Black Cohosh

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Black Cohosh (Actaea racemosa L.): Traditional Medicinal Uses, Side Effects, Contraindications, and Drug Interactions

Introduction

Black cohosh (Actaea racemosa L., syn. Cimicifuga racemosa) is a perennial herb native to deciduous woodlands in eastern North America with an extensive history of traditional medicinal use^[1][2]. The plant's rhizomes and roots have been utilized for centuries by Native Americans and later adopted by European settlers for various therapeutic purposes^[3][4]. Today, black cohosh is one of the most popular herbal dietary supplements worldwide, primarily used for alleviating menopausal symptoms^[5][6]. This comprehensive review  examines the traditional medicinal applications of black cohosh roots and rhizomes, along with scientifically documented side effects, contraindications, and potential drug interactions, providing evidence-based information for healthcare practitioners and consumers.

Botanical Description

Black cohosh is a perennial herb belonging to the Ranunculaceae family that flowers in mid-summer^[1][2]. The plant grows to a height of 1-2.5 meters and features compound leaves, white flowers arranged in tall racemes, and a thick, knotted rhizome system^[2][4]. Native to eastern North America, black cohosh thrives in the understory of deciduous forests, particularly in the Appalachian region^[7][8]. The medicinal parts of the plant are the rhizomes and roots, which are typically harvested in the fall after the plant has flowered and set seed^[4][2].

Bioactive Constituents

Black cohosh contains numerous bioactive compounds that contribute to its medicinal properties:

Triterpene Glycosides

·         Cycloartane glycosides: Including actein, 23-epi-26-deoxyactein, cimigenol, cimiracemoside, and various other derivatives that are considered the primary active constituents^[9][10][11].

·         These compounds are characterized by a cycloartane scaffold and a pentose moiety, with variations in their sugar moieties and substitution patterns affecting their biological activities^[9][4].

Phenolic Compounds

·         Phenolic acids: Including caffeic acid, ferulic acid, isoferulic acid, and fukinolic acid^[12][11][10].

·         Cimicifugic acids: A and B, which have shown strong inhibitory effects on CYP450 enzymes^[13][12].

Other Compounds

·         Flavonoids: Various flavonoid compounds that contribute to the plant's antioxidant properties^[10][11].

·         Serotonin-like compounds: N-methylserotonin and related tryptamine derivatives that may contribute to the serotonergic activities of black cohosh preparations^[14][8].

·         Volatile oils: Small amounts of volatile compounds that contribute to the plant's characteristic odor^[11][10].

Traditional Medicinal Uses

Native American Traditional Medicine

Black cohosh has been utilized for centuries by Native Americans, particularly by tribes in the eastern United States, for various medicinal purposes^[3][1]:

·         Treatment of women's health issues, including menstrual irregularities, labor induction, and menopausal symptoms^[1][4].

·         Relief of rheumatoid arthritis and inflammatory conditions^[12][1].

·         Management of respiratory ailments, including coughs and sore throats^[3][1].

·         Treatment of kidney disorders and as a general tonic^[1][8].

Historical European and American Medicine

Following its adoption by European settlers, black cohosh became incorporated into various medical traditions^[3][2]:

·         Used in the Eclectic medical tradition for gynecological disorders, rheumatism, and as a sedative^[2][1].

·         Employed in the treatment of neurological conditions such as chorea and epilepsy^[1][2].

·         Prescribed for various pain conditions, including headaches and muscular pain^[2][3].

Contemporary Uses

Modern applications of black cohosh primarily focus on women's health issues^[5][6]:

·         Management of menopausal symptoms, particularly hot flashes, night sweats, and sleep disturbances^[5][6].

·         Relief of premenstrual syndrome and menstrual discomfort^[6][1].

·         Support for gynecological health and hormonal balance^[6][5].

·         Potential adjunctive therapy in osteoporosis prevention^[6][9].

Mechanism of Action

The precise mechanisms by which black cohosh exerts its therapeutic effects remain incompletely understood, but several pathways have been proposed based on scientific research^[14][12]:

Neuroendocrine Effects

·         Serotonergic activity: Black cohosh contains N-methylserotonin and other compounds that may interact with serotonin receptors, potentially explaining its effects on thermoregulation and mood^[14][8].

·         Dopaminergic activity: Some studies suggest that black cohosh may act on dopamine receptors, which could contribute to its effects on hormone regulation^[14][12].

Anti-inflammatory Effects

·         Black cohosh contains compounds like cimiracemate A that have demonstrated anti-inflammatory properties by suppressing TNF-alpha production and modulating NF-kappaB activity^[12][9].

·         These effects may explain its traditional use in treating inflammatory conditions such as arthritis^[12][1].

Hormonal Effects

·         Earlier research suggested estrogen-like effects, but more recent studies indicate that black cohosh does not act as a phytoestrogen^[10][6].

·         The plant may influence hormone-regulating mechanisms through other pathways, including effects on the hypothalamic-pituitary axis^[6][14].

Scientific Evidence for Traditional Uses

Menopausal Symptoms

Research on black cohosh for menopausal symptoms has shown mixed results:

·         Several clinical trials have demonstrated efficacy in reducing hot flashes and other menopausal symptoms^[6][5].

·         The European Medicines Agency (EMA) has recognized black cohosh as having sufficient clinical evidence to support its use for menopausal symptom relief^[15][6].

·         Some studies suggest that black cohosh may be as effective as low-dose hormone replacement therapy for certain menopausal symptoms^[6][5].

Anti-inflammatory Effects

Scientific evidence supports some of the traditional anti-inflammatory applications:

·         In vitro studies have demonstrated that black cohosh extracts can inhibit pro-inflammatory cytokines and reduce inflammatory markers^[12][9].

·         The compound cimiracemate A has shown particular promise as an anti-inflammatory agent^[12][9].

Other Traditional Uses

Research on other traditional applications of black cohosh is more limited:

·         Some preliminary studies suggest potential benefits for bone health, which may support its use in osteoporosis prevention^[6][9].

·         Limited evidence exists for its traditional use in treating rheumatism and other pain conditions^[12][1].

Side Effects

Based on published research, black cohosh consumption is associated with several potential side effects:

Mild Side Effects

·         Gastrointestinal disturbances, including nausea, vomiting, and abdominal pain^[5][13].

·         Headaches and dizziness in some individuals^[5][6].

·         Rash and other skin reactions in sensitive individuals^[5][13].

Hepatotoxicity Concerns

·         Numerous case reports have documented liver damage potentially associated with black cohosh use, ranging from mild elevations in liver enzymes to severe hepatitis requiring liver transplantation^[5][13].

·         The causality of these cases has been questioned, as many involved multiple medications or supplements, and the mechanism of potential hepatotoxicity remains unclear^[13][16].

·         Some research suggests that hepatotoxicity may be related to herb-drug interactions rather than direct toxicity^[13][16].

Other Concerns

·         Some studies have reported potential genotoxicity through an aneugenic mode of action, although the clinical significance of this finding is uncertain^[5][16].

·         Paradoxical effects on inflammatory markers have been observed in some studies, particularly with high doses^[5][12].

Contraindications

Based on published research, black cohosh should be used with caution or avoided in the following circumstances:

Pregnancy and Breastfeeding

·         Black cohosh has traditionally been used to stimulate uterine contractions and may potentially affect hormone levels, making it contraindicated during pregnancy^[5][6].

·         Limited safety data exists for black cohosh use during lactation, and it is generally advised to avoid medicinal doses during breastfeeding^[5][6].

Liver Disease

·         Due to concerns about potential hepatotoxicity, black cohosh is contraindicated in individuals with pre-existing liver disease or a history of liver problems^[5][13].

·         Patients taking black cohosh should be monitored for signs of liver dysfunction, such as jaundice, dark urine, or right upper quadrant pain^[13][5].

Hormone-Sensitive Conditions

·         Although the estrogenic activity of black cohosh is debated, caution is advised in individuals with hormone-sensitive conditions such as breast, uterine, or ovarian cancer^[5][6].

·         Some research suggests that certain black cohosh compounds may have cytotoxic effects against breast cancer cells, but clinical implications remain unclear^[9][6].

Neurological Conditions

·         Due to its potential effects on neurotransmitter systems, caution is advised in individuals with seizure disorders or other neurological conditions^[14][5].

·         Patients taking medications that affect serotonin or dopamine pathways should consult healthcare providers before using black cohosh^[14][13].

Drug Interactions

Published research has identified several potential drug interactions with black cohosh:

Cytochrome P450 Enzyme Interactions

·         Black cohosh extracts and specific compounds (particularly fukinolic acid and cimicifugic acids) have demonstrated inhibitory effects on multiple CYP450 enzymes (1A2, 2D6, 2C9, 3A4) in vitro^[13][16].

·         These interactions could potentially alter the metabolism of medications processed by these enzymes, although clinical significance may vary^[13][16].

Anticoagulants and Antiplatelet Drugs

·         Theoretical concerns exist about potential interactions with anticoagulant and antiplatelet medications, although clinical evidence is limited^[13][5].

·         Patients taking warfarin, aspirin, or other blood-thinning medications should use black cohosh with caution and under medical supervision^[5][13].

Hormone Therapies

·         Potential interactions with hormone replacement therapy or hormonal contraceptives have been suggested, although the clinical significance is unclear^[5][6].

·         Concurrent use of black cohosh with hormone therapies should be approached with caution and under healthcare provider guidance^[6][5].

Hepatotoxic Medications

·         Concomitant use of black cohosh with medications known to affect liver function may increase the risk of hepatotoxicity^[13][5].

·         Caution is advised when combining black cohosh with acetaminophen, statins, or other potentially hepatotoxic drugs^[5][13].

Dosage and Administration

Traditional medicinal uses of black cohosh typically involve the following dosage forms and amounts:

Standardized Extracts

·         Commercial preparations are typically standardized to contain 2.5% triterpene glycosides, calculated as 27-deoxyactein^[6][4].

·         Typical dosage ranges from 20-80 mg of standardized extract daily, divided into 1-2 doses^[6][4].

Traditional Preparations

·         Dried rhizome/root: 0.3-2 g daily, typically prepared as a decoction or infusion^[4][6].

·         Tincture (1:10 in 60% ethanol): 0.4-2 mL, 1-3 times daily^[6][4].

Duration of Use

·         For menopausal symptoms, treatment duration of 3-6 months is common, with reassessment of benefits and risks for longer-term use^[6][5].

·         Continuous use beyond 6 months should be monitored by healthcare providers due to limited long-term safety data^[5][6].

Quality and Adulteration Concerns

The quality and authenticity of black cohosh products are significant concerns:

·         Adulteration with Asian Cimicifuga species (such as C. dahurica, C. foetida, and C. heracleifolia) has been reported in commercial products^[10][4].

·         Misidentification and substitution with other plants have led to quality control issues in the marketplace^[4][10].

·         Standardization of products is challenging due to the complex phytochemical profile and variability in growing conditions^[11][4].

Conclusion

Black cohosh (Actaea racemosa L.) has a rich history of traditional medicinal use, particularly for women's health conditions^[1][6]. Contemporary applications focus primarily on the management of menopausal symptoms, for which there is moderate clinical evidence of efficacy^[6][5]. The plant contains a complex array of bioactive compounds, including triterpene glycosides, phenolic acids, and serotonin-like substances, which may contribute to its therapeutic effects through multiple mechanisms^[9][14][11].

While generally considered safe when used appropriately, black cohosh has been associated with potential hepatotoxicity and other adverse effects that warrant caution^[5][13]. Significant drug interactions, particularly with medications metabolized by CYP450 enzymes, are also a concern^[13][16]. Contraindications include pregnancy, pre-existing liver disease, and hormone-sensitive conditions^[5][6].

As with many herbal medicines, quality control and standardization remain challenges in ensuring the safety and efficacy of black cohosh products^[10][4]. Further research is needed to fully elucidate the mechanisms of action, optimize dosing regimens, and establish long-term safety profiles for this important medicinal plant^[1][6].

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1.       https://www.eurekaselect.com/235087/article             

2.       https://www.cropj.com/yang_17_1_2023_83_89.pdf       

3.       https://www.mdpi.com/2305-6320/5/4/121    

4.       https://journals.ashs.org/view/journals/hortsci/42/1/article-p61.xml            

5.       https://www.tandfonline.com/doi/full/10.1080/26896583.2025.2513795                            

6.       https://www.mdpi.com/1424-8247/15/3/278                            

7.       https://bioone.org/journals/the-journal-of-the-torrey-botanical-society/volume-148/issue-2/TORREY-D-20-00026.1/Soil-and-microbe-interactions-in-two-populations-of-Appalachian-black/10.3159/TORREY-D-20-00026.1.full

8.       http://www.scirp.org/journal/doi.aspx?DOI=10.4236/ajps.2015.619319   

9.       https://www.mdpi.com/1420-3049/25/4/766        

10.    https://openpublishing.library.umass.edu/jmap/article/id/1733/       

11.    https://pubs.acs.org/doi/10.1021/jf802481w     

12.    https://pubs.acs.org/doi/10.1021/jm9006164          

13.    http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1574-8863&volume=5&issue=2&spage=118                

14.    https://www.mdpi.com/2223-7747/14/2/292       

15.    https://ptfarm.pl/download/?file=File%2FFarmacja+Polska%2F2024%2F6%2F05_SZ_Pluskwica_groniasta_n.pdf

16.    https://pubs.acs.org/doi/10.1021/tx020108n     

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