Vervain

Summary and Pharmaceutical Comment

Limited chemical, pharmacological and toxicity data are available for vervain. Documented scientific information does not justifiy the herbal uses. In view of the lack of data on pharmacological effects, efficacy and safety, the appropriateness of medicinal use of vervain should be considered. Excessive use, at least, should be avoided. Vervain should not be used during pregnancy and breastfeeding. The potential for vervain preparations to interact with other medicines should be considered.

Species (Family)

Verbena officinalis L. (Verbenaceae)

Synonym(s)

Verbena

Part(s) Used

Herb

Pharmacopoeial and Other Monographs

BHP 1996(G9)

Martindale 35th edition(G85)

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General Reference G2.

Glycosides Iridoid glycosides: hastatoside, verbenalin (verbanaloside), verbenin (aucubin). Phenylpropanoid glycosides: acteoside (verbascoside) and eukovoside.(1, 2)

Volatile oils Monoterpene components include citral, geraniol, limonene and verbenone.

Other constituents Adenosibe, alkaloid (unspecified), bitters, carbohydrates (stachyose, mucilage), b-carotene, invertin (sucrose hydrolytic enzymes), saponin and tannic acid.

Food Use

Vervain is listed by the Council of Europe as a natural source of food flavouring (category N2). This category indicates that vervain can be added to foodstuffs in small quantities, with a possible limitation of an active principle (as yet unspecified) in the final product.(G16) Previously, vervain was listed by the United

States of America Food and Drugs Administration (FDA) as a Herb of Undefined Safety.(G22)

Figure 1 Selected constituents of vervain.

Herbal Use

Vervain is stated to possess sedative, thymoleptic, antispasmodic, mild diaphoretic and, reputedly, galactogogue properties. Traditionally, it has been used for depression, melancholia, hysteria, generalised seizures, cholecystalgia, jaundice, early stages of fever, and specifically for depression and debility of convalescence after fevers, especially influenza.(G2, G7, G64)

V

Figure 2 Vervain (Verbena officinalis).

592 Vervain

Figure 3 Vervain – dried drug substance (herb).

Dosage

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

Dried herb 2–4 g as an infusion three times daily.(G7)

Liquid extract 2–4 mL (1 : 1 in 25% alcohol) three times daily.(G7)

Tincture 5–10 mL (1 : 1 in 40% alcohol) three times daily.(G7)

Pharmacological Actions

In vitro and animal studies

Chloroform, methanol and petroleum ether extracts of the aerial parts of vervain have anti-inflammatory activity in vivo as determined using the carrageenan-induced paw oedema model.(3) The chloroform extract was found to exhibit the greatest activity. Vervain is stated to have several properties, including galactogogue activity and luteinising activity,(4) although the scientific basis for these statements is not clear.

Verbenalin has been reported to exhibit uterine stimulant activity.(G30) A slight laxative action in mice has been documented for iridoid glycosides.(5)

A total aqueous extract of the aerial parts of the related species Vervain hastata was found to have sedative properties in experiments involving male rats.(6)

Clinical studies

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

Side-effects, Toxicity

Clinical data

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

Preclinical data

It is stated that, in frogs, small doses of verbenalin stimulate the uterus and that high doses paralyse the CNS, following stupor and convulsions,(G22) although the scientific basis for these statements is not known.

Contra-indications, Warnings

None documented.

Drug interactions None documented. In view of the lack of information on the constituents of vervain and their pharmacological activities, the potential for preparations of vervain to interact with other medicines taken concurrently should be considered.

Pregnancy and lactation Vervain is reputed to act as an abortifacient and oxytocic agent(G30) with in vivo utero-activity

documented (see In vitro and animal studies). In view of this, vervain should not be taken during pregnancy.

Vervain is stated to act as a galactogogue,(3) although the scientific basis for this statement is not known. In view of the lack of information on the safety of vervain during breastfeeding, use should be avoided during this period.

Preparations

Proprietary multi-ingredient preparations

Australia: Avena Complex; Calmo; Nevaton. Austria: Sinupret. Czech Republic: Sinupret; Stomatosan. France: Calmophytum; Vigilia. Germany: Sinupret. Hong Kong: Sinupret. Hungary: Sinupret. Italy: Neoderma 47. Russia: Sinupret (Синупрет). Singapore: Sinupret. Switzerland: Sinupret; Tisane pour nourissons et enfants. Thailand: Sinupret. UK: Athera; Fenneherb Prementaid; HRI Night; Kalms Sleep; Modern Herbals Menopause; Modern Herbals Stress; Napiers Sleep Tablets; Newrelax; Period Pain Relief; Prementaid; Roberts Alchemilla Compound Tablets; Scullcap & Gentian Tablets; Stressless; SuNerven.

References

1 Lahloub MF et al. Phenylpropanoid and iridoid glycosides from the Egyptian Verbena officinalis. Planta Med 1986; 52: 47.

2Andary C et al. Structures of verbascoside and orobanchoside, caffeic acid sugar esters from Orobanche rapum-genistae. Phytochemistry

1982; 21: 1123–1127.

3Deepak M, Handa SS. Antiinflammatory activity and chemical composition of extracts of Verbena officinalis. Phytotherapy Res 2000;

14(6): 463–465.

4Oliver-Bever BEP. Medicinal Plants in Tropical West Africa. Cambridge: Cambridge University Press, 1986.

5 Inouye H et al. Purgative activities of iridoid glycosides. Planta Med 1974; 25: 285–288.

6Akanmu HA et al.. Hypnotic effects of total aqueous extracts of

Vervain hastata. Psychiatry Clin Neurosci 2002; 56(3): 309–310.

Summary and Pharmaceutical Comment

Phytochemical studies documented for wild carrot concentrate on the composition of the volatile oil obtained from both the fresh and dried fruits (seeds). The composition of the oil varies between different cultivars. Preclinical studies have documented a variety of pharmacological actions including CNS-depressant, spasmodic and antispasmodic, hypotensive and cardiac-depressant activities. However, there is a lack of robust clinical research assessing the efficacy and safety of wild carrot. The principal traditional use of wild carrot is as a diuretic. This activity has not been documented in animal studies, but the seed oil of wild carrot does contain terpinen-4-ol, the diuretic principle documented for juniper. Toxicity data only refer to the oil and indicate low toxicity. In view of the limited information on safety, excessive use of wild carrot and use during pregnancy and lactation should be avoided.

Species (Family)

Daucus carota L. subsp. carota (Apiaceae/Umbelliferae)

Synonym(s)

Daucus, Daucus carota L. subsp. maximus auct. lusit. non (Desf.) Ball, D. communis Rouy & E.G. Camus proles communis, Queen Anne's Lace

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.

Documented constituents refer to the fruit or seeds obtained from the dried fruit unless otherwise stated.

Flavonoids Flavones (e.g. apigenin, chrysin, luteolin), flavonols (e.g. kaempferol, quercetin) and various glycosides.(1)

Furanocoumarin 8-Methoxypsoralen and 5-methoxypsoralen (0.01–0.02 mg/g fresh weight) in fresh plant. Concentrations increased in the diseased plant.(2)

Volatile oils 0.66–1.65%.(3) Many components identified; relative composition varies between different cultivars.(3) Various components include a-pinene, b-pinene, geraniol, geranyl acetate, limonene, a-terpinen, p-terpinen, a-terpineol, terpinen-4-ol, p-

Figure 1 Selected constituents of wild carrot.

decanolactone (monoterpenes); b-bisabolene, b-elemene, caryophyllene, caryophyllene oxide, carotol, daucol (sesquiterpenes); asarone (phenylpropanoid derivative).(3)

Other constituents Choline,(4) daucine (alkaloid), a tertiary base (uncharacterised),(5) fatty acids (butyric, palmitic), coumarin, xylitol (polyol).

Food Use

Wild carrot should not be confused with the common cultivated carrot, D. carota L. subsp. sativus (Hoffm.) Arcang., which has

the familiar fleshy orange-red edible root. Wild carrot has an inedible tough whitish root.(G41) Wild carrot is listed by the

Council of Europe as a natural source of food flavouring (categories N1, N3). Category N1 indicates that for the roots there are no restrictions on use, whereas category N3 indicates that there is insufficient information available for an adequate assessment of potential toxicity.(G16)

Herbal Use

Wild carrot is stated to possess diuretic, antilithic, and carminative properties. Traditionally, it has been used for urinary

calculus, lithuria, cystitis, gout, and specifically for urinary gravel

or calculus.(G6, G7, G8, G64)

W

Dosage

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

Dried herb 2–4 g as an infusion three times daily.(G6, G7)

Liquid extract 2–4 mL (1 : 1 in 25% alcohol) three times

daily.(G6, G7)

594 Wild Carrot

Figure 2 Wild carrot (Daucus carota).

Pharmacological Actions

In vitro and animal studies

Significant antifertility activity (60%) in rats has been reported for wild carrot.(6) In contrast, insignificant antifertility activity was observed in pregnant rats fed oral doses of up to 4.5 g/kg body weight from day 1 to day 10 of pregnancy.(7) Aqueous, alcoholic and petrol extracts were reported to exhibit 20%, 40% and 10% activities respectively. Weak oestrogenic activity(6, 8, 9) and inhibition of implantation(6, 9) have been documented for seed extracts.(8) Oestrogenic activity, demonstrated by the inhibition of ovarian hypertrophy in hemicastrated rats, has been attributed to the known constituent coumarin (a weak phytooestrogen).(10)

Central effects similar to those of barbiturates have been

documented for the seed oil obtained from D. carota L. var. sativa DC.(11) The oil was reported to elicit CNS hypnotic effects in the

rat, hypotension in the dog(4) leading to respiratory depression at higher doses, anticonvulsant activity in the frog, in vitro smooth muscle relaxant activity reducing acetylcholine-induced contractions (ileum/uterus, rabbit/rat), antagonism of acetylcholine in isolated frog skeletal muscle, direct depressant effect on cardiac muscle in the dog.(4, 11) In vitro cardiotonic activity(4) and vasodilation of coronary vessels of the isolated cat heart have been reported.(12) Papaverine-like antispasmodic activity has been documented for a tertiary base isolated from wild carrot seeds.(5) Activity of approximately one-tenth that of papaverine was noted in a number of isolated preparations: ileum, uterus, blood vessels and trachea.(5) Cholinergic-type actions have also been reported

Wfor wild carrot with in vitro spasmodic actions noted in both smooth and skeletal muscle.(4) This cholinergic activity has been attributed to choline.(13) The identity of a second quaternary base isolated was not established.

Terpinen-4-ol is a documented component of the seed oil. This

constituent is considered to be the diuretic principle in juniper (see Juniper).

Increased resistance to carbon tetrachloride-induced hepatotoxicity has been reported in rats fed wild carrot.(14)

Limited antifungal activity has been documented, with activity

exhibited against only one (Botrytis cinerea) out of nine fungi tested.(15)

Agglutination of Streptococcus mutans cells has been described for wild carrot. The agglutinin, found to be heat and trypsin stable but sensitive to dextranose, was thought to be a dextran.(16)

Clinical studies

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

Side-effects, Toxicity

Clinical data

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

The oil is reported to be generally non-irritating and nonsensitising.(12) However, hypersensitivity reactions, occupational

dermatitis and positive patch tests have been reported for wild carrot.(2, G51) Wild carrot is reported to have a slight photo-

sensitising effect.(2) Furanocoumarins are known photosensitisers.

Preclinical data

The oil is reported to be of low toxicity. Acute LD50 values in mice (oral) and guinea-pigs (dermal) are reported to exceed 5 g/kg.(17)

Contra-indications, Warnings

Fruit extracts may cause sensitivity reactions similar to those seen with celery.(2)

Drug interactions None documented. However, the potential for preparations of wild carrot 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 wild carrot seed extracts have oestrogenic activity.

Pregnancy and lactation The safety of wild carrot has not been established. In view of this, the use of wild carrot during pregnancy and lactation should be avoided.

Preparations

Proprietary multi-ingredient preparations

Argentina: Hepatalgina; Hepatalgina; Metiogen; Palatrobil. Chile: Natur-Zin; Natursel-C. Italy: Evamilk. Malaysia: Eyebright Plus. UK: Sciargo; Watershed.

References

1El-Moghazi AM et al. Flavonoids of Daucus carota. Planta Med 1980; 40: 382–385.

2 Ceska O et al. Furocoumarins in the cultivated carrot, Daucus carota.

Phytochemistry 1986; 25: 81–83.

3Benecke R et al. Vergleichende Untersuchungen über den Gehalt an ätherischem Öl und dessen Zusammensetzung in den Früchten verschiedener Sorten von Daucus carota L. ssp. sativus (Hoffm.)

Arcang. Pharmazie 1987; 42: 256–259.

4Gambhir SS et al. Studies on Daucus carota, Linn. Part I. Pharmacological studies with the water-soluble fraction of the alcoholic extract of the seeds: a preliminary report. Indian J Med Res 1966; 54: 178–187.

5Gambhir SS et al. Antispasmodic activity of the tertiary base of

Daucus carota, Linn. seeds. Indian J Physiol Pharmacol 1979; 23: 225–

228.

6Prakash AO. Biological evaluation of some medicinal plant extracts for contraceptive efficacy. Contracept Deliv Syst 1984; 5: 9.

7Lal R et al. Antifertility effect of Daucus carota seeds in female albino rats. Fitoterapia 1986; 57: 243–246.

8Kant A et al. The estrogenic efficacy of carrot (Daucus carota) seeds. J Adv Zool 1986; 7: 36–41.

9Sharma MM et al. Estrogenic and pregnancy interceptory effects of carrot Daucus carota seeds. Indian J Exp Biol 1976; 14: 506–508.

10Kaliwal BB, Rao MA. Inhibition of ovarian compensatory hypertrophy by carrot seed (Daucus carota) extract or estradiol-17b in hemicastrated albino rats. Indian J Exp Biol 1981; 19: 1058–1060.

11Bhargava AK et al. Pharmacological investigation of the essential oil

of Daucus carota Linn. var. sativa DC. Indian J Pharm 1967; 29: 127– 129.

12Carrot seed oil. Food Cosmet Toxicol 1976; 14: 705–706.

13Gambhir SS et al. Studies on Daucus carota, Linn. Part II. Cholingergic activity of the quaternary base isolated from watersoluble fraction of alcoholic extracts of seeds. Indian J Med Res 1966; 54: 1053–1056.

14Handa SS. Natural products and plants as liver protecting drugs. Fitoterapia 1986; 57: 307–351.

15Guérin J-C, Réveillère H-P. Antifungal activity of plant extracts used in therapy. II Study of 40 plant extracts against 9 fungi species. Ann Pharm Fr 1985; 43: 77–81.

16Ramstorp M et al. Isolation and partial characterization of a substance from carrots, Daucus carota, with ability to agglutinate cells of Streptococcus mutans. Caries Res 1982; 16: 423–427.

17Opdyke DLJ. Carrot seed oil. Food Cosmet Toxicol 1974; 14: 705.