(2004; 358 pages)
Radix Angelicae Sinensis
Radix Angelicae Sinensis consists of the dried roots of Angelica sinensis (Oliv.) Diels (Apiaceae) (1).
Although Angelica sinensis has also been referred to as Angelica polymorpha Maxim. var. sinensis (the latter being a synonym for A. polymorpha Maxim. (2)), their synonymy has not yet been firmly established (J.C. Regalado, personal communication, 1999). Apiaceae are also known as Umbelliferae.
Selected vernacular names
Can qui, Chinese Angelica, dangdanggui, dang gui, dong quai, duong qui handanggui, hashyshat almalak, kara toki, langdu danggui, min-gui, tang-kuei, tangkuei tân qui (1, 3-6).
Indigenous to China (3, 4).
A fragrant, perennial herb, 0.5-1.0 m high. Stem glabrous and purplish, with light, linear striations. Inferior leaves tripinnate; superior leaves often pinnate; segments oval, dentate-incised, teeth obtuse. Petiole 3-11 cm long, sheathed; bracts rudimentary, not prominent. Umbels 10-14, radiate on top of the plant, rays irregular, interior margin uneven; bracteoles, narrow-linear 2-4; pedicels slender; carpophore bipartite; each umbel multiflorous (12-36 flowers); umbel stem 0.3-1.5 cm long. Flowers white, 5 petals, glabrous, incurvate at the tips. Carpels dorsally compressed, square-elliptical, the base cordiform, the tip rounded or lightly notched; dorsal veins 5, closely placed, projecting; central vein barely winged, marginal veins with very large wings; ducts oleaginous, 1 in each sinus, 2 in the commissure (4).
Plant material of interest: dried roots
Somewhat cylindrical, 3-5 or more branches at the lower part, 15-25 cm long. Externally yellowish-brown to brown, longitudinally wrinkled and transversely lenticellate. Root stocks 1.5-4 cm in diameter, annulated, apex obtuse, showing purple or yellowish-green remains of stems and leaf sheaths; main roots lumpy on the surface, branching roots 0.3-1.0 cm in diameter, upper portion thick and lower portion thin, mostly twisted, with a few rootlet scars. Texture flexible, fracture yellowish-white or yellowish-brown, thick epidermis, showing some clefts and numerous brown spotted secretory cavities; wood paler in colour than the bark, cambium ring yellowish-brown (1).
Odour: strongly aromatic; taste: sweet, pungent, slightly bitter (1).
Cork cells in several layers. Cortex narrow, with a few scattered oil cavities. Phloem cleft, broad (25-160µm in diameter), relatively large on outer side, gradually becoming smaller, surrounded by 6-9 secretory cells, oil cavities and oil tubes. Cambium in a ring. Xylem rays, 3-5 cells wide; vessels scattered singly or in groups of 2-3, arranged radially; parenchymatous cells contain starch grains (1).
Powdered plant material
Yellowish-brown; parenchymatous cells in phloem are fusiform, with slightly thickened walls, very oblique criss-cross striations, thin transverse septa sometimes visible; scalariform and reticulate vessels frequent, up to 80µm in diameter; fragments of oil cavities sometimes visible (1).
General identity tests
Macroscopic and microscopic examinations (1).
Tests for specific microorganisms and microbial contamination limits are as described in the WHO guidelines on quality control methods for medicinal plants (7).
Foreign organic matter
Free of foreign matter (1).
Not more than 7.0% (1).
Not more than 2.0% (1).
Not less than 45% using 70% ethanol (1).
The recommended maximum limit of aldrin and dieldrin is not more than 0.05 mg/kg (8). For other pesticides, see the European pharmacopoeia (8), and the WHO guidelines on quality control methods for medicinal plants (7) and pesticide residues (9).
For maximum limits and analysis of heavy metals, consult the WHO guidelines on quality control methods for medicinal plants (7).
Where applicable, consult the WHO guidelines on quality control methods for medicinal plants (7) for the analysis of radioactive isotopes.
Other purity tests
Chemical, water-soluble extractive and loss on drying tests to be established in accordance with national requirements.
Methods for both qualitative and quantitative determination of the alkyl phthalide components by high-performance liquid chromatography have been developed (10, 11). National requirements for quantitative criteria should be established with respect to the concentration ranges reported for the essential oil (0.4-0.7%) (4) and ligustilide (0.5-5.0%) (10).
Major chemical constituents
The characteristic components are the simple alkyl phthalides (ligustilide, (Z)- ligustilide, (Z)-6,7-epoxyligustilide, angelicide, (Z)-butylidenephthalide, butylphthalide, 2,4-dihydrophthalic anhydride), which are the major components of the essential oil fraction of the roots. Other characteristic components of the oil have been identified as terpenes (β-cadinene, carvacrol and cis-β-ocimene). The non-volatile constituents reported are phenylpropanoids ((E)-ferulic acid, coniferyl ferulate); benzenoids (valerophenone-o-carboxylic acid and vanillic acid); and coumarins (angelol G, angelicone and umbelliferone) (3, 4, 10, 11). It has been shown by high-performance liquid chromatography that the major chemical constituent of the roots is ligustilide, which can account for over 5% (10). Polysaccharide fractions of low relative molecular mass have also been reported (12, 13). The structures of the characteristic constituents are presented below.
Uses supported by clinical data
None. Although Radix Angelicae Sinensis has been alleged to be useful for the treatment of menopausal symptoms, a randomized, placebo-controlled clinical trial concluded that 4.5 g of the root daily for 24 weeks did not alleviate menopausal symptoms, such as hot flushes (14).
Uses described in pharmacopoeias and in traditional systems of medicine
Treatment of menstrual disorders such as irregular menstruation, amenorrhoea and dysmenorrhoea (1, 3, 15-19). As an analgesic for symptomatic treatment of rheumatic arthralgia, abdominal pain and in the management of postoperative pain (1, 20). Treatment of constipation (1), anaemia (1, 20), chronic hepatitis and cirrhosis of the liver (20).
Uses described in folk medicine, not supported by experimental or clinical data
Treatment of dehydration, lumbago, abnormal menstruation, menopausal symptoms (including hot flushes), hypertonia and nervous disorders (18, 21).
Smooth muscle contraction
Hot aqueous extracts of Radix Angelicae Sinensis stimulated smooth muscle contractions of the bladder, intestine and uterus when administered intravenously to dogs (10 g/kg body weight) (22). Intravenous administration of an aqueous or 95% ethanol extract of the roots to cats, rats and rabbits increased the strength of the contractions and tone of uterine smooth muscles (4). In vitro assays demonstrated that a decoction of the roots stimulated the H1 receptor of mouse uterus (23). The active constituent responsible for this activity is an aqueous- and alcohol-soluble, non-volatile component, the structure of which is unknown (4). Conversely, ligustilide, a constituent of the essential oil of the roots, inhibited contractions of isolated uteri from various animal models (20, 24). Intraperitoneal administration of ligustilide (0.14ml/kg body weight) to guinea-pigs inhibited asthmatic reactions induced by acetylcholine and histamine (25). Ligustilide (32.5-130.0 µl/ml) inhibited smooth muscle contractions induced by barium sulfate, acetylcholine and histamine in isolated guinea-pig trachea (25).
Intraperitoneal administration of a decoction of the roots (11ml/kg body weight) ameliorated galactosamine-induced hepatotoxicity in rats (26). Ferulic acid, a constituent of the roots, protected rat liver mitochondria against damage induced by oxygen free radicals (27). Intragastric pretreatment of mice with sodium ferulate (100 mg/kg body weight) daily for 10 days alleviated liver toxicity induced by paracetamol (28) and prednisolone (29), and bromobenzeneinduced liver injury (30).
Cardiac haemodynamic studies demonstrated that intravenous administration of an aqueous root extract (2 g/kg body weight) to anaesthetized dogs increased coronary blood flow from 88 ml before administration to 128 ml (per 100g cardiac muscle/minute post-injection). Coronary vascular resistance and myocardial oxygen consumption also decreased, while the heart rate decreased or remained unchanged (31). An extract of the roots increased coronary blood flow in isolated guinea-pig hearts (32).
In animal models, both aqueous and ethanol extracts of the roots had an effect on arrhythmias induced by epinephrine, barium chloride and digitalis (32, 33). Intravenous administration of an ethanol extract of the roots (4g/kg body weight) antagonized chloroform- and epinephrine-induced arrhythmias in cats (34). Ethanol extracts of the roots and ferulic acid restored normal sinus rhythm after ouabain-induced arrhythmia in isolated ventricular muscle from cats (20). Aqueous extracts of the roots reduced the action potential amplitude and maximal upstroke velocity of the Q phase, and prolonged the effective refractory period and the duration of the action potential in guinea-pig myocardium (35). Intravenous administration of an aqueous extract of the roots (50mg/kg body weight) to rabbits with ligation of the left anterior descending coronary artery provided protection against ischaemia- and reperfusion-induced myocardial dysfunction and injury (36). An aqueous extract of the roots bound to nitrendipine and diltiazem receptors, thereby demonstrating calcium channel blocking activity (37). A ligustilide dimer, isolated from the roots, inhibited [3H]nitrendipine binding to dihydropyridine-sensitive calcium channels (inhibitory concentration of 50% [IC50] 0.4 µmol/l) (38). Since calcium channel blockers are known to have pronounced effects on the cardiovascular system, this activity may explain some of the reported effects of root extracts on the cardiovascular system.
In vitro and in vivo studies have shown that extracts of the roots inhibit platelet aggregation and have antithrombotic activity (20). Aqueous extracts of the roots (200 mg/ml) or ferulic acid (0.4 mg/ml) inhibited platelet aggregation induced by ADP or collagen in vitro (39). A hot aqueous extract of the roots (500mg/ml) or ferulic acid (1 mg/ml) inhibited thrombin-induced platelet aggregation and release of [3H]5-hydroxytryptamine from labelled platelets in vitro (39). An aqueous extract of the roots inhibited both ADP- and collagen-induced platelet aggregation when administered intravenously to rats (200 mg/ml) (20, 39). The mechanism of action appears to be via inhibition of cyclooxygenase and throm-boxane A2 synthase by ferulic acid, leading to decreased production of thromboxane A2 (40). The antithrombotic activity of the drug is associated with inhibition of platelet aggregation, reduction in the concentration of plasma fibrinogen, changes in cell surface charge and a decrease in blood viscosity (20).
Intraperitoneal administration of polysaccharides isolated from the roots increased haematopoiesis in mouse bone marrow, as determined by an increase in colony-forming units in the marrow cells (12, 41). The polysaccharides promoted the proliferation and differentiation of haematopoietic progenitor cells in healthy and anaemic mice (13). Results of this study indicated that the polysaccharides may enhance haematopoiesis by stimulating macrophages, fibroblasts and lymphocytes in haematopoietic and muscle tissue to secrete haematopoietic growth factor (13).
Although there are a number of case reports concerning the clinical use of Radix Angelicae Sinensis in the treatment of amenorrhoea and dysmenorrhoea, these studies were published between 1899 and 1910 (15-18). Randomized, controlled clinical trials are needed to confirm these observations. In these early case studies, female patients were treated with 5 ml of a fluidextract of the roots three times daily before meals for 1 week before menstruation. The treatment relieved premenstrual pain and induced menstrual flow in most cases. No abortifacient activity was observed in two pregnant women treated with the same fluidextract (15). In other studies, the fluidextract was used for the treatment of dysmenorrhoea in nulliparous women, and of severe bleeding in multiparous women. Administration of 5 ml of the fluidextract three times daily for 1 week before menstruation was effective in decreasing menstrual pain and chronic endometritis (16). Successful treatment of amenorrhoea and dysmenorrhoea in female patients was further reported after administration of the same fluidextract (5 ml, three times daily) (17, 18). In another report, 112 women with dysmenorrhoea were treated for 3-7 days with ligustilide dimer isolated from the roots. The efficacy rate was 77%. Minor side-effects were nausea and dizziness, which disappeared after the treatment stopped (42).
Smooth muscle contraction
Decoctions of the roots reportedly stimulated uterine smooth muscle in female patients, but the doses used and the conditions being treated were not stated (19). A decoction of the roots lowered whole blood viscosity after administration to six patients (11).
Radix Angelicae Sinensis should not be administered to children or patients with diarrhoea, haemorrhagic diseases or hypermenorrhoea, and should not be used during pregnancy or lactation (4).
No information available.
Decreased prothrombin times were reported in rabbits that received both a single subcutaneous dose of warfarin (2 mg/kg body weight) and a repeated oral dose of Radix Angelicae Sinensis (2g/kg body weight twice daily for 3 days) (43). Therefore, patients receiving anticoagulant therapy should be advised against taking Radix Angelicae Sinensis without medical supervision.
Pregnancy: teratogenic effects
Pregnancy: non-teratogenic effects
No information available on general precautions or precautions concerning drug and laboratory test interactions; or carcinogenesis, mutagenesis and impairment of fertility.
Oral administration of Radix Angelicae Sinensis is generally regarded as having few side-effects; however, headaches may occur in sensitive individuals (14, 19). No adverse reactions were reported in 40 people who received an aqueous root extract by intravenous administration (240 ml/person) for 30 days (19).
Powdered crude drug and fluidextracts (4). Store in an airtight container in a cool, dry place protected from moisture (1).
(Unless otherwise indicated)
Daily dosage: 4.5-9 g crude drug (1).
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