of several isoforms of phospholipase C. Hierarchical clustering indicated that black cohosh clustered with antiproliferative compounds, specifically tubulin binding vinca alkaloids and DNA alkylators. In support of this, black cohosh repressed the expression of cyclin D1 and ID3, and inhibited the proliferation of HepG2, p53 positive, liver cancer cells. Black cohosh reduced the level of free fatty acids at 6 and 24h and triglycerides at 6h in the serum, but increased the free fatty acid and triglyceride content of the treated livers at 24h. ConclusionOur results suggest that black cohosh warrants further study for breast cancer prevention and therapy.

Mass spectrometric dereplication of nitrogen-containing constituents of black cohosh (Cimicifuga racemosa L.)

Black cohosh preparations are popular dietary supplements among women seeking alternative treatments for menopausal complaints. For decades, triterpene glycosides and phenolic acids have dominated the phytochemical and biomedical research on this plant. In this study, we provide evidence that black cohosh contains an unexpected and highly diverse group of secondary nitrogenous metabolites previously unknown to exist in this plant. Using a dereplication approach that combines accurate mass measurements, database searches and general knowledge of biosynthetic pathways of natural products, we identified or tentatively identified 73 nitrogen-containing metabolites, many of which are new natural products. The identified compounds belong to several structural groups including alkaloids, amides or esters of hydroxycinnamic acids and betains. Among the alkaloids, several classes such as guanidino alkaloids, isoquinolines and β-carbolines were identified. Fragmentation patterns for major compound classes are discussed, which provides a framework for the discovery of these compounds from other sources. Identification of alkaloids as a well-known group of bioactive natural products represents an important advance in better understanding of the pharmacological profile of black cohosh.

BLACK COHOSH RHIZOME AND PHYTOCHEMICAL PRODUCTION IN RESPONSE TO SHADING, SPACING, AND AGE

ISHS XXVIII International Horticultural Congress on Science and Horticulture for People (IHC2010): A New Look at Medicinal and Aromatic Plants Seminar BLACK COHOSH RHIZOME AND PHYTOCHEMICAL PRODUCTION IN RESPONSE TO SHADING, SPACING, AND AGE

Complementary and alternative medicine in the treatment of menopausal symptoms

A large number of women will pass through menopause each year. Women in menopausal transition experience a variety of menopausal symptoms. Although hormonal therapy remains the most effective treatment, side effects have been reported by several large studies. An increased number of women seek the use of complementary and alternative medicine (CAM) for treating menopausal symptoms. This review analyzes the evidence from systematic reviews, randomized controlled trials and epidemiological studies of using herbal medicine (Black cohosh, Dong quai, St John's wart, Hops, Wild yam, Ginseng, and evening primrose oil) and acupuncture for the treatment of menopausal symptoms. Evidence supporting the efficacy and safety of most CAM for relief of menopausal symptoms are limited. Future larger and better controlled studies testing the effectiveness of these treatments are needed.

Black Cohosh Induced Pancytopenia: Case Report

Abstract 4383 Introduction:Black cohosh (known as both Actaea racemosa and Cimicifuga racemosa), a member of the buttercup family is a perrenial plant that is native of North America. It has been widely used to relieve premenstrual problems, menstrual cramps and to control hot flushes and other menopausal symptoms. The mechanism of action of the black cohosh is not fully understood. Here, we report the case of a patient with pancytopenia related to the use of the black cohosh. Case Report:A 58 year old female patient with past medical history of dyslipidemia, presented with bruising after several months of taking black cohosh. Her complete blood count revealed a white blood cell count of 3.1×109/L (normal 3.5–11 ×109/l), hemoglobin of 10.6 g/dl (normal 11–15 g/dl), hematocrit of 31 % (normal 32–45%), mean corpuscular volume of 109 fL (normal 80–98 fl), platelets count of 37 000/μL (normal 150000–400000/μL). Her medications included lipitor, black cohosh and vitamin D. Her physical exam was remarkable only for bruising. Serum protein electrophoresis did not show any evidence of a monoclonal spike and a coomb's test was negative. She had normal immunoglobulins level, haptogloin, LDH, liver function tests, iron studies, vitamin B12 and folate. Her prothrombin and activated partial thromboplastin times were within reference range. Her peripheral smear showed macrocytic red blood cells and decreased platelets. Her bone marrow biopsy and aspirate showed a hypocellular bone marrow (cellularity of 25–30%), with a predominance of erythroid precursors that exhibit shift toward immaturity and mild to moderate megaloblastoid changes, moderately decreased myeloid precursors, slightly decreased megakaryocytes, and normal iron stores, there was no increase in the bone marrow blasts (0.6%). She also had a flow sent for paroxysmal nocturnal hemoglobinuria, which showed normal levels of expression of CD55 and CD59 of the neutrophils and the red cells. Upon presentation, the black cohosh was stopped. Following this, her white count, hemoglobin and platelets improved slowly (figures 1,2,3,) without any further interventions, but it took over 2 years for her counts to normalize. Conclusion:Black cohosh is an over the counter herbal medicine that has been widely used by women to control premenstrual symptoms, menstrual cramping and menopausal symptoms. Many side effects have been described in the past but its effect on the bone marrow has never been studied. In our patient, Black cohosh caused pancytopenia that was reversible; however the recovery was very slow. Disclosures:No relevant conflicts of interest to declare. [Display omitted] [Display omitted] [Display omitted]

Recovery of Black Cohosh (Actaea racemosa L.) Following Experimental Harvests

Since European colonization and subsequent commercialization of Appalachian medicinal and edible plants, millions of kilograms of plant material have been extracted from our forests, with little effort to manage these species as natural resources. Roots and rhizomes of black cohosh, a native Appalachian forest herb, are extensively harvested for treatment of menopausal symptoms. As nearly all cohosh sold commercially is collected from natural populations, the potential for harvest impacts is considerable. To better understand wild-harvest impacts and the likelihood of post-harvest recovery, we studied the effects of 2 to 4 y of experimental harvest on natural black cohosh populations in the George Washington-Jefferson National Forest in southwest Virginia. After 2 to 3 y of intense harvest (66% plant removal), we found significant reductions in foliage area, stem production, and mean and maximum plant height. The effects of moderately intense harvest (33%) were less clear, producing growth measures between, yet not significantly different from, control (non-harvest) and intensively harvested plots. After three successive years of experimental harvest, harvest treatments were terminated to assess population regrowth. Populations experiencing intensive harvest showed no evidence of recovery after 1 y. Results suggest that black cohosh is highly responsive to harvest intensity and that low to moderate harvest intensities and/or longer recovery periods will be necessary for prolonged and sustainable harvests at our study site. While this study has increased our understanding of harvest impacts on black cohosh, continued assessment is needed to determine the sustainability of low to moderate harvest levels and minimum recovery periods necessary for population reestablishment.

Black cohosh (Cimicifuga racemosa) relaxes the isolated rat thoracic aorta through endothelium-dependent and -independent mechanisms

Aim of the studyThe rhizome of the Cimicifuga racemosa (commonly known as black cohosh) has been used in treatment of climacteric complaints for decades in North America and Europe. A number of studies investigated the estrogenic potential of black cohosh, but its effectiveness is still controversial. Recently, it was reported that the extract of black cohosh acted as an agonist at the serotonin (5-HT) receptor and 5-HT derivative was isolated out of the black cohosh extract. Because it is well known that the 5-HT elicited the various cardiovascular effects including vasorelaxation, we investigated the vasorelaxant effects of the extract of black cohosh and its possible mechanisms of action. Materials and methodsThe extract of black cohosh (BcEx) was examined for its vasorelaxant effects in isolated rat aorta. The aortic rings were equilibrated under resting tension and induced reproducible contraction in organ bath. The control contraction was produced by 300nM NE, and then BcEx were added. In experiments where specific inhibitors were used, they were added 20min before NE contraction. ResultsBcEx elicited two phases of relaxation in rat aorta pre-contracted with norepinephrine. The first, a rapid relaxation, which occurred within seconds of BcEx administration, was eliminated by pretreatment with NG-nitro-l-arginine (l-NNA) or methylene blue. The endogenous NO synthase substrate l-Arg markedly reversed the action of l-NNA, indicating that BcEx elicited the vasorelaxant effect via the NO/cGMP pathway. The second, slowly developing relaxation was not affected by the endothelium denudation. BcEx-induced endothelium-independent vasorelaxation appears to involve the inhibition of calcium influx mediated by the opening of inward rectifier potassium channels. ConclusionsBcEx elicits the vasorelaxant effect via endothelium-dependent and -independent mechanisms and may contribute to a better understanding of a potential link between the use of black cohosh and its beneficial effects on vascular health.

Digitized assessment of mammographic breast density – Effects of continuous combined hormone therapy, tibolone and black cohosh compared to placebo

ObjectivesTo determine the effects of continuous combined hormone therapy, tibolone, black cohosh, and placebo on digitized mammographic breast density in postmenopausal women. Study designA prospective, double-blind, placebo-controlled study of 154 postmenopausal women randomized to estradiol 2mg/norethisterone acetate 1mg (E2/NETA), tibolone 2.5mg or placebo and a prospective, open, uncontrolled drug safety study, of which 65 postmenopausal women were treated with black cohosh. Mammograms, at baseline and after six months of treatment, were previously classified according to visual quantification scales. Main outcome measuresReanalysis of assessable mammograms by digitized quantification of breast density. ResultsTreatment groups were comparable at baseline. During treatment, both E2/NETA and tibolone significantly increased breast density (mean increase 14.3%, p<0.001 and 2.3%, p<0.001, respectively), while black cohosh and placebo did not. Twenty-four out of the 43 women on E2/NETA had an increase in density exceeding 10% and 6 women had an increase of 30% or more. In the tibolone group, only one woman had an increase in density of more than 10%. The difference in increase in breast density between E2/NETA on the one hand and tibolone, black cohosh and placebo on the other was highly significant (p<0.0001). ConclusionsDigitized mammographic breast density is a highly sensitive method confirming significant increase in density by standard E2/NETA treatment and to a lesser extent by tibolone, whereas black cohosh does not influence mammographic breast density during six months treatment. Digitized assessment also yields data on individual variation and small increases left undetectable by visual classification.

What’s in the bottle? Prescriptions formulated by medical herbalists in a clinical trial of treatment during the menopause

This paper reports on the complex prescriptions designed by practitioners of western herbal medicine in a pilot randomised, waiting-list controlled trial carried out in primary care in the UK. Herbal practitioners recorded their prescriptions and advice contemporaneously during the pragmatic trial investigating 5months of treatment for symptoms associated with the menopause. Treatment was modified so that the 35 participants received 141 prescriptions between them during the course of their treatment. These complex prescriptions were shown to contain varying combinations of a total of 80 herbs. Between 4 and 9 herbs were used in each prescription. The three most commonly prescribed herbs were Leonurus cardiaca, Cimicifuga racemosa and Salvia officinalis. Care included not only herbal prescriptions but also dietary and lifestyle advice and discussion of self care in an evolving therapeutic relationship. The care was individually reviewed and adjusted at each consultation over the course of treatment.

Deoxyactein stimulates osteoblast function and inhibits bone‐resorbing mediators in MC3T3‐E1 cells

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. In order to improve the treatment of osteoporosis, identification of anabolic agents with minimal side effects is highly desirable. Cimicifuga racemosa has a long and diverse history of medicinal use and deoxyactein isolated from this species is one of the major constituents. In the present study, the effect of deoxyactein on the function of osteoblastic MC3T3-E1 cells was studied. Deoxyactein caused a significant elevation of cell growth, alkaline phosphatase activity, collagen content, and mineralization in the cells (P < 0.05). Moreover, deoxyactein significantly (P < 0.05) decreased the production of reactive oxygen species (ROS) and osteoclast differentiation-inducing factors such as TNF-α, IL-6 and receptor activator of nuclear factor-κB ligand in the presence of antimycin A, which inhibits mitochondrial electron transport and has been used as an ROS generator. These results demonstrate that deoxyactein may have positive effects on skeletal structure.