Angelica sinensis (Oliv.) Diels.

Dong quai

Other names

dong quai (English), dang gui (Mandarin), toki (Japanese), tanggwi (Korean)

Botanical synonym is Angelica polymorpha.

Description

Family

Apiaceae (formerly known as Umbelliferae)

Botanical description

Angelica sinensis is a perennial fragrant plant. Stem grows to 1 metre, is hollow, fluted, glabrous, smooth, purplish, with light linear striations. Superior leaves are simply pinnate, inferior leaves tripinnate. Segments are oval, dentate-incised, with obtuse teeth. Petiole is sheathed, to 11 cm; bracts are redimentary, not prominent.

Umbel is multiflorous with 12 to 36 greenish-white flowers. Stem of umbel flowers grows to 1.5 cm. Flowers have 5 petals, no hair, incurvate at tips. Carpels are dorsally compressed, square-elliptical, the base cordiform, the tip rounded or lightly notched, 5 dorsal veins are closely placed, projecting, the central vein barely winged, marginal veins with large wings. Ducts are oleaginous, solitary in each sinus, 2 in commisure.

The axial root is conical, with several fibrous roots, 15 cm long, the root base 1.5 - 4.0 cm in diameter, brown in colour. Cork longitudinally and transversely lenticellate. The root body longitudinally wrinkled. The root base rounded flat, with lanceolate stem leaf remnant lying flat at its top. Prepared by crosscutting, the section showing a cortex with brown spotted oil cavities and an even xylem, cambium ring appearing between them. Soft in texture; delicately fragrant in smell; sweet and acrid in taste.

Angelica sinensis is native to China. It prefers cold, damp mountain slopes at high altitudes.

Other species

Other Angelica species used medicinally include: A. dahuricae Benth. and Hook. [China, Japan], A. gigas Nakai [Korea], and A. pubescens Maxim.

Part used

The root is the medicinal part used.

Traditional use

Eastern traditional medicine

The experience of traditional Chinese medicine affords a valuable approach in the search for new antineoplastic drugs, as illustrated by indirubin from Dang Gui Lu Hui Wan (see below). It is, however, important that the terminology used in Traditional Chinese Medicine (TCM) is not taken literally. The TCM term 'spleen' does not mean spleen in the modern sense, instead it refers to the entire gastrointestinal system. Similarly, the TCM term for 'kidney' does not mean kidney in the modern sense, and can mean the entire endocrine system. It is important to analyse these terms within the framework of TCM for the integration of traditional medicine into modern medicine.1

Indirubin is an antileukemic compound isolated from the Chinese herb Indigo naturalis (Qing-dai), Baphicacanthus cusia, Indigofera tinctoria, Polygonum tingctorium or Isatis tingctoris. Qing-dai has been used in the traditional Chinese prescription Dang Gui Lu Hui Wan in the treatment of chronic myelocytic leukemia. Inhibition of cyclin-dependent kinase 1 (CDK) activity in human tumour cells is a major mechanism by which indirubin derivatives exert their potent antitumour efficacy.2

Activity According to TCM

  • TCM Taste and Qualities: Sweet, acrid, bitter and warm
  • Tonifies blood and regulates menstruation.
  • Used for deficient blood patterns with symptoms of pale face, tinnitus, blurred vision, palpitations. Also for deficient blood with menstrual irregularities, amenorrhoea, dysmenorrhoea.
  • Invigorates and harmonises blood and is used to stop pain from congealed blood.
  • Moistens intestines and moves the stool. Used for dry intestines from deficient blood.

Active constituents

  • Essential oil containing ligustilide, angelicide, n- butylidene phthalide, butylphthalide, 2,4-dihydrophthalic anhydride. The essential oil consists mainly of ligustilide and n-butylidene phthalide. 3 N-butylidene phthalide is responsible for the characteristic fragrance of the oil. The high quality boxed root heads are extremely high in active constituents, containing as much as 5% ligustilide which is more than 10 times the level in normal commercial roots.
  • Coumarins including angelol and angelicone3
  • Phenylpropanoids including ferulic acid4
  • Angelica polysaccharides5
  • Phospholipids6

Complete list of constituents and amount (when available) listed in Duke's phytochemical and ethnobotanical databases7

ALPHA-PINENE Root:
ALUMINUM Root 422 ppm;
ARACHIDONIC-ACID Root:
ASCORBIC-ACID Root 304 ppm;
ASH Root 56 000 ppm;
BERGAPTEN Root:
BETA-CAROTENE Root 12.1 ppm;
BETA-SITOSTEROL Root:
BETA-SITOSTEROL-GLUCOSIDE Root:
BIOTIN Root:
CADINENE Root:
CALCIUM Root 1680 - 2820 ppm
CARBOHYDRATES Root 800 000 ppm;
CARVACROL Root:
CHOLINE Root 2470 ppm;
CHROMIUM Root 9 ppm;
COBALT Root 151 ppm;
COPPER Root 5 ppm;
EO Root 2000 - 7000 ppm
FALCARINDIOL Root:
FALCARINOL Root:
FALCARINONE Root:
FAT Root 18 000 ppm;
FERULIC-ACID Root:
FIBER Root 172 000 ppm;
FOLACIN Root:
FOLINIC-ACID Root:
FRUCTOSE Root:
GLUCOSE Root:
IRON Root 750 - 880 ppm
ISOSAFROLE Root:
KILOCALORIES Root 2820 /kg;
LIGUSTILIDE Root:
LINOLEIC-ACID Root:
MAGNESIUM Root 1650 - 2650 ppm
MANGANESE Root 26 - 71 ppm
MYRISTIC-ACID Root:
N-BUTYLIDENPHTHALIDE Root:
N-BUTYLPHTHALIDE Root:
N-DODECANOL Root:
N-VALEROPHENONE-O-CARBONIC-ACID Root:
N-VALEROPHENONE-O-CARBOXYLIC-ACID Root:
NICOTINAMIDE Root:
NICOTINIC-ACID Root:
OLEIC-ACID Root:
P-CYMENE Root:
PALMITIC-ACID Root:
PANTOTHENIC-ACID Root:
PHOSPHORUS Root 3340 ppm;
PHTHALIDES Root:
POTASSIUM Root 10 700 - 16 800 ppm
PROTEIN Root 130 000 ppm;
RIBOFLAVIN Root 3.4 ppm;
SAFROLE Root:
SCOPOLETIN Root:
SEDANOIC-ACID Root:
SELENIUM Root:
SESQUITERPENE Root:
SILICON Root 34 ppm;
SODIUM Root 539 ppm;
STEARIC-ACID Root:
SUCROSE Root:
THIAMIN Root:
TIN Root 4 ppm;
UMBELLIFERONE Root:
VANILIC-ACID Root:
VIT-B12 Root:
VIT-E Root 77 ppm;
WATER Root 780 000 ppm;
ZINC Root 17 ppm;

ppm = parts per million
tr = trace

Pharmacological studies

Cardiovascular effects

Cardiotonic activity

  • Angelica sinensis has been shown to have a quinidine-like action on the heart. It can prolong the refractory period and correct experimental atrial fibrillation induced by atropine, pituitrin, strophanthin, acetylcholine or electrical stimulation.8

Antiplatelet Activity

  • An early study has demonstrated antiplatelet activity.9 Ferulic acid, as well as the aqueous extract of Angelica sinensis, was shown to have an antiplatelet effect.8

Protection Against Reperfusion Injury

  • The injection of aqueous extract of Angelica sinensis exerted significant protective effects on myocardial dysfunction and myocardial injury in rabbits induced by ischemia/reperfusion.10
  • Pre-treatment with a traditional formulation, 'Dang gui decoction for Enriching the Blood' which contains Angelica sinensis and Astragalus membranaceus as the main ingredients, was shown to give protection against ischaemia-reperfusion injury in isolated rat myocardiums. The effect was enhanced by the addition of another herb, Polygonum multiflorum.11

Prevention of atherogenesis

  • Human umbilical vein endothelial cells were used to investigate the role of angelica in human vascular damage. Angelica sinensis protected against oxidation of low-density lipoproteins and inhibits changes to the function and structure of vascular endothelial cells thereby reducing the development of atherogenesis.12
  • Animal study found that Angelica sinensis can reduce atherogenesis through decreasing the serum triglyceride concentration, increasing whole blood viscosity and by regulating haematocrit and fibrinogen levels.13

Antioxidant activity

  • Angelica sinensis root extract demonstrated antioxidant activity and inhibition of lipid peroxidation of supernatant hepati homogenate in mice. It was further demonstrated that different extract manufacturing processes affected the level of activity.14

Effects on the blood

  • Angelica polysaccharides were found to enhance haematopoiesis by directly or indirectly stimulating macrophages, fibroblasts and lymphocytes to secrete haematopoietic growth factor in healthy and anaemic mice.15
  • In TCM, Angelica sinensis is indicated for 'stagnated blood'. A model of 'blood stagnation' was established in rats using adrenaline and a cold environment. The condition produced an increase in the viscosity of the blood and in the liability to coagulate. Astragalus membranaceus and Angelica sinensis both decreased whole blood specific viscosity while at the same time increase the plasma specific viscosity. The combination of the herbs had a more favourable effect.16
  • Angelica sinensis has been shown to increase red blood cell counts.17
  • Dang-Gui-Shao-Yao-San (DGSYS) which contains Angelica sinensis, is known to elevate haematopoietic functions during single X-irradiation. DGSYS given at doses of 10 and 20 mg/20 g body weight, once a day, for 7 consecutive days before irradiation protected mice from the sublethal effects of radiation in a dose-dependent manner. Prior administration of 20 mg/20 g DGSYS increased the number of femoral spleen colony-forming units (CFU-S) that survived irradiation, and significantly ameliorated leukopenia, thrombocytopaenia and the degression of haematocrits after irradiation. These results suggest that DGSYS may be effective in the prevention of haematopoietic injury caused by sublethal dose irradiation.18

Uterine effects

  • Contrary to popular belief, Angelica sinensis has been found to be without any direct oestrogenic activity.8
  • Angelica sinensis has been shown to increase sexual activity in female animals and a reduction in the signs of vitamin E deficiency has been noted in male mice.3
  • Butylidenephthalide has been shown to inhibit rat uterine contractions.19
  • Angelica sinensis decoction has been found to have a stimulating action on the uterus of mouse in vitro.20
  • Ferulic acid showed an inhibitory effect on uterine movement when given perorally and intravenously, respectively.21

Immunity

  • Ferulic acid has been shown to increase phagocytosis.22
  • Angelica sinensis can somewhat counter the immunosuppressive effects of hydrocortisone, although Astragalus membranaceous was found to be more effective.23
  • A low molecular weight polysaccharide consisting of protein (4.73%) and carbohydrate (85.85%) of which 5.2% is uronic acid, was shown to exert a strong anti-tumor activity on Ehrlich ascites tumor bearing mice. It also exhibited immunostimulating activities, both in vitro and in vivo.5
  • A TCM preparation (Dang gui Buxue decoction) significantly (P < 0.001) promoted the production of interleukin-2 (IL-2) in the spleen of blood-deficient mice. Individual analysis of the herbal formula showed that IL-2 production can be promoted in splenic lymphocytes of blood-deficient mice given Angelica sinensis or Astragalus membranaceus (P < 0.001).24

Anti-inflammatory action

  • Early experimental models have indicated that Angelica sinensis may have anti-asthmatic activity25 and be of benefit in nepheritis.26
  • Angelica sinensis injection increased the production of interleukin-2 in mouse spleen mononuclear cells. The stimulatory effect was totally abrogated by the addition of prostaglandin E2.27
  • Ferulic acid (FA) significantly inhibited the edema induced by carrageenan, the increase of the dye leakage induced by acetic acid and the granuloma formation induced by cotton pellet. And also inhibited the number of writhes induced by acetic acid. From these results, it is suggested that ferulic acid has both anti-inflammatory effect and analgesic effects. The author furthermore suggested that ferulic acid exert an anti-inflammatory effect both at the early and the late stages of processes in the inflammatory pathology.28
  • Angelica sinensis markedly inhibited the formation of thromboxane A2 and mildly affected the formation of prostaglandin I2.29
  • Angelica polysaccharides were shown to have anti-inflammatory activity, perhaps through the inhibitory action on neutrophil infiltration in the gastrointestinal mucosa. Angelica polysaccharides could potentially be useful to prevent any neutrophil-dependent mucosal injury in the gastrointestinal tract.30
  • The crude extract of Angelica sinensis was shown to have a direct mucosal healing effect on gastric epithelial cells, promoting healing of gastric ulcer.31
  • A crude extract from Angelica sinensis (ASCE), which mainly consisted of polysaccharides, prevented ethanol- or indomethacin-induced gastric mucosal damage and promoted ulcer healing. It was found that ASCE significantly promoted the migration of epithelial cells over an artificial wound on the surface of an RGM-1 monolayer. The extract also stimulated DNA synthesis in a dose-dependent manner and concomitantly increased EGF RNA expression. Co-incubation of ASCE with anti-EGF antibody reduced the speed of migration and the DNA synthesis, which however were still higher than the control without ASCE. These results strongly suggest that ASCE has a direct wound healing effect on gastric mucosa, and this is acting partially through an EGF-mediated pathway.32

Antitumour activity

  • In vitro study found that ligustilide demonstrated an anti-proliferative effect on smooth muscle cells.33

Hepatoprotective activity

  • Pre-treatment with sodium ferulate inhibited the activity of serum alanine aminotransferase, prevented the depletion of liver glycogen and glutathione, increased the liver homogenate and microsomal glutathione S-transferase activities, and reduced the malondialdehyde content, the membrane fluidity of liver microsome and the mitochondria in paracetamol-induced liver toxicity in mice. These results demonstrated the hepato-protective action of sodium ferulate in mice.34

Cognitive Function

  • A methanolic extract and its hexane fractions were shown to improve drug-induced amnesia in rats and it was shown that this effect was related to the memory processes. The hexane fraction was more effective indicating that highly non-polar constituents may be responsible for this effect.35

Clinical studies

Cardiovascular disorders

  • Uncontrolled clinical studies have shown Angelica sinensis to be beneficial in the treatment of Buerger's disease and constrictive aortitis.8
  • 40 patients with pulmonary hypertension in remission stage were equally divided into four groups, 10 cases in each. Group 1 was treated with an Angelica sinensis injection, Group 2 with nifedipine, Group 3 with both Angelica sinensis and nifedipine and Group 4 acted as the control group. The study was designed to investigate the changes of hemodynamics, pulmonary function and blood gas before and after the treatments by impedance rheopneumogram, lung function examination and blood gas analysis. The mean pulmonary arterial pressure was decreased and cardiac output, PaO2 were increased significantly (P < 0.05 or P < 0.01) in group 3. The effects of group 3 appeared to be better than in other groups. The side effect of PaO2 lowering in group 2 was overcome in adding Angelica sinensis.39

Endocrine disorders

  • Long-term treatment (9 months) of infertility due to tubal occlusion resulted in successful pregnancies in over 50% of cases.36
  • Ligustilide at 450 mg per day was shown to be twice as effective as a decoction of Angelica sinensis root in a study of 112 patients suffering dysmenorrhoea.37
  • A decoction of Angelica sinensis, Corydalis ambigua, Paeonia lactiflora and Ligusticum walichii showed a 93% improvement rate for the treatment of dysmenorrhoea. The decoction was given daily, starting 5 days before and until cessation of menstruation.38

Hepatic disorders

  • Angelica sinensis reduced thymol turbidity in an uncontrolled study of 88 cases of chronic hepatitis or liver cirrhosis.8

Actions

  • regulates uterine function, uterine tonic, mild emmenagogue, improves fertility
  • blood tonic
  • anti-anaemic
  • smooth muscle relaxant
  • cardiac tonic
  • immunostimulatory
  • anti inflammatory
  • liver protection
  • mildly sedative
  • anti-platelet
  • mild laxative
  • antiarrhythmic

Indications

Gynaecology

Angelica sinensis is considered to be a 'tonic' and 'amphoteric' to the uterus. It may relax uterine spasms during menstruation but may during labour, however, increase uterine tone and help establish regular and orderly contractions. It may also improve blood flow through the uterus. Angelica is thus indicated for dysmenorrhoea, amenorrhoea, irregular menstruation, menorrhagia, metrorrhagia, PMS, infertility and menopause when combined with other appropriate herbs such as Rehmannia glutinosa and Paeonia lactiflora.

Angelica sinensis is often combined with Bupleurum chinensis and Paeonia lactiflora for premenstrual irritability and debility, with Cinnamomum spp. for menstrual pain that is worse by cold, and with Corydalis ambigua and Paeonia lactiflora for dysmenorrhoea.

Menopause

Used alone, Angelica sinensis does not produce estrogen-like responses as measured by endometrial thickness or vaginal maturation and was no more helpful than placebo in relieving menopausal symptoms such as menopausal flushing.40 Angelica sinensis is however, often combined with Rehmannia glutinosa or Astragalus membranaceus in the treatment of hot flushes and debility associated with menopause.

Fertility

Use associated with improved fertility. 343 cases of infertility of more than 3 years associated with organic disease (74%) or functional disorders (26%), were treated with herbal medicines which included Angelica sinensis. 139 conceived. reference: Ruth??

Cardiovascular system

Due to its antioxidant, anti-arrhythmic, antiplatelet, cardiotonic and ability to relax arterial smooth muscle spasms, Angelica sinensis, combined with Salvia miltiorrhiza, is used in the treatment of palpitations, hypertension, cardiac arrhythmia, peripheral vascular disorders such as Buerger's disease, angina, cerebral ischaemia and stroke. Angelica sinensis is also used for blood disorder, both in terms of TCM blood deficiency and stagnation syndromes, and damage due to radiation.

Gastrointestinal tract

Angelica sinensis is spasmolytic to the smooth muscle of the gastrointestinal tract which improves constipation and spastic conditions, especially in the elderly. It is also used in combination with other herbs for chronic liver disorders. Preparations containing high levels of Angelica polysaccharides may be beneficial in gastric and intestinal ulcerative disorders.

Contraindications

  • First trimester of pregnancy
  • Menorrhagia associated with infection; retained membranes, placenta or conceptus after TOP or delivery.

Drug interaction

  • Angelica sinensis affects the pharmacodynamics but not the pharmacokinetics of warfarin in rabbits. The root extract was found to not increase prothrombin time by itself, but may lower prothrombin time when combined with warfarin.41
  • A 46-year old African-American woman with atrial fibrillation stabilised on warfarin experienced a greater than 2-fold elevation in prothrombin time and international normalized ratio after taking dong quai concurrently for 4 weeks. No identifiable cause was ascertained for the increase except dong quai. The patient's coagulation values returned to acceptable levels 1 month after discontinuing the herb.42

Toxicology

At concentrations greater than 2.5 grams/ml, Angelica sinensis extract exerted a general cytotoxicity to melanocytes in culture. Cytotoxicity was reduced by prior treatment of the extract with polyvinylpolypyrrolidone, which was shown by thin layer chromatography to reduce the coumarin content.43

The oral LD50 of a concentrated extract in rats was measured at 100g/kg body weight. According to information supplied by the author, this concentrated extract was 8-16:1.44

Side effects

Can occasionally cause mild gastrointestinal upsets which are often alleviated with ginger, cinnamon or bitters, as indicated.

Dosage

The daily dose is 4.5 to 9.0 grams of the root, taken as a tea in divided doses.

Liquid extract (1:2): 2-10 ml, usually around 4 ml daily.

Reference list

  1. Han J. Traditional Chinese medicine and the search for new antineoplastic drugs. J Ethnopharmacol 1988;24:1-17.
  2. Marko D, Schatzle S, Friedel A, et al. Inhibition of cyclin-dependent kinase 1 (CDK1) by indirubin derivatives in human tumour cells. Br J Cancer 2001;84:283-9.
  3. Zhu DP. Dong Quai. Am J Chin Med 1987;15:117-25.
  4. Ji SG, Chai YF, Wu YT, et al. Determination of ferulic acid in Angelica sinensis and Chuanxiong by capillary zone electrophoresis. Biomed Chromatogr 1999;13:333-4.
  5. Choy YM, Leung KN, Cho CS, et al. Immunopharmacological studies of low molecular weight polysaccharide from Angelica sinensis. Am J Chin Med 1994; 22:137-45.
  6. Guo R, Lu J, Xu Y. [Phospholipid components of danggui]. Zhongguo Zhong Yao Za Zhi 1991;16:741-2.
  7. Duke J. Phytochemical Database. USDA - ARS - NGRL, Beltsville Agricultural Research Center, Beltsville, Maryland. 2001.
  8. Chang H M, But PP. Pharmacology and Applications of Chinese Materia Medica. Singapore: World Scientific Press Co, 1987.
  9. Yin ZZ, Zhang LY, Xu LN. [The effect of Dang-Gui (Angelica sinensis) and its ingredient ferulic acid on rat platelet aggregation and release of 5-HT (author's transl)]. Yao Xue Xue Bao 1980;15:321-6.
  10. Chen SG, Li CC, Zhuang XX. [Protective effects of Angelica sinensis injection on myocardial ischemia/reperfusion injury in rabbits]. Zhongguo Zhong Xi Yi Jie He Za Zhi 1995;15:486-8.
  11. Yim TK, Wu WK, Pak WF, et al. Myocardial protection against ischaemia-reperfusion injury by a Polygonum multiflorum extract supplemented 'Dang-Gui decoction for enriching blood', a compound formulation, ex vivo. Phytother Res 2000;14:195-9.
  12. Xiaohong Y, Jing-Ping OY, Shuzheng T. Angelica protects the human vascular endothelial cell from the effects of oxidized low-density lipoprotein in vitro. Clin Hemorheol Microcirc 2000;22:317-23.
  13. Zhui Y, Jing-Ping OY, Yongming L, et al. Experimental study of the antiatherogenesis effect of Chinese medicine angelica and its mechanisms. Clin Hemorheol Microcirc 2000;22:305-10.
  14. Wu H, Kong L, Wu M, et al. [Effects of different processed products of radix Angelica sinensis on clearing out oxygen free radicals and anti-lipid peroxidation]. [Article in Chinese]. Zhongguo Zhong Yao Za Zhi 1996;21:599-601.
  15. Wang Y,.Zhu B. [The effect of angelica polysaccharide on proliferation and differentiation of haematopoietic progenitor cell]. Zhonghua Yi Xue Za Zhi 1996;76:363-6.
  16. Xue JX, Yan YQ, Jiang Y. [Effects of the combination of Astragalus membranaceus (Fisch.) Bge. (AM), Angelica sinensis (Oliv.) Diels (TAS), Cyperus rotundus L. (CR), Ligusticum chuangxiong Hort (LC) and Peaonia veitchii lynch (PV) on the hemorheological changes in "blood stagnating" rats]. Zhongguo Zhong Yao Za Zhi 1994;19:108-10.
  17. Chang H M. Advances in Chinese Medicinal Materials Research. Singapore: World Scientific, 1995.
  18. Hsu HY,.Lin CC. A preliminary study on the radioprotection of mouse haematopoiesis by dang-gui-shao-yao-san. J Ethnopharmacol 1996;55:43-8.
  19. Ko W. A newly isolated antispasmodic--butylidenephthalide. Jap J Pharmacol 1980;30:85-91.
  20. Shi M, Chang L, He G. [Stimulating action of Carthamus tinctorius L., Angelica sinensis (Oliv.) Diels and Leonurus sibiricus L. on the uterus]. Zhongguo Zhong Yao Za Zhi 1995;20:173-5.
  21. Ozaki Y,.Ma JP. Inhibitory effects of tetramethylpyrazine and ferulic acid on spontaneous movement of rat uterus in situ. Chem Pharm Bull (Tokyo) 1990; 38:1620-3.
  22. Xu LN, Ouyang R, Yin ZZ, et al. [The effect of Dang-Gui (Angelica sinensis) and its constituent ferulic acid on phagocytosis in mice (author's transl)]. Yao Xue Xue Bao 1981;16:411-4.
  23. Luo B, Li SC, Cui WY, et al. J Beijing Medical Uni 1987;19:419-22.
  24. Chen YC. [Experimental studies on the effects of danggui buxue decoction on IL-2 production of blood-deficient mice]. Zhongguo Zhong Yao Za Zhi 1994;19:739-41.
  25. Tao JY, Ruan YP, Mei QB. [Studies on the antiasthmatic action of ligustilide of dang-gui, Angelica sinensis (Oliv.) Diels]. Yao Xue Xue Bao 1984;19:561-5.
  26. Zhang YK, Wang HY, Wang SX. [The effect of the Chinese medical herbs Astragalus membranaceus and Angelica sinensis on 3 kinds of experimental nephritis]. Zhonghua Nei Ke Za Zhi 1986;25:222-5.
  27. Weng XC, Zhang P, Gong SS, et al. Effect of immuno-modulating agents on murine IL-2 production. Immunol Invest 1987;16:79-86.
  28. Ozaki Y. Antiinflammatory effect of tetramethylpyrazine and ferulic acid. Chem Pharm Bull (Tokyo) 1992;40:954-6.
  29. Wang SR, Guo ZQ, Liao JZ. [Experimental study on effects of 18 kinds of Chinese herbal medicine for synthesis of thromboxane A2 and PGI2]. Zhongguo Zhong Xi Yi Jie He Za Zhi 1993;13:167-70.
  30. Cho H, Mei B, Shang P, et al. Study of the gastrointestinal protective effects of polysaccharides from Angelica sinensis in rats. Planta Medica 2000;66:348-51.
  31. Ye YN, Liu ES, Shin VY. A mechanistic study of proliferation induced by Angelica sinensis in a normal gastric epithelial cell line. Biochem Pharmacol 2001;61:1439-48.
  32. Ye YN, Koo MW, Li Y, et al. Angelica sinensis modulates migration and proliferation of gastric epithelial cells. Life Sci 2001;68:961-8.
  33. Kobayashi S, Mimura Y, Kimura I. Antiproliferative effects of the traditional Chinese medicine shimotsu-to, its component cnidium rhizome and derived compounds on primary cultures of mouse aorta smooth muscle cells. Jap J Pharmacol 1992;60:397-401.
  34. Wang H,.Peng RX. [Sodium ferulate alleviated paracetamol-induced liver toxicity in mice]. Zhongguo Yao Li Xue Bao 1994;15:81-3.
  35. Hsieh MT, Lin YT, Lin YH. Radix Angelica sinensis extracts ameliorate scopolamine- and cycloheximide-induced amnesia, but not p-chloroamphetamine-induced amnesia in rats. Am J Chin Med 2000;28:263-72.
  36. Fu YF, Xia Y, Shi YP, et al. Jiangsu J Trad Chin Med 1988;9:15-6.
  37. Gao YM. J Lanzhou Medical College 1988;1.
  38. Liu MA, Qi CH, Yang JC, et al. Beijing J Trad Chin Med 1988;30-1.
  39. Xu JY, Li BX, Cheng SY. [Short-term effects of Angelica sinensis and nifedipine on chronic obstructive pulmonary disease in patients with pulmonary hypertension]. Zhongguo Zhong Xi Yi Jie He Za Zhi 1992;12:716-8.
  40. Hirata JD, Swiersz LM, Zell B, et al. Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertil Steril 1997;68:981-6.
  41. Lo AC, Chan K, Yeung JH, et al. Danggui (Angelica sinensis) affects the pharmacodynamics but not the pharmacokinetics of warfarin in rabbits. Eur J Drug Metab Pharmacokinet 1995;20:55-60.
  42. Page RL,.Lawrence JD. Potentiation of warfarin by dong quai. Pharmacotherapy 1999;19:870-6.
  43. Raman A LZSEea. Investigation of the effect of Angelica sinensis root extract on the proliferation of melanocytes in culture. J Ethnopharmacology54:165-70.
  44. Mills S, Bone K. Principles and Practice of Phytotherapy. 352. 2000. London, Churchill Livingstone.