Cohosh, Blue

C

Summary and Pharmaceutical Comment

Limited data are available on the chemistry of blue cohosh. Documented pharmacological actions support some of the reputed traditional uses, although many of these are not suitable indications for self-medication. No evidence regarding antirheumatic properties was located, although anti-inflammatory action has been documented for the aerial plant parts. In view of the potential toxicity associated with blue cohosh, it should be used with caution. The potential for preparations of blue cohosh to interfere with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered. The use of blue cohosh preparations during pregnancy and breastfeeding should be avoided.

Species (Family)

Caulophyllum thalictroides (L.) Mich. (Berberidaceae)

Synonym(s)

Caulophyllum, Leontice thalictroides L., Papoose Root, Squaw Root

Part(s) Used

Rhizome, root

Pharmacopoeial and Other Monographs

BHP 1983(G7)

Martindale 35th edition(G85)

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General References G22, G41 and G48.

Alkaloids Quinolizidine and isoquinoline-types. Anagyrine, baptifoline, magnoflorine, methylcytisine (caulophylline). Other unidentified minor tertiary alkaloids.(1)

Saponins Caulosaponin and cauloside D yielding hederagenin on hydrolysis.(2)

Other constituents Citrullol, gum, resins, phosphoric acid, phytosterol and starch.

Other Caulophyllum species A related species, C. robustum Maxim., is rich in triterpene glycosides (caulosides A–G), most of which possess hederagenin as their aglycone.

Food Use

Blue cohosh is not used in foods.

Herbal Use

Blue cohosh is stated to possess antispasmodic, emmenagogue, uterine tonic and antirheumatic properties. Traditionally, it has been used for amenorrhoea, threatened miscarriage, false labour pains, dysmenorrhoea, rheumatic pains, and specifically for conditions associated with uterine atony.(G7, G64)

Dosage

Dosages for oral administration (adults) for traditional uses recommended in standard herbal reference texts are given below.

Dried rhizome/root 0.3–1.0 g as a decoction three times daily.(G7)

Liquid extract 0.5–1.0 mL (1 : 1 in 70% alcohol) three times daily.(G7)

Pharmacological Actions

In vitro and animal studies

A blue cohosh extract exhibited stimulant properties on the isolated guinea-pig uterus, although subsequent in vivo studies in cats, dogs and rabbits demonstrated no uterine activity.(3)

Figure 1 Selected constituents of blue cohosh.

Antifertility actions documented in rats were reported to be caused by inhibition of ovulation(4) and by interruption of implantation.(5)

Smooth muscle stimulation has been documented for a crystalline glycoside constituent on the uterus (in vitro), the small intestine (in vitro), and the coronary blood vessels (in vivo) of various small mammals.(6) The glycoside was also reported to cause erythrolysis and to be of an irritant nature. An earlier study that used a crystalline glycoside identified as caulosaponin, reported a variety of actions including an oxytocic effect on the isolated rat uterus, constriction of coronary and carotid blood vessels, a toxic action on cardiac muscle, and a spasmogenic action on the isolated intestine.(6)

Methylcytisine is stated to have a nicotinic-like action, causing an elevation in blood pressure and stimulating both respiration and intestinal motility.(G60)

Figure 2 Blue cohosh (Caulophyllum thalictroides).

Figure 3 Blue cohosh – dried drug substance (root).

There is a lack of clinical safety and toxicity data for blue cohosh and further investigation of these aspects is required.

Powdered blue cohosh is stated to be irritant, especially to mucous membranes.(G51) The leaves and seeds are reported to

contain methylcytisine and some glycosides that can cause severe stomach pains. Children have been poisoned by eating the bright blue bitter-tasting seeds.(G22) Caulosaponin is reported to be cardiotoxic, causing constriction of coronary blood vessels, to produce intestinal spasms, and to possess oxytocic properties.(G60)

There is an isolated report of tachycardia, diaphoresis, muscle weakness and fasciculations in a 21-year-old woman who ingested blue cohosh tincture in an attempt to induce an abortion. The woman's symptoms, which resolved over the following 24 hours, were considered to be consistent with those of nicotine toxicity.(8)

Preclinical data

N-methylcytisine isolated from blue cohosh root material demonstrated teratogenic activity in rat embryo culture, an invitro system used to detect potential teratogens.(9) The clinical significance of this finding has not been established.

Contra-indications, Warnings

Blue cohosh may irritate gastrointestinal conditions. It is not known whether excessive doses of blue cohosh may cause a rise in blood pressure, because of the methylcytisine content.

Drug interactions None documented. However, in view of the limited information on the chemistry of blue cohosh, and documented pharmacological actions, the potential for preparations of blue cohosh to interfere with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered.

Pregnancy and lactation There are insufficient data on the use of blue cohosh preparations during pregnancy and breastfeeding, and the use of blue cohosh should be avoided during these periods.

Blue cohosh is reputed to be an abortifacient and to affect the menstrual cycle.(G30)

Preparations

Proprietary multi-ingredient preparations

Australia: Dyzco; Lifesystem Herbal Formula 4 Women's Formula; Women's Formula Herbal Formula 3.

182 Cohosh, Blue

References

Caulophyllum on implantation in rats. J Reprod Fertil 1974; 38: 245– 246.

6 Ferguson HC, Edwards LD. A pharmacological study of a crystalline glycoside of Caulophyllum thalictroides. J Am Pharm Assoc 1954; 43: 16–21.

7 Benoit PS et al. Biological and phytochemical evaluation of plants XIV. Anti-inflammatory evaluation of 163 species of plants. Lloydia 1976; 393: 160–171.

8Rao RB, Hoffman RS. Nicotinic toxicity from tincture of blue cohosh (Caulophyllum thalictroides) used as an abortifacient. Vet Hum Toxicol 2002; 44: 221–222.

9Kennelly EJ et al. Detecting potential teratogenic alkaloids from blue cohosh rhizomes using an in vitro rat embryo culture. J Nat Prod 1999; 62: 1385–1389.

Summary and Pharmaceutical Comment

The principal active constituent in cola is caffeine. The reputed herbal uses of cola can be attributed to the actions of caffeine, and precautions associated with other xanthinecontaining beverages are applicable to cola.

Species (Family)

Cola nitida (Vent.) Schott & Endl. (Sterculiaceae) *Cola acuminata (P. Beauv.) Schott & Endl.

Synonym(s)

Cola Seed, Guru Nut, Kola Nut *Sterculia acuminata Beauv.

Part(s) Used

Cotyledon

Pharmacopoeial and Other Monographs

BHC 1992(G6)

BHP 1996(G9)

BP 2007(G84)

Complete German Commission E(G3)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General References G6 and G62.

Alkaloids Xanthine-types. Caffeine (0.6–3.0%), theobromine (up to 0.1%).

Tannins Condensed type, catechins.

Other constituents Betaine, cellulose, enzyme, fats, a glucoside, protein, red pigment and sugars.

Figure 1 Selected constituents of cola.

C

Food Use

Cola is listed by the Council of Europe as a natural source of food

flavouring (cola and cola nut extract: category N4, with limits on caffeine) (see Appendix 3).(G17) Cola is commonly used in foods.

Previously, cola has been listed as GRAS (Generally Recognised As Safe).(G41)

Herbal Use

Cola is stated to possess CNS stimulant, thymoleptic, antidepressant, diuretic, cardioactive and antidiarrhoeal properties. It has been used for depressive states, melancholy, atony, exhaustion, dysentery, atonic diarrhoea, anorexia, migraine and specifically

for depressive states associated with general muscular weak-

ness.(G6, G7, G8, G64)

Dosage

Dosages for oral administration (adults) for traditional uses recommended in older standard herbal and pharmaceutical reference texts are given below.

Figure 2 Cola (Cola nitida).

Figure 3 Cola – dried drug substance (cotyledon).

184 Cola

Powdered cotyledons 1–3 g as a decoction three times daily.(G6,

G7)

Liquid Extract of cola (BPC 1949) 0.6–1.2 mL (1 : 1 in 60% alcohol).

CTincture of cola (BPC 1934) 1–4 mL (1 : 5 in 60% alcohol).

Pharmacological Actions

The xanthine constituents, caffeine and theobromine, are the active principles in cola. The pharmacological properties of caffeine are well documented and include stimulation of the CNS,

respiratory system and skeletal muscle, cardiac stimulation, coronary dilatation, smooth muscle relaxation and diuresis.(G41)

Cola-containing beverages are stated to provide active doses of caffeine.(G45)

Side-effects, Toxicity

Side-effects commonly associated with xanthine-containing bev-

erages include sleeplessness, anxiety, tremor, palpitations and withdrawal headache.(G54)

Contra-indications, Warnings

Consumption of cola should be restricted in individuals with hypertension or cardiac disorders, because of the caffeine content.

Drug interactions None documented. However, the potential for preparations of cola to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered.

Pregnancy and lactation It is generally recommended that caffeine consumption should be restricted during pregnancy, although conflicting reports have been documented regarding the association between birth defects and caffeine consumption. In view of this, excessive consumption of cola during pregnancy should be avoided. Caffeine is excreted in breast milk, but at concentrations considered too low to represent a hazard to breastfed infants.(G45) However, as with all xanthine-containing beverages, excessive consumption of cola by lactating mothers should be avoided.