Chamomile, Roman

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Summary and Pharmaceutical Comment

The chemistry of Roman chamomile, particularly of the volatile oil, is well documented and is similar to that of German chamomile. Limited pharmacological data are available for Roman chamomile, although many actions have been reported for German chamomile. In view of the similar chemical compositions, many of the activities described for German chamomile are thought to be applicable to Roman chamomile and thus support the traditional herbal uses. However, rigorous clinical research assessing the efficacy and safety of preparations of Roman chamomile is required. Roman chamomile is stated to be of low toxicity, although allergic reactions (mainly contact dermatitis) have been reported.

Species (Family)

Chamaemelum nobile (L.) All. (Asteraceae/Compositae)

Synonym(s)

Anthemis nobilis L., Chamomile, ormenis nobilis (L.) J. Gay ex Coss. & Germ.

Part(s) Used

Flowerhead

Pharmacopoeial and Other Monographs

BHC 1992(G6)

BHP 1996(G9)

BP 2007(G84)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

USP29/NF24(G86)

Legal Category (Licensed Products)

GSL(G37)

Constituents

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

Coumarins Scopoletin-7-glucoside.

Flavonoids Apigenin, luteolin, quercetin and their glycosides (e.g. apiin, luteolin-7-glucoside and rutin).

Volatile oils 0.4–1.75%. Angelic and tiglic acid esters (85%);(1) others include 1,8-cineole, l-trans-pinocarveol, l-trans-pinocar- vone, chamazulene, farnesol, nerolidol; germacranolide-type sesquiterpene lactones (0.6%),(2) including nobilin, 3-epinobilin, 1,10-epoxynobilin, 3-dehydronobilin; various alcohols including amyl and isobutyl alcohols, anthemol.(1–4) Chamazulene is formed from a natural precursor during steam distillation of the oil, and varies in yield depending on the origin and the age of flowers.(1)

Other constituents Anthemic acid (bitter), phenolic and fatty acids, phytosterol, choline and inositol.

Food Use

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

used as an ingredient of herbal teas. Previously, Roman chamomile has been listed as GRAS (Generally Recognised As Safe).(G41)

Herbal Use

Roman chamomile is stated to possess carminative, anti-emetic, antispasmodic, and sedative properties. It has been used for dyspepsia, nausea and vomiting, anorexia, vomiting of pregnancy,

dysmenorrhoea, and specifically for flatulent dyspepsia associated with mental stress.(G2, G6, G7, G8, G64)

Dosage

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

Dried flowerheads 1–4 g as an infusion three times daily.(G7)

Liquid extract 1–4 mL (1 : 1 in 70% alcohol) three times daily.(G7)

Figure 1 Selected constituents of Roman chamomile.

Pharmacological Actions

German and Roman chamomile possess similar pharmacological activities (see Chamomile, German for a fuller description of documented pharmacological actions).

In vitro and animal studies

Few studies have been documented specifically for Roman chamomile. The azulene compounds are reported to possess anti-allergic and anti-inflammatory properties; their mechanism of action is thought to involve inhibition of histamine release (see Chamomile, German). The volatile oil has been documented as having anti-inflammatory activity (carrageenan rat paw oedema test), and antidiuretic and sedative effects following intraperito-

neal administration of doses up to 350 mg/kg body weight to rats.(5)

The azulenes have been reported to stimulate liver regeneration following oral, but not subcutaneous, administration.

The sesquiterpenoids nobilin, 1,10-epoxynobilin and 3-dehy- dronobilin have demonstrated in vitro antitumour activity against human cells.(1) The concentration of hydroxyisonobilin required for cytotoxic activity is reported to be low enough to warrant further investigations (ED50 0.56 mg/mL versus HeLa; ED50 1.23 mg/mL versus KB; arbitrary acceptable test level 4 mg/mL).

Clinical studies

Clinical research assessing the effects of Roman chamomile is limited, and rigorous randomised controlled clinical trials are required.

Side-effects, Toxicity

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

Instances of allergic and anaphylactic reactions to chamomile have been documented (see Chamomile, German) The allergenic principles in chamomile are thought to be the sesquiterpene

emetic(G44) and this has been attributed to the anthemic acid content.(6)

The acute toxicity of Roman chamomile in animals is reported to be relatively low.(1) Acute LD50 values in rabbits (dermal) and rats (by mouth) have been stated to exceed 5 g/kg.(2)

Contra-indications, Warnings

In view of the documented allergic reactions and cross-sensitivities (see Chamomile, German), Roman chamomile should be avoided by individuals with a known hypersensitivity to any members of the Asteraceae/Compositae family. In addition, Roman chamomile may precipitate an allergic reaction or exacerbate existing symptoms in susceptible individuals (e.g. asthmatics).

The use of chamomile preparations in teething babies is not recommended.

Drug interactions None documented. However the potential for preparations of Roman chamomile to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered (particularly where oral preparations of Roman chamomile are used). Coumarin compounds detected so far in Roman chamomile do not possess the minimum structural requirements (a C-4 hydroxyl substituent and a C-3 non-polar carbon substituent) for anticoagulant activity.

Pregnancy and lactation Roman chamomile is reputed to be an abortifacient and to affect the menstrual cycle.(G30) In view of this and the potential for allergic reactions, the excessive use of Roman chamomile during pregnancy and lactation should be avoided.

Preparations

Proprietary multi-ingredient preparations

UK: Summertime Tea Blend.

158 Chamomile, Roman

References

1Mann C, Staba EJ. The chemistry, pharmacology, and commercial formulations of chamomile. In: Craker LE, Simon JE, eds. Herbs, Spices, and Medicinal Plants: Recent Advances in Botany,

Horticulture, and Pharmacology, vol 1. Arizona: Oryx Press, 1986:

C2 Opdyke DLJ. Chamomile oil roman. Food Cosmet Toxicol 1974: 12: 853.235–280.

3 Casterline CL. Allergy to chamomile tea. JAMA 1980; 4: 330–331. 4 Hausen BM et al. The sensitizing capacity of Compositae plants.

Planta Med 1984; 50: 229–234.

5 Melegari M et al. Chemical characteristics and pharmacological properties of the essential oils of Anthemis nobilis. Fitoterapia 1988; 59: 449–455.

6Achterrath-Tuckermann U et al. Pharmacologisch Untersuchungen von Kamillen-Inhaltestoffen. Planta Med 1980; 39: 38–50.

Chaparral

Summary and Pharmaceutical Comment

The chemistry of chaparral is well studied and extensive literature has been published on the principal lignan component nordihydroguaiaretic acid (NDGA). However, little documented evidence is available to justify the herbal uses of chaparral. In view of the concerns over the hepatic toxicity, the use of chaparral as a herbal remedy cannot be recommended.

Species (Family)

Larrea tridentata Cov. var. glutinosa Jepson (Zygophyllaceae)

Synonym(s)

Creosote Bush. L. tridentata (south-western USA and northern Mexico) is now regarded as a separate species to Larrea divaricata Gav. (north-western Argentina).(1)

Part(s) Used

Herb

Pharmacopoeial and Other Monographs

Martindale 35th edition(G85)

Legal Category (Licensed Products)

Chaparral is not included in the GSL.(G37)

Constituents

The following is compiled from several sources, including General Reference G22.

Amino acids Arginine, aspartine, cystine, glutamic acid, glycine, isoleucine, leucine, phenylalanine, tryptophan, tyrosine and valine.

Flavonoids More than 20 different compounds reported, including isorhamnetin, kaempferol and quercetin and their glycosidic and ether derivatives; gossypetin, herbacetin, and their acetate derivatives;(1–7) two C-glucosyl flavones.

Lignans Major constituent nordihydroguaiaretic acid (NDGA) (up to 1.84%), norisoguaiacin, dihydroguaiaretic acid, partially

demethylated dihydroguaiaretic acid, 30-demethoxyisoguaia-

cin.(8–10)

Figure 1 Selected constituents of chaparral.

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Resins 20%. Phenolic constituents on external leaf surfaces of L. divaricata and L. tridentata are reported to be identical, containing a number of flavone and flavonol glycosides, and two lignans (including NDGA).(5)

Volatile oils Many identified terpene components include

calamene, eudesmol, limonene, a- and b-pinene, and 2-rossa- lene.(11)

Other constituents Two pentacyclic triterpenes,(12) saponins.

Other plant parts A cytotoxic naphthoquinone derivative, larreantin, has been isolated from the roots.(13)

Food Use

Chaparral is not used in foods, although a related species, Larrea mexicana Moric., also termed creosote bush, is listed by the Council of Europe as a natural source of food flavouring (category N2). This category indicates that creosote bush can be added to foodstuffs in small quantities, with a possible limitation of an active principle (as yet unspecified) in the final product.(G16) In the USA, NDGA is no longer permitted to be used as an antioxidant in foods following the results of toxicity studies in animals (see Side-effects, Toxicity).

Herbal Use

Chaparral has been used for the treatment of arthritis, cancer,

venereal disease, tuberculosis, bowel cramps, rheumatism and colds.(G60)

Figure 2 Chaparral (Larrea tridentata).

160 Chaparral

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Figure 3 Chaparral – dried drug substance (herb).

Dosage

None documented.

Pharmacological Actions

In vitro and animal studies

Amoebicidal action against Entamoeba histolytica has been reported for a chaparral extract (0.01%).(14) This action may be attributable to the lignan constituents, which are documented as both amoebicidal and fungicidal.(9) NDGA has been reported to have antimicrobial activity against a number of organisms including Penicillium spp., Salmonella spp., Streptococcus spp., Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and various other pathogens and moulds.(8, 15)

NDGA is an antioxidant, and has been documented to cause inhibition of hepatic microsomal enzyme function.(15–17)

Clinical studies

Medical interest in chaparral increased following claims that ingestion of an aqueous infusion of the herb was associated with regression of a malignant melanoma in the cheek of an 85-year-old man.(18) However, an isolated care report is not adequate scientific evidence, results of a subsequent study that investigated the antitumour action of chaparral, as a tea, were inconclusive.(G60)

Side-effects, Toxicity

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

Acute hepatitis has been associated with chaparral inges- tion.(19–21) Contact dermatitis to chaparral has been reported.(22, 23) Chaparral-induced toxic hepatitis has been reported for two patients in different parts of the USA. The adverse effects were attributed to ingestion of a herbal nutritional supplement derived from the leaves of chaparral. Five cases of serious poisoning in the USA and another three in Canada have been linked to chaparral-containing products.(20, 24) Some patients have developed irreversible reno-hepatic failure. Initially, NDGA was thought to have low toxicity: doses of up to 400 mg/kg body weight by intramuscular injection had been administered to humans for 5–6 months, with little or no toxicity reported.(15)

Documented oral LD50 values for NDGA include 4 g/kg (mouse), 5.5 g/kg (rat) and 830 mg/kg (guinea-pig).(15) Results of chronic

feeding studies (two years, 0.25–1.0% of diet) in rats and mice

reported no abnormalities in histological tests of the liver, spleen and kidney. Inflammatory caecal lesions and slight cystic enlargement of lymph nodes near the caecum were observed in rats at the 0.5% feeding level. At this point NDGA was considered to be safe for food use. However, two later studies in rats (using NDGA at up to 3% of the diet) reported the development of cortical and medullary cysts in the kidney.(15) On the basis of these findings, NDGA was removed from GRAS (Generally Recognised As Safe) status in the USA and is no longer permitted to be used as an antioxidant in foods.(15)

Contra-indications, Warnings

In view of the reports of acute hepatitis associated with chaparral ingestion, and the uncertainty regarding NDGA toxicity, consumption should be avoided.

Drug interactions None documented. However the potential for preparations of chaparral to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered. Chaparral has amino acid constituents and, therefore, may not be suitable for use by patients receiving treatments with monoamine oxidase inhibitors.

Pregnancy and lactation In vitro utero activity has been documented for chaparral.(G30) In view of the concerns regarding toxicity, chaparral should not be ingested during pregnancy or lactation.

Preparations

Proprietary multi-ingredient preparations

Australia: Proyeast.

References

1Bernhard HO, Thiele K. Additional flavonoids from the leaves of

Larrea tridentata. Planta Med 1981; 41: 100–103.

2Sakakibara M et al. 6,8-Di-C-glucosylflavones from Larrea tridentata (Zygophyllaceae). Phytochemistry 1977; 16: 1113–1114.

3Sakakibara M et al. A new 8-hydroxyflavonol from Larrea tridentata. Phytochemistry 1975; 14: 2097–2098.

4Sakakibara M et al. New 8-hydroxyflavonols from Larrea tridenta. Phytochemistry 1975; 14: 849–851.

5Sakakibara M et al. Flavonoid methyl ethers on the external leaf surface of Larrea tridentata and L. divaricata. Phytochemistry 1976; 15: 727–731.

6Chirikdjian JJ. Isolation of kumatakenin and 40,5-dihydroxy-3,30,7- trimethoxyflavone from Larrea tridentata. Pharmazie 1974; 29: 292–

293.

7 Chirikdjian JJ. Flavonoids of Larrea tridentata. Z Naturforsch 1973; 28: 32–35.

8 Gisvold O, Thaker E. Lignans from Larrea divaricata. J Pharm Sci 1974; 63: 1905–1907.

9Fronczek FR et al. The molecular structure of 30- demethoxynorisoguaiacin triacetate from creosote bush (Larrea

tridentata). J Nat Prod 1987; 50: 497–499.

10Page JO. Determination of nordihydroguaiaretic acid in creosote bush. Anal Chem 1955; 27: 1266–1268.

11Bohnstedt CF, Mabry TJ. The volatile constituents of the genus Larrea (Zygophyllaceae). Rev Latinoam Quim 1979; 10: 128–131.

12Xue H-Z et al. 3-b-(3,4-Dihydroxycinnamoyl)-erythrodiol and 3b-(4- hydroxycinnamoyl)-erythrodiol from Larrea tridentata. Phytochemistry 1988; 27: 233–235.

13Luo Z et al. Larreatin, a novel, cytotoxic naphthoquinone from Larrea tridentata. J Org Chem 1988; 53: 2183–2185.

14Segura JJ et al. In-vitro amebicidal activity of Larrea tridentata. Bol Estud Med Biol 1979; 30: 267–268.

15Oliveto EP. Nordihydroguaiaretic acid. A naturally occurring antioxidant. Chem Ind 1972: 677–679.

16Burk D, Woods M. Hydrogen peroxide, catalase, glutathione peroxidasequinones, nordihydroguaiaretic acid, and phosphopyridine in relation to X-ray action on cancer cells. Radiation Res Suppl 1963; 3: 212–246.

17Pardini RS et al. Inhibition of mitochondrial electron transport by nor-dihydroguaiaretic acid (NDGA). Biochem Pharmacol 1970; 19: 2695–2699.

18Smart CR et al. An interesting observation on nordihydroguaiaretic acid (NSC-4291; NDGA) and a patient with malignant melanoma—a preliminary report. Cancer Chemother Rep Part 1 1969; 53: 147.

Chaparral 161

19Katz M, Saibil F. Herbal hepatitis: subacute hepatic necrosis secondary to chaparral leaf. J Clin Gastroenterol 1990; 12: 203–206.

20Clark F, Reed R. Chaparral-induced toxic hepatitis – California and Texas, 1992. Morb Mortal Wkly Rep 1992; 41: 812–814.

21Gordon DW et al. Chaparral ingestion – the broadening spectrum of

23Shasky DR. Contact dermatitis from Larrea tridentata (creosote bush). J Am Acad Dermatol 1986; 15: 302.

24Anon. Toxic tea. Pharm J 1993; 250: 366.