Aetheroleum Anisi, Herbal Medicine

Defi nition
Aetheroleum Anisi consists of the essential oil obtained by steam distillation
from the dry ripe fruits of Pimpinella anisum L. (Apiaceae) (1–5).1

Anisum offi cinarum Moench, A. vulgare Gaertn., Apium anisum (L.)
Crantz, Carum anisum (L.) Baill., Pimpinella anisum cultum Alef., P. aromatica
Bieb., Selinum anisum (L.) E.H.L. Krause, Sison anisum Spreng.,
Tragium anisum Link (1, 6–8). Apiaceae are also known as Umbelliferae.

Selected vernacular names
Anacio, Anes, Aneis, anice, anice verde, Anis, anisbibernelle, anis verde,
anis vert, anise, anisoon, anisum, anizs, anizsolaj, annsella, badian, badian
rumi, boucage, boucage anis, Gruner Anis, habbat hlawa, jintan manis,
jinten manis, petit anis, pimpinelle, razianag, razianaj, roomy, saunf, sweet
cumin, yansoon (1, 6–10).

Geographical distribution
Indigenous to the eastern Mediterranean region, western Asia and Europe.
Cultivated in southern Europe and northern Africa, and in Argentina,
Bulgaria, Chile, China, India, Islamic Republic of Iran, Japan, Mexico,
Romania, Russian Federation and Turkey (8).


An aromatic annual herb, up to 60 cm high with an erect, cylindrical,
striated, smooth stem. Leaves alternate below, opposite above, the lower
being long-petioled, ovate–orbicular, dentate, the upper with short dilated
petioles, pinnatifi d or ternately pinnate with long, entire or cut cuneate
segments. Infl orescence long-stalked, compound umbel with 8–14 rays;
fl owers small, white, each on a long hairy pedicel. Fruit comprises a
1 The European pharmacopoeia (5) permits the inclusion of the essential oil of Illicium verum Hook.
mouse-shaped cremocarp with a small stylopod and two minutely pubescent
mericarps that do not readily separate from the carpophore (6, 11).

Plant material of interest: essential oil

General appearance

A clear, colourless or pale yellow liquid, solidifying on cooling, practically
insoluble in water, miscible with alcohol, ether, light petroleum or
methylene chloride (1, 5).

Organoleptic properties
Odour: characteristic, aromatic; taste: sweet, strongly aromatic (1).

Microscopic characteristics

Not applicable.

Powdered plant material

Not applicable.

General identity tests
Thin-layer chromatography for the presence of anethole, anisaldehyde
and linalool. A gas chromatography method is also available (5).

Purity tests
Tests for specifi c microorganisms and microbial contamination limits are
as described in the WHO guidelines on quality control methods for medicinal
plants (12).

Soluble in three parts ethanol (90%) at 20 oC (4). Relative density 0.978–
0.994 (5). Refractive index 1.552–1.561 (5). Freezing-point 15–19 oC (5).
Acid value not more than 1.0 (5).

Pesticide residues
The recommended maximum limit of aldrin and dieldrin is not more than
0.05 mg/kg (5). For other pesticides, see the European pharmacopoeia (5),
and the WHO guidelines on quality control methods for medicinal plants
(12) and pesticide residues (13).

Heavy metals
For maximum limits and analysis of heavy metals, consult the WHO
guidelines on quality control methods for medicinal plants (12).
Aetheroleum Anisi

Other purity tests
Tests for foreign organic matter, total ash, acid-insoluble ash, water-soluble
extractive, alcohol-soluble extractive and loss on drying not applicable.

Chemical assays
Contains 0.1–1.5% linalool, 0.5–6.0% methylchavicol, 0.1–1.5% α-terpineol,
< 0.5% cis-anethole, 84–93% trans-anethole, 0.1–3.5% p-anisaldehyde

Major chemical constituents
The major constituents are trans-anethole (84–93%), cis-anethole (< 0.5%),
methylchavicol (estragole, isoanethole; 0.5–6.0%), linalool (0.1–1.5%) and
p-anisaldehyde (0.1–3.5%) (5). The structures of trans-anethole, methylchavicol,
β-linalool and p-anisaldehyde are presented below.

Medicinal uses
Uses supported by clinical data


Uses described in pharmacopoeias and well established documents

Treatment of dyspepsia and mild infl ammation of the respiratory tract
(14, 15).

Uses described in traditional medicine
As an aphrodisiac, carminative, emmenagogue, galactagogue and insecticide.
Treatment of chronic bronchitis (8, 10).

Experimental pharmacology
Anticonvulsant activity
Intraperitoneal administration of 1.0 ml/kg body weight (bw) of the oil to
mice suppressed tonic convulsions induced by pentylenetetrazole or
maximal electroshock (22). Intraperitoneal administration of 2.5 g/kg bw
of linalool to rodents provided protection against convulsions induced by
pentylene tetrazole, picrotoxin and electroshock (23, 24). Intraperitoneal
administration of 2.5 g/kg bw of linalool to mice interfered with glutamate
function and delayed convulsions induced by N-methyl-d-aspartate
(25). Linalool acts as a competitive antagonist of [3H]-glutamate
binding and as a non-competitive antagonist of [3H]-dizocilpine binding
in mouse cortical membranes. The effects of linalool were investigated on
[3H]-glutamate uptake and release in mouse cortical synaptosomes. Linalool,
1.0 mmol/l, reduced potassium-stimulated glutamate release (26).
These data suggest that linalool interferes with elements of the excitatory
glutamatergic transmission system.

Anti-infl ammatory activity
Anethole is a potent inhibitor of tumour necrosis factor (TNF)-induced
nuclear factor (NF)-κβ activation, inhibitor-κβα phosphorylation and
degradation, and NF-κβ reporter gene expression in vitro, demonstrating
that anethole suppresses infl ammation by inhibiting TNF-induced cellular
responses (27).
Aetheroleum Anisi

Antispasmodic activity
The oil inhibited the phasic contractions of ileal myenteric plexus-longitudinal
muscle preparations isolated from guinea-pigs in vitro, median effective
dose 60 mg/l (28). The oil, 1:20 000, decreased the rate and extent
of contractions in intestinal smooth muscle isolated from rats, cats or rabbits
in vitro, and antagonized the stimulant activity of acetylcholine, barium
chloride, pilocarpine and physostigmine (29). Anethole, 0.05–1.00 mg/
ml, blocked twitching induced by acetylcholine and caffeine in toad rectus
abdominis and sartorius muscles, but had no effect on skeletal muscle
twitching induced by nerve stimulation in isolated rat diaphragm (30).

Bronchodilatory activity
The oil, 1.0 mmol/l, had relaxant effects in precontracted, isolated guineapig
tracheal chains indicating a bronchodilatory effect. It also induced a
parallel rightwards shift in the methacholine-response curve (methacholine
is a muscarinic receptor antagonist), indicating that the bronchodilatory
activity may be due to an inhibitory effect of the oil on the
muscarinic receptors (31).

Estrogenic activity
Subcutaneous administration of 0.1 ml of the oil to ovariectomized rats
had an estrogenic effect equivalent to that of 0.1 μg of estradiol (32). Intraperitoneal
administration of 0.1 ml of the oil had a uterine relaxation effect
in female rats (32). Anethole is thought to be the estrogenic component
of the oil; polymers of this compound, such as dianethole and
photoanethole, have also been suggested (33).

Expectorant activity
Intragastric administration of 10.0–50.0 mg/kg bw of the oil to guineapigs
increased bronchial secretions, demonstrating an expectorant effect
(34). Intragastric administration of two drops of the oil as an emulsion
with gummi arabicum to cats induced hypersecretion of the respiratory
tract (35). However, other researchers have demonstrated that administration
of the oil to cats by steam inhalation had no effect on respiratory
tract fl uid except when given in toxic doses, which increased the output
(36). Administration of the oil by inhalation to anaesthetized rabbits did
not appreciably affect respiratory tract fl uids until doses of 720.0 mg/kg
bw and over were used in a vaporizer (36, 37). At this dose, 20% of the
animals died and there was local irritation of the lining of the respiratory
tract, which appeared as congestion at 6 hours and progressed to leukocytic
infi ltration and destruction of the ciliated mucosa at 24 hours (36).
Inhalation of 1 ml/kg bw of anisaldehyde in anaesthetized rabbits signifi -
cantly increased (P < 0.05) the volume of respiratory fl uid collected for
4–6 hours after treatment and decreased the specifi c gravity of the fl uid in
treated animals compared with untreated controls (38).

Liver effects
Subcutaneous administration of 100.0 mg/kg bw of the oil per day for
7 days stimulated liver regeneration in partially hepatectomized rats (39).

The oral median lethal dose (LD50) of anisaldehyde in rats was 1.51 g/kg
bw, with death occurring within 4–18 hours following depression of the
central nervous system (40). The oral LD50 in guinea-pigs was 1.26 g/kg
bw, death occurring after 1–3 days (40).
The safety and metabolism of trans-anethole were evaluated in rats as
a model for assessing the potential for hepatotoxicity in humans exposed
to the compound as a fl avouring agent. In chronic dietary studies in rats,
hepatotoxicity was observed when the estimated daily hepatic production
of anethole epoxide exceeded 30 mg/kg bw. Chronic hepatotoxicity and a
low incidence of liver tumours were observed at a dietary intake of transanethole
of 550.0 mg/kg bw per day (41). The effects of trans-anethole on
drug metabolizing enzymes were assessed in rats; intragastric administration
of 125.0 mg/kg or 250.0 mg/kg bw per day for 10 days had no effect
on total cyctochrome P450 content in liver microsomes (42). In a chronic
feeding study, trans-anethole was administered to rats in the diet at concentrations
of 0, 0.25%, 0.5% and 1.0% for 117–121 weeks, giving an average
dose of 105–550.0 mg/kg bw per day. No abnormalities related to
treatment were observed with the exception of a very low incidence of
hepatocarcinomas in female animals treated with the 1.0% dose (43).
The acute oral LD50 of anethole in rats was 2090.0 mg/kg bw; repeated
doses of 695.0 mg/kg bw caused mild liver lesions consisting of slight discoloration,
mottling and blunting of the lobe edges (33).

Clinical pharmacology
The absorption of anethole from the gastrointestinal tract was assessed in
healthy volunteers. The drug was rapidly absorbed from the gastrointestinal
tract and rapidly eliminated in the urine (54–69%) and through
the lungs (13–17%). The principal metabolite was 4-methoxyhippuric
acid (approximately 56%); other metabolites were 4-methoxybenzoic
acid and three other unidentifi ed compounds (44, 45). Increases in drug
dose did not alter the pattern of metabolite distribution in humans, contrary
to fi ndings in animal models (46).
Aetheroleum Anisi

Adverse reactions
Contact dermatitis was reported in a cake factory worker after external
exposure to a 5% concentration of Aetheroleum Anisi (47). Occasional
allergic reactions to the oil affecting the skin, respiratory tract and gastrointestinal
tract are reported (15). Inhalation of powdered Fructus Anisi
induced an allergic effect in one subject with asthma. Skin-prick tests
showed a positive reaction to the fruits and the patient had high specifi c
anti-aniseed immunoglobulin E antibodies in his blood (48). Anethole
toxicity in infants has been reported, and presents clinically with symptoms
of hypertonia, continued crying, atypical ocular movements, twitching,
cyanosis, vomiting and lack of appetite (7, 49). Ingestion of 1.0–5.0 ml
of the oil can result in nausea, vomiting, seizures and pulmonary oedema
(50). In cases of overdose (> 50 mg/kg), the ingestion of milk and alcohol
is contraindicated owing to increased resorption.

Aetheroleum Anisi is contraindicated in cases of known allergy to aniseed
and anethole (48). Owing to the traditional use of the oil as an emmenagogue
and to induce labour, its experimental estrogenic and potential mutagenic effects,
and reports of anethole toxicity in infants (7, 49), use of the oil in pregnancy
and nursing, and in children under the age of 12 years is contraindicated.

Applications of Aetheroleum Anisi should be limited to inhalation therapy

Carcinogenesis, mutagenesis, impairment of fertility
Inconsistent results have been reported concerning the mutagenicity of
trans-anethole in the Salmonella/microsome assay. One group showed
that anethole was mutagenic (52), another that it was very weakly mutagenic
in S. typhimurium strains TA1535, TA100 and TA98 (53). In a further
study, trans-anethole (concentrations not specifi ed) did not increase
the mutant frequency in the Salmonella/microsome assay, but did increase
mutant frequency in the L5178Y mouse-lymphoma TK+/- assay in a
dose-dependent manner, with metabolic activation (49). Trans-anethole
did not induce chromosome aberrations in vitro in the Chinese hamster
ovary cell assay (49). Trans-anethole was weakly hepatocarcinogenic in
female rats when administered at a dose of 1% in the diet for 121 weeks;
however, this effect is not mediated by a genotoxic event (54). Trans-anethole
was investigated for its antifertility activity in rats, after intragastric
administration of doses of 50.0 mg/kg bw, 70.0 mg/kg bw and 80.0 mg/kg
bw (55). Anti-implantation activity of 100% was observed in animals
treated with the highest dose. The compound has been reported to show
estrogenic, antiprogestational, androgenic and antiandrogenic activities

Pregnancy: non-teratogenic effects
See Contraindications.

Nursing mothers
See Contraindications.

Paediatric use
See Contraindications.

Other precautions
No information available on general precautions or on precautions concerning
drug interactions; drug and laboratory test interactions; and teratogenic
effects in pregnancy.

Dosage forms
Essential oil. Preparations containing 5–10% essential oil for inhalation
are also available. Store in a well-fi lled, tightly sealed container, protected
from light and heat (5).

(Unless otherwise indicated)
Average daily dose for internal use: essential oil 0.3 g; equivalent for other



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