Pulsatilla

Summary and Pharmaceutical Comment

Pulsatilla is widely used in both herbal and homeopathic preparations, although little documented chemical and pharmacological information is available to assess its effects. There is a lack of robust clinical research assessing the efficacy and safety of pulsatilla. The fresh plant is known to be irritant; it contains a toxic principle (protoanemonin) and should not be ingested. The dried plant material is not considered to be toxic, but allergic reactions have been documented. In view of this and the lack of safety information, the use of pulsatilla during pregnancy and lactation should be avoided.

Species (Family)

*Pulsatilla vulgaris Mill. (Ranunculaceae)

†Pulsatilla pratensis (L.) Mill.

‡Pulsatilla patens (L.) Mill.

Synonym(s)

*Anemone pulsatilla L., Pulsatilla ucrainica (Ugr.) E.D. Wissjul, Pasque Flower

†Anemone pratensis L., Pulsatilla nigricans Störck, Small Pasque Flower

‡Anemone patens (L.) Mill.

Part(s) Used

Herb

Pharmacopoeial and Other Monographs

BHC 1992(G6)

BHP 1996(G9)

Martindale 35th edition(G85)

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General Reference G6.

Flavonoids Delphinidin and pelargonidin glycosides.

Saponins Hederagenin (as the aglycone).

Volatile oils Ranunculin (a glycoside); enzymatic hydrolysis yields the unstable lactone protoanemonin which readily dimerises to anemonin.

Other constituents Carbohydrates (e.g. arabinose, fructose, galactose, glucose, rhamnose), triterpenes (e.g. b-amyrin) and b- sitosterol.

Food Use

Pulsatilla is not used in foods.

Herbal Use

490 Pulsatilla

Figure 2 Pulsatilla (Pulsatilla vulgaris).

Figure 3 Pulsatilla – dried drug substance (herb).

Dosage

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

Dried herb 0.12–0.3 g as an infusion or decoction three times

daily.(G6, G7)

Liquid extract 0.12–0.3 mL (1 : 1 in 25% alcohol) three times

daily.(G6, G7)

Tincture 0.3–1.0 mL (1 : 10 in 40% alcohol) three times daily.(G6,

G7)

Pharmacological Actions

In vitro and animal studies

Utero-activity (stimulant and depressant) has been documented for pulsatilla.(1, 2, G30) In vivo sedative and antipyretic properties in

rodents have been documented for anemonin and protoanemonin.(3)

Cytotoxicity (KB tumour system) has been reported for anemonin.(G22)

Clinical studies

There is a lack of clinical research assessing the effects of pulsatilla and rigorous randomised clinical trials are required.

Side-effects, Toxicity

Clinical data

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

Fresh pulsatilla is poisonous because of the toxic volatile oil component, protoanemonin. Protoanemonin rapidly degrades to

the non-toxic anemonin. Inhalation of vapour from the volatile oil may cause irritation of the nasal mucosa and conjunctiva.(G51)

Allergic reactions to pulsatilla have been documented and patch

tests have produced vesicular reactions with hyperpigmenta- tion.(G51)

Preclinical data

Cytotoxicity has been documented for anemonin (see Pharmacological Actions, In vitro and animal studies).

Contra-indications, Warnings

Fresh pulsatilla is poisonous and should not be ingested. External contact with the fresh plant should be avoided. The toxic principle, protoanemonin, rapidly degrades to the non-toxic anemonin during drying of the plant material. Individuals may experience an allergic reaction to pulsatilla, especially those with an existing hypersensitivity.

Drug interactions None documented. However, the potential for preparations of pulsatilla to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered. There is limited evidence from preclinical studies that certain constituents of pulsatilla (e.g. anemonin) have sedative activity. The clinical relevance of this is not known.

Pregnancy and lactation Pulsatilla is reputed to affect the menstrual cycle.(G22) Utero-activity has been documented for pulsatilla (see Pharmacological Actions, In vitro and animal studies). In view of this, the use of pulsatilla during pregnancy and lactation should be avoided.

Preparations

Proprietary multi-ingredient preparations

Australia: Bioglan Cirflo; Calmo; Lifesystem Herbal Formula 4 Women's Formula; Proflo; Women's Formula Herbal Formula 3. Brazil: Eviprostat. Czech Republic: Cicaderma. France:

Hepatoum; Histo-Fluine P. Germany: Eviprostat N. Japan: Eviprostat. South Africa: Cough Elixir. Singapore: Eviprostat. UK: Anased; Calmanite Tablets; Fenneherb Prementaid; Menopause Relief; Napiers Back Ache Tea; Napiers Monthly Calm Tea; Nytol Herbal; Period Pain Relief; Prementaid; Roberts Alchemilla Compound Tablets. USA: Eye Support Formula.

References

1Pilcher JM et al. The action of the so-called female remedies on the excised uterus of the guinea-pig. Arch Intern Med 1916; 18: 557–583.

2Pilcher JM et al. The action of 'female remedies' on intact uteri of animals. Surg Gynecol Obstet 1918; 18: 97–99.

3Martin ML et al. Pharmacological effects of lactones isolated from

Pulsatilla alpina subsp. apiifolia. J Ethnopharmacol 1988; 24: 185– 191.

Summary and Pharmaceutical Comment

The chemistry of quassia is well-studied and is characterised by bitter terpenoids (quassinoids) and b-carboline indole alkaloids. Limited data have been documented to justify the traditional herbal uses although the bitter principles support the use of quassia as an appetite stimulant in anorexia. However, there is a lack of robust clinical research assessing the efficacy and safety of quassia. In view of the documented cytotoxic activities and limited toxicological data, quassia should not be taken in amounts greatly exceeding those used in foods. The use of quassia during pregnancy and lactation should be avoided.

Species (Family)

*Picrasma excelsa (Sw.) Planch. (Simaroubaceae)

†Quassia amara L.

Synonym(s)

Bitterwood, Picrasma

*Aeschrion excelsa (Sw.) Kuntze, Jamaican Quassia, Quassia excelsa Sw., Simarouba excelsa (Sw.) DC.

†Surinam Quassia

Part(s) Used

Stem wood

Pharmacopoeial and Other Monographs

BHC 1992(G6)

BHP 1996(G9)

Martindale 35th edition(G85)

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General References G2 and G6.

Alkaloids Indole-type. Canthin-6-one, 5-methoxycanthin-6-one,

4-methoxy-5-hydroxycanthin-6-one, N-methoxy-1-vinyl-b-carbo-

line.(1, 2)

Terpenoids Isoquassin (picrasmin) in P. excelsa, quassin 0.2%, quassinol, quassimarin,(3) 18-hydroxyquassin, neoquassin, a dihydronorneoquassin(4) and simalikalactone D in Q. amara.

Coumarins Scopoletin.(1)

Other constituents b-Sitosterol, b-sitostenone; thiamine 1.8% (in P. excelsa).

Food Use

Quassia is listed by the Council of Europe as a natural source of food flavouring (category N2). This category indicates that

quassia can be added to foodstuffs in small quantities, although the concentration of quassin must not exceed 5 mg/kg; a concentration of 50 mg/kg is permitted in alcoholic beverages and 10 mg/kg in pastilles and lozenges.(G16) Previously, quassia has been regarded by the Food and Drugs Administration (FDA) as GRAS (Generally Regarded As Safe).

Herbal Use

Quassia is stated to possess bitter, orexigenic, sialogogue, gastric stimulant and anthelmintic properties. Traditionally, it has been used for anorexia, dyspepsia, nematode infestation (by oral or rectal administration), pediculosis (by topical application), and

specifically for atonic dyspepsia with loss of appetite.(G2, G6, G7,

G8, G64)

Dosage

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

Figure 2 Quassia (Picrasma excelsa).

Dried wood 0.3–0.6 g by cold infusion three times daily.(G6, G7)

Concentrated Quassia Infusion (BPC 1959) 2–4 mL. Quassia Infusion is prepared by diluting one volume of Concentrated Quassia Infusion to eight volumes with water.

Tincture of Quassia (BP 1948) 2–4 mL.

Enema 150 mL per rectum (infusion with cold water, 1 in 20) on three successive mornings together with 16 g magnesium sulfate by mouth.

Pharmacological Actions

In vitro and animal studies

The b-carboline alkaloids have exhibited positive inotropic activity in vitro.(1) Canthin-6-one is reported to possess antibacterial and antifungal activity. Cytotoxic and amoebicidal activities (assessed against guinea-pig keratinocyte and Enta-

moeba histolytica test systems, respectively) have been documented for canthin-6-one and quassin (P. excelsa).(5) However, later

Qstudies have disputed any amoebicidal action. Quassin is reported to be inactive against P388 leukaemia and 9KB test systems. Significant antitumour activity in mice against the P388 lymphatic

leukaemia and in vitro against human carcinoma of the nasopharynx (KB) has been documented.(3) Quassimarin and simalikalactone were both isolated from the active extract.

Clinical studies

There is a lack of clinical research assessing the effects of quassia and rigorous randomised controlled clinical trials are required.

The effective treatment of 454 patients with headlice has been documented for quassia tincture.(6) Quassia has been used as an enema to expel threadworms.(G44)

Side-effects, Toxicity

Clinical data

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

No side-effects have been reported in 454 patients who used quassia tincture as a scalp lotion to treat headlice.(6) Large doses of quassia may irritate the stomach and cause vomiting.(G6)

Figure 3 Quassia – dried drug substance (stem wood).

Contra-indications, Warnings

Large doses of quassia are emetic.

Drug interactions None documented. However, the potential for preparations of quassia to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered. There is limited evidence from preclinical studies that certain constituents of quassia have cardiac effects, however, the clinical relevance of this is not clear. Coumarin constituents detected so far in quassia do not possess the minimum structural requirements for anticoagulant activity.

Pregnancy and lactation In view of the reported cytotoxic and emetic activities, the use of quassia during pregnancy and lactation should be avoided.

Preparations

Proprietary single-ingredient preparations

Argentina: Cuassicum Prevent 2 en 1.

Proprietary multi-ingredient preparations

Argentina: Cuassicum; Uze Active; Yalu. France: Quintonine. Italy: Dekar 2. South Africa: Essens Amara of Groen Amara; Versterkdruppels. Switzerland: Stomacine. UK: Sanderson's Throat Specific.

References

1Wagner H et al. New constituents of Picrasma excelsa, I. Planta Med 1979; 36: 113–118.

2 Wagner H, Nestler T. N-Methoxy-1-vinyl-b-carbolin, ein neues Alkaloid aus Picrasma excelsa (Swartz) Planchon. Tetrahedron Lett

1978; 31: 2777–2778.

3 Kupchan SM, Streelman DR. Quassimarin, a new antileukemic quassinoid from Quassia amara. J Org Chem 1976; 41: 3481–3482.

4Grandolini G et al. A new neoquassin derivative from Quassia amara. Phytochemistry 1987; 26: 3085–3087.

5Harris A, Phillipson JD. Cytotoxic and amoebicidal compounds from

Picrasma excelsa (Jamaican Quassia). J Pharm Pharmacol 1982; 34:

43P.

6Jensen O et al. Pediculosis capitis treated with quassia tincture. Acta Dermat Venereol (Stockholm) 1978; 58: 557–559.