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WHO Monographs on Selected Medicinal Plants - Volume 2
(2004; 358 pages) View the PDF document
Table of Contents
View the documentIntroduction
View the documentGeneral technical notices
View the documentRadix Althaeae
View the documentHerba Andrographidis
View the documentRadix Angelicae Sinensis
View the documentFlos Calendulae
View the documentFlos Caryophylli
View the documentRhizoma Cimicifugae Racemosae
View the documentFolium cum Flore Crataegi
View the documentRadix Eleutherococci
View the documentAetheroleum Eucalypti
View the documentFolium Eucalypti
View the documentCortex Frangulae
View the documentFolium et Cortex Hamamelidis
View the documentSemen Hippocastani
View the documentHerba Hyperici
View the documentAetheroleum Melaleucae Alternifoliae
View the documentFolium Melissae
View the documentAetheroleum Menthae Piperitae
View the documentFolium Menthae Piperitae
View the documentFolium Ocimi Sancti
View the documentOleum Oenotherae Biennis
View the documentRhizoma Piperis Methystici
View the documentCortex Pruni Africanae
View the documentCortex Rhamni Purshianae
View the documentFlos Sambuci
View the documentRadix Senegae
View the documentFructus Serenoae Repentis
View the documentFructus Silybi Mariae
View the documentHerba Tanaceti Parthenii
View the documentRadix Urticae
View the documentFolium Uvae Ursi
View the documentAnnex: Participants in the Second WHO Consultation on Selected Medicinal Plants
 

Radix Angelicae Sinensis

Definition

Radix Angelicae Sinensis consists of the dried roots of Angelica sinensis (Oliv.) Diels (Apiaceae) (1).

Synonyms

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).

Geographical distribution

Indigenous to China (3, 4).

Description

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

General appearance

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).

Organoleptic properties

Odour: strongly aromatic; taste: sweet, pungent, slightly bitter (1).

Microscopic characteristics

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).

Purity tests

Microbiological

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).

Total ash

Not more than 7.0% (1).

Acid-insoluble ash

Not more than 2.0% (1).

Alcohol-soluble extractive

Not less than 45% using 70% ethanol (1).

Pesticide residues

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).

Heavy metals

For maximum limits and analysis of heavy metals, consult the WHO guidelines on quality control methods for medicinal plants (7).

Radioactive residues

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.

Chemical assays

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.


(Z)-ligustilide


angelicide


(Z)-butylidenephthalide ((Z)-ligusticum lactone)


β-cadinene


carvacrol


cis-β-ocimene


(E)-ferulic acid R = H coniferyl ferulate R = Con


valerophenone-o-carboxylic acid (ligusticumic acid)


vanillic acid

 

R5

R6

R7

R8

         

umbelliferone

H

H

H

H

         

angelicone

OCH3

H

CH3

Sen

         

angelol G

H

Ang

CH3

H



Ang = angeloyl


Con = (E)-coniferyl


Sen = senecioyl

Medicinal uses

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).

Pharmacology

Experimental pharmacology

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).

Antihepatotoxic activity

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).

Cardiovascular activity

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.

Antithrombotic activity

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).

Clinical pharmacology

Menstrual disorders

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).

Contraindications

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).

Warnings

No information available.

Precautions

Drug interactions

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

See Contraindications.

Pregnancy: non-teratogenic effects

See Contraindications.

Nursing mothers

See Contraindications.

Paediatric use

See Contraindications.

Other precautions

No information available on general precautions or precautions concerning drug and laboratory test interactions; or carcinogenesis, mutagenesis and impairment of fertility.

Adverse reactions

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).

Dosage forms

Powdered crude drug and fluidextracts (4). Store in an airtight container in a cool, dry place protected from moisture (1).

Posology

(Unless otherwise indicated)

Daily dosage: 4.5-9 g crude drug (1).

References

1. Pharmacopoeia of the People’s Republic of China. Vol. I (English ed.). Beijing, Chemical Industry Press, 1997.

2. Hiroe M. Umbelliferae of Asia. Kyoto, Eikodo, 1958.

3. Hsu HY. Oriental materia medica, a concise guide. Long Beach, CA, Oriental Healing Arts Institute, 1986.

4. Zhu DPQ. Dong quai. American Journal of Chinese Medicine, 1987, 15:117-125.

5. Farnsworth NR, ed. NAPRALERT database. Chicago, University of Illinois at Chicago, IL, January 1, 1998 production (an online database available directly through the University of Illinois at Chicago or through the Scientific and Technical Network [STN] of Chemical Abstracts Services).

6. Medicinal plants in Viet Nam. Manila, World Health Organization, 1990 (WHO Regional Publications, Western Pacific Series, No. 3).

7. Quality control methods for medicinal plant materials. Geneva, World Health Organization, 1998.

8. European pharmacopoeia, 3rd ed. Strasbourg, Council of Europe, 1996.

9. Guidelines for predicting dietary intake of pesticide residues, 2nd rev. ed. Geneva, World Health Organization, 1997 (document WHO/FSF/FOS/97.7).

10. Lin LZ et al. Liquid chromatographic-electrospray mass spectrometric study of the phthalides of Angelica sinensis and chemical changes of Z-ligustilide. Journal of Chromatography A, 1998, 810:71-79.

11. Terasawa K et al. Chemical and clinical evaluation of crude drugs derived from Angelica acutiloba and A. sinensis. Fitoterapia, 1985, 56:201-208.

12. Ma LF et al. The effect of Angelica sinensis polysaccharides on mouse bone marrow hematopoiesis. Zhonghua Xinxueguanbing Zazhi, 1988, 9:148-149.

13. Wang Y, Zhu B. The effect of Angelica polysaccharide on proliferation and differentiation of hematopoietic progenitor cells. Chung Hua I Hsueh Tsa Chih, 1996, 76:363-366.

14. Hirata JD et al. Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertility and Sterility, 1997, 68:981-986.

15. Mueller A. Versuche über die Wirkungsweise des Extrakts des chinesischen Emmenagogon Tang-kui (Man-mu) oder Eumenol-Merek. Münchener Medizinische Wochenschrift, 1899, 46:796-798.

16. Langes H. Beobachtungen bei der Verwendung einiger neuer Medikamente. Eumenol, Dionin und Stypticin. Therapeutische Monatshefte, 1901, 7:363.

17. Palm R. Erfahrungen mit Eumenol. Münchener Medizinische Wochenschrift, 1910, 1: 23-25.

18. Buck P. Un nouveau remède spécifique contre la dysmenorrhée: l’eumenol. Belgique médicale, 1899, 2:363-365.

19. Chang HM, But PPH, eds. Pharmacology and applications of Chinese materia medica. Vol. 1. Philadelphia, PA, World Scientific Publishing, 1986.

20. Mei QB, Tao JY, Cui B. Advances in the pharmacological studies of Radix Angelica sinensis (Oliv.) Diels (Chinese danggui). Chinese Medical Journal, 1991, 104:776-781.

21. Duke JA, Ayensu ES. Medicinal plants of China. Vol. 1. Algonac, MI, Reference Publications, 1985.

22. Schmidt CF et al. Experiments with Chinese drugs. 1. Tang-kuei. Chinese Medical Journal, 1924, 38:362.

23. Shi M, Chang L, He G. Stimulating action of Carthamus tinctorius L., Angelica sinensis (Oliv.) Diels and Leonurus sibiricus L. on the uterus. Chung Kuo Chung Yao Tsa Chih, 1995, 20:173-175.

24. Pi XP. Effects of Angelica sinensis on uterus. National Medical Journal of China, 1955, 40:967.

25. Tao JY et al. Studies on the antiasthmatic action of ligustilide of dang-gui, Angelica sinensis (Oliv.) Diels. Yao Hsueh Hsueh Pao, 1984, 198:561-565.

26. Xiong X et al. The protective effect of Radix Angelicae Sinensis against acute liver damage by D-galactosamine in rats: a histochemical study. Wu-han I Hsueh Yuan Hsueh Pao, 1982, 11:68-72.

27. Lin YH et al. Protective effect of sodium ferulate on damage of the rat liver mitochondria induced by oxygen free radicals. Yao Hsueh Hsueh Pao, 1994, 29:171-175.

28. Wang H, Peng RX. Sodium ferulate alleviated paracetamol-induced liver toxicity in mice. Yao Hsueh Hsueh Pao, 1994, 15:81-83.

29. Wu DF et al. Sodium ferulate alleviates prednisolone-induced liver toxicity in mice. Acta Pharmaceutica Sinica, 1988, 30:801-805.

30. Wu DF, Peng RX. The effect of sodium ferulate on bromobenzene-induced liver injury in mice. Zhongguo Yaoxue Zazhi, 1995, 30:597-599.

31. Chou YP. The effect of Angelica sinensis on hemodynamics and myocardiac oxygen consumption in dogs. Acta Pharmaceutica Sinica, 1979, 14:156-160.

32. Pen RX. Pharmacological effects of danggui (Angelica sinensis) on cardiovascular system. Chinese Traditional Herb Drugs, 1981, 12:321.

33. Cha L. Effects of Angelica sinensis on experimental arrhythmias. Chinese Pharmaceutical Bulletin, 1981, 16:259.

34. Cha L, Chien CC, Lu FH. Antiarrhythmic effect of Angelica sinensis root, tetrandrine and Sophora flavescens root. Chinese Pharmaceutical Bulletin, 1981, 16:53-54.

35. Wei ZM et al. A study on the electrophysiology in antiarrhythmia effect of Angelica sinensis. Journal of Beijing College of Traditional Chinese Medicine, 1985, 8:40.

36. Chen SG et al. Protective effects of Angelica sinensis on myocardial ischemia/ reperfusion injury in rabbits. Chung-kuo Chung His I Chieh Ho Tsa Chih, 1995, 15:486-488.

37. Hon PM. A ligustilide dimer from Angelica sinensis. Phytochemistry, 1990, 29:1189-1191.

38. Han GQ. The screening of Chinese traditional drugs by biological assay and the isolation of some active components. International Journal of Chinese Medicine, 1991, 16:1-17.

39. Yin ZZ. The effect of danggui (Angelica sinensis) and its ingredient ferulic acid on rat platelet aggregation and release of 5-HT. Acta Pharmaceutica Sinica, 1980, 15:321.

40. Xu LN. Effect of sodium ferulate on arachidonic acid metabolism. Acta Pharmaceutica Sinica, 1990, 25:412.

41. Chen YC, Gao YQ. Research on the mechanism of blood-tonifying effect of danggui buxue decoction. Chung Kuo Chung Yao Tsa Chih, 1994, 19:43-45, 63.

42. Compendium of materia medica. Shanghai, State Administration of Traditional Chinese Medicine, Shanghai Science and Technical Press, 1996:1341-1355.

43. Lo A et al. Danggui (Angelica sinensis) affects the pharmacodynamics but not the pharmacokinetics of warfarin in rabbits. European Journal of Drug Metabolism and Pharmacokinetics, 1995, 20:55-60.

 

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