black cohosh in women with a history of breast cancer. Results from a 2002 study testing the safety of black cohosh in an in vitro model for oestrogen-dependent breast tumours found that the herbal extract significantly inhibited tumour cell proliferation, oestrogen-induced prolifera- tion and enhanced the antiproliferative effects of tamoxifen (Bodinet & Freudenstein 2002). This finding is supported in a more recent in vitro study that showed black cohosh having a cyto- toxic effect on both oestrogen-sensitive and oestrogen-insensitive breast cancer cells and a synergism with tamoxifen for inhibition of can- cerous cell growth (Al-Akoum et al 2007). A 2013 systematic review of black cohosh in breast cancer found that the current evidence does not demonstrate an increased risk or recurrence of breast cancer in women with or without a history (Fritz et al 2013). As with all medicines, a risk-versus-benefit conversation should take place with patients.
B
supervision by people undergoing chemotherapy, receiving treatment for oestrogen-dependent tumours or during pregnancy.
Due to rare case reports of idiosyncratic hepatic reactions, avoid prescribing black cohosh in con- junction with medications that are potentially hepa- totoxic or in patients with liver disease, until safety can be confirmed.
REFERENCES
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Bai W et al. Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: a randomized, double blind, parallel-controlled study versus tibolone. Maturitas 58.1 (2007): 31–41.
Beck V et al. Comparison of hormonal activity (estrogen, androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy. J Steroid Biochem Mol Biol 84.2–3 (2003): 259–68.
Blumenthal M, Goldberg A, Brinckmann J (eds). Herbal medicine: expanded Commission E monographs. Austin, TX: Integrative Medicine Communications, 2000.
Bodinet C, Freudenstein J. Influence of Cimicifuga racemosa on the proliferation of estrogen receptor-positive human breast cancer cells. Breast Cancer Res Treat 76.1 (2002): 1–10.
Bolle P et al. Estrogen-like effect of a Cimicifuga racemosa extract sub-fraction as assessed by in vivo, ex vivo and in vitro assays. J Steroid Biochem Mol Biol 107.3–5 (2007): 262–269.
Borrelli F, Ernst E. Black cohosh (Cimicifuga racemosa) for menopausal symptoms: a systematic review of its efficacy. Pharmacol Res 58.1 (2008): 8–14.
Briese V et al. Black cohosh with or without St. John’s wort for symptom-specific climacteric treatment — results of a large-scale, controlled, observational study. Maturitas 57.4 (2007): 405–414. Burdette JE et al. Black cohosh acts as a mixed competitive ligand and
partial agonist of the serotonin receptor. J Agric Food Chem 51.19 (2003): 5661–5670.
Burke BE, Olson RD, Cusack BJ. Randomized, controlled trial of phytoestrogen in the prophylactic treatment of menstrual migraine. Biomed Pharmacother 56.6 (2002): 283–288.
Chan BY et al. Ethanolic extract of Actaea racemosa (black cohosh) potentiates bone nodule formation in MC3T3-E1 preosteoblast cells. Bone 43.3 (2008): 567–573.
Cheema D, Coomarasamy A, El-Toukhy T. Non-hormonal therapy of post-menopausal vasomotor symptoms: a structured evidence-based review. Arch Gynecol Obstet 276.5 (2007): 463–469.
Chung DJ et al. Black cohosh and St. John’s wort (GYNO-Plus) for climacteric symptoms. Yonsei Med J 48.2 (2007): 289–294. Drewe J, Zimmermann C, Zahner C. The effect of a Cimicifuga
racemosa extracts Ze 450 in the treatment of climacteric complaints — an observational study. Phytomedicine, 20.8–9 (2013): 659–666. Dugoua JJ et al. Safety and efficacy of black cohosh (Cimicifuga
racemosa) during pregnancy and lactation. Can J Clin Pharmacol 13.3 (2006): e257–261.
Duker EM et al. Effects of extracts from Cimicifuga racemosa on gonadotropin release in menopausal women and ovariectomized rats. Planta Med 57.5 (1991): 420–424.
Einbond LS et al. Actein and a fraction of black cohosh potentiate antiproliferative effects of chemotherapy agents on human breast cancer cells. Planta Med 72.13 (2006): 1200–1206.
Einbond LS et al. The growth inhibitory effect of actein on human breast cancer cells is associated with activation of stress response pathways. Int J Cancer 121.9 (2007): 2073–2083.
Einbond LS et al. Growth inhibitory activity of extracts and compounds from Cimicifuga species on human breast cancer cells. Phytomedicine 15.6–7 (2008): 504–511.
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Geller SE, Studee L. Botanical and dietary supplements for mood and anxiety in menopausal women. Menopause 14.3 (Pt 1) (2007): 541–549.
Geller SE et al. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause 16.6 (2009): 1156–1166.
PATIENTS’ FAQs
What will this herb do for me?
Black cohosh may be an effective treatment for menopausal symptoms in most women, especially those with mild to moderate symptoms. The Euro- pean extracts give the most consistently positive results for reducing the frequency of hot flushes. Effects are also good when combined with the herb St John’s wort. It may also be useful in the treat- ment of premenstrual syndrome and prevention of period cramping. Black cohosh can also be consid- ered in women with unexplained or PCOS-related infertility.
When will it start to work?
Studies suggest that benefits are seen within 4–12 weeks for the treatment of menopausal symptoms.
Are there any safety issues?
Black cohosh is well tolerated with few side effects. It should only be used under professional
Practice points/Patient counselling
• In general, clinical trials support the use of black cohosh for relieving menopausal symp- toms, with most consistent benefits reported for the European extracts.
• It appears that 4–12 weeks continuous treat- ment are required for adequate menopausal symptom relief and it can be used successfully with St John’s wort.
• Black cohosh is also used in the treatment of premenstrual syndrome and dysmenorrhoea and is Commission E-approved for these uses; however, controlled studies are not available to confirm its efficacy.
• Black cohosh has many different actions, including selective oestrogen receptor modula- tor activity, serotonergic, dopaminergic, anti- inflammatory and analgesic activity.
• Black cohosh should be used only under pro- fessional supervision by people with oestrogen- dependent tumours, or during pregnancy. • Black cohosh is well tolerated with few side
effects; however, rare case reports of idiosyn- cratic hepatic reactions have been described. Until safety can be confirmed, avoid prescrib- ing black cohosh in conjunction with medica- tions that are potentially hepatotoxic or in patients with liver disease.
PREGNANCY USE
Although it has been used to assist in child- birth, black cohosh is not traditionally recom- mended in pregnancy, particularly during the first trimester although it has been used in the final weeks of pregnancy to aid in delivery. Safety in lactation remains to be confirmed; however, it is usually avoided because of its hor- monal effects (Dugoua et al 2006).
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osteoclastogenesis by modulating RANKL and TNFalpha signaling pathways. Chem Biol 14.7 (2007): 860–869.
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cohosh extract (Actaea or Cimicifuga racemosa extract) CR BNO 1055. Menopause 13.4 (2006): 678–691.
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B
Brahmi
HISTORICAL NOTE Brahmi is the Sanskrit name for the herb Bacopa monniera and has been used in Ayurvedic medicine as a nerve tonic since time immemorial. Under this system, B. monniera is classified under ‘Medhya rasayana’, that is, medicinal plants rejuvenating intellect and memory, and has been used in India for almost 3000 years. The ancient classical Ayurvedic treatises recommend it for the promotion of memory, intelligence and general performance. Over time, it has earned a reputation as an important brain tonic (Williamson 2002).
COMMON NAME
Brahmi
OTHER NAMES
Bacopa, herb of grace, herpestis herb, Indian pen- nywort, jalanimba, jalnaveri, sambrani chettu, thyme-leave gratiola, keenmind, Nira-Brahmi, Sam- brani Chettu
Centella asiatica (gotu kola) and Merremia gangetica
have also been referred to by the name brahmi, but most authorities associate brahmi with Bacopa mon-
niera. The name brahmi is derived from the word
‘Brama’, the mythical ‘creator’ in the Hindu pan- theon. Because the brain is the centre for creative activity, any compound that improves brain health is called brahmi (Russo & Borrelli 2005).
BOTANICAL NAME/FAMILY
Bacopa monniera (family Scrophulariaceae)
PLANT PARTS USED
Dried whole plant or herb, mainly leaves and stems (aerial parts)
CHEMICAL COMPONENTS
Dammarene-type saponins (bacosides [A, B, C] and bacosaponines [D, E, F], based on the bacogenins A1–A5, are considered the most important) and alkaloids (brahmine, herpestine), flavonoids (luteolin-7-glucoside, glucuronyl-7-apigenin and glucuronyl-7-luteolin), phytosterols (Chakravarty et al 2003) and luteolin, phenylethanoid glycosides,
monnierasides I–III and plantainoside B have been isolated (Adams et al 2007).
Standardised extract BacoMind has been shown to contain bacoside A3, bacopaside I, bacopaside II, jujubogenin isomer of bacopasaponin C, bacosine, luteolin, apigenin and β-sitosterol d-glucoside (Dutta et al 2008).
The commercial extract KeenMind is stan- dardised for bacosides A and B (no less than 55% of combined bacosides). Each capsule contains 150 mg
B. monniera extract (20 : 1), equivalent to 3 g dried
herb.
MAIN ACTIONS
Information about the mechanisms of action of brahmi chiefly comes from in vitro and animal tests using various experimental models, although an increasing number of clinical trials are now avail- able. Some studies have investigated the effects of an Ayurvedic herbal combination known as brahmi rasayan, which consists of 10 parts bacopa, two parts cloves, one part cardamom, one part Piper longum and 40 parts sucrose.
Antioxidant
Brahmi has potent antioxidant activity, which appears to be a result of both direct free radical scavenging activity and increasing the activity of endogenous antioxidant systems (Bhattacharya et al 2000, Tripathi et al 1996). Administration of bacoside A reduced the effects of cigarette smoke in an animal model by increasing lactate
Cognitive or nootropic effects — multiple mechanisms
Cognitive and nootropic effects are not merely due to antioxidant activity and neuroprotection, as dem- onstrated in an experimental model of Alzheimer’s dementia whereby the cognitive-enhancing effect of
Bacopa monniera was not well correlated with its
neuroprotection (Uabundit et al 2010).
Evidence shows that cognitive activation is due to a combination of mechanisms, which include serotonergic and cholinergic systems together with antioxidant and mitochondrial stabilisation activities. Further research with experimental models indicates that bacopa enhances synaptic plasticity (Preethi et al 2012). The saponins bacoside A and B are considered to be the most important active constitu- ents responsible for enhancing cognitive function (Russo & Borelli 2005, Singh & Dhawan 1982).
Effects on the cholinergic system include the modulation of acetylcholine release, choline acety- lase activity and muscarinic cholinergic receptor binding (Das et al 2002). Results from a double- blind, placebo-controlled trial using brahmi (300 mg/day) support this view, as one of the major effects seen was on speed of early information pro- cessing, a function predominantly modulated by the cholinergic system (Stough et al 2001). Bacopa
monniera (120 mg/kg oral) significantly reversed
diazepam-induced (1.75 mg/kg intraperitoneal) amnesia in an animal study (Saraf et al 2008), thereby confirming previous reports of cholinergic activity (Dhanasekaran et al 2007).
Research in animal models provides evidence of activation of the serotonergic system (Charles et al 2011). In one study, the level of serotonin (5-HT) increased in rat brains while dopamine decreased significantly. Based on this observation, the learning and memory enhancement effects are likely to be due to upregulation of serotonin-synthesising enzyme tryptophan hydroxylase-2 expression which could enhance 5-HT synthesis and also upregulated SERT (serotonin transporter) expression, which would enhance transportation of 5-HT and subse- quent activation of the 5-HT3A receptor during hippocampus-dependent learning. The characterised
Bacopa monniera leaf extract used in this study
contained 31.27% bacosides, i.e. bacopaside I (0.9%), bacoside A3 (9.47%), bacopaside II (17.15%), jujubogenin of bacopasaponin C (0.38%) and baco- pasaponin C (3.37%). High-performance liquid chromatography analysis confirmed the presence of bioactive compounds in the serum of treated rats.