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Dang Gui

Botanical Name: Angelica sinensis (Oliv.) Diels.
Pharmacopoeial Name: Angelicae radix.
Synonym: Angelica polymorpha Maxim. var sinensis Oliv.
Common Names: Dang gui, dong quai, tang kuei, tang kwei, Chinese angelica.
Note: The phonetic “dong quai” Romanization is not the correct Pinyin transliteration, which is “dang gui.” “Tang kuei” is the earlier Wade Giles transliteration, less used today.

herb characteristics

Family

Apiaceae.

Related Species

In East Asian commerce, several species may be traded as substitutes. Levisticum officinale Koch., or lovage, sometimes known as “European dang gui,” is a recorded adulterant, not a substitute.

Parts Used

Root; in East Asian traditional medicine, the head, body, and tail of the root are regarded as having different medicinal properties.

Common Forms

  • Dried:   Prepared root, smoke-dried; baked in wine.

  • Fluid Extract:   1:1 70% ethanol, according to the Pharmacopoeia of the People's Republic of China (PPRC) .

  • Standardized Extract:   Liquid or dry extracts may be standardized to ligustilide content (0.8%-1.0%) and to ferulic acid (0.05%-0.01%).

interactions review

Strategic Considerations

One of the better known herbs from the materia medica of classical Chinese medicine, dang gui (in traditional terms) supplements (nourishes) xue (blood), moves and dispels blood stasis, and regulates menses. It is also used for moistening dry conditions, dispersing swelling, and promoting the discharge of pus. 1 The herb has been incorporated into Western herbal medicine, primarily as a women's tonic herb for menstrual disorders and infertility. Dang gui use for menopausal issues is not currently supported by clinical trial data. 2 The herb is also used for its cardioprotective, hepatoprotective, and mild immunomodulatory effects. In the contemporary practice of Chinese medicine, it is widely used in many herbal formulae, as well as in combination with conventional treatments, such as myelosuppressive chemotherapy. 3

Much of the literature on dang gui is in Chinese-language journals, and many reports relate to formulae involving several ingredients, including dang gui. Few controlled trials are available, but there is a large body of traditional-use data, as well as a considerable number of uncontrolled trials in the East Asian medical literature. Many of the available studies, animal and human, involve parenteral administration, which cannot be readily extrapolated to oral administration used in the West. The herb is not referenced in official Western pharmacopoeias (although it was briefly in the USD in 1937) but has been official in the PPRC since 1977. The American Herbal Pharmacopoeia has produced a Western-oriented monograph, including a supplement on traditional Chinese usage, 4 and McKenna et al. 5 have reviewed much of the literature. Chen and Chen 6 have reviewed both the pharmacology and the traditional uses of the herb.

Interactions concerns about dang gui are largely the result of extrapolations from experimental pharmacological data of isolated ingredients, such as ferulic acid, ligustilide, or polysaccharide fractions of the herb, and usually stress the risks of concomitant use with anticoagulants. The traditional precautions and contraindications for dang gui, which include bleeding disorders, hemorrhagic disease, excessive menses, and first-trimester pregnancy, may be seen as equally appropriate in Western contexts.

Effects on Drug Metabolism and Bioavailability

Minimal data are available on the effects of dang gui on the different aspects of drug detoxification. Two Japanese studies are available. One screened a number of umbelliferous crude drugs in vitro for general cytochrome P450 (CYP450) inhibitory effects and found weak but measurable inhibition by dang gui, as well as other Angelica spp. After high-performance liquid chromatography analysis, the authors attributed this to the activity of a coumarin-derivative constituent, imperatorin. 7 A more specific in vitro study using rodent hepatic microsomes with various drug substrates found partial inhibition by dang gui extracts of CYP450 3A4, 2C9, and 2D6. 8 A Chinese study examined the effects of dang gui polysaccharide administration in normal and liver-damaged (by prednisolone) rodents and found that the herb fraction increased hepatic microsomal CYP450, glutathione- S-transferase, and reduced-glutathione content. 9 Pharmacokinetic interactions have not been reported, and in the case of warfarin have been ruled out as a mechanism of interaction 10 (see following discussion). Nonetheless, such effects seem theoretically possible, and further research is required to clarify the extent and significance of any potential pharmacokinetic interactions.

herb-drug interactions
Warfarin and Related Oral Vitamin K Antagonist Anticoagulants
Evidence: Warfarin (Coumadin, Marevan, Warfilone). Extrapolated, based on similar properties: Anisindione (Miradon), dicumarol, ethyl biscoumacetate (Tromexan), nicoumalone (acenocoumarol; Acitrom, Sintrom), phenindione (Dindevan), phenprocoumon (Jarsin, Marcumar); other drugs affecting hemostasis.
Minimal to Mild Adverse Interaction—Vigilance Necessary

Probability: 4. Plausible
Evidence Base: Mixed

Effect and Mechanism of Action

Addition of dang gui to previously stabilized warfarin anticoagulation regimens may require the dose of oral anticoagulant to be adjusted to prevent excessive anticoagulation. Only one report is available, suggesting the interaction is unlikely to be clinically significant. Dang gui has multiple effects on hemorheological parameters, the mechanisms of which are not fully elucidated, and whether this is a strict interaction or merely an additive common pharmacodynamic effect has not been established.

Research

The literature on hemorheological activities of dang gui is dominated by an emphasis on isolated constituents (e.g., ferulate, butylidenephthalide) with parenteral administration at high dose levels in animal and human studies. The trend of the data supports a possible antiplatelet effect, probably operating through arachidonic acid metabolism. 11-17 Other hemorheological effects were observed in a study using parenteral dang gui (200 mL aqueous solution, intravenous administration daily for 20 days), in a group of 50 patients after acute ischemic stroke, where administration resulted in significant reductions ( p<0.001) in platelet adhesion, red blood cell (RBC) and platelet electrophoresis times, erythrocyte sedimentation rate (ESR) and serum fibrinogen, and blood and plasma adhesion ratios. 18 Oral administration of an aqueous decoction of dang gui and the related Angelica acutilobawere given to six healthy patients, and whole-blood viscosity was reduced ( p<0.05) after 180 minutes compared with controls. 19

A study of warfarin and dang gui coadministration in rabbits investigated the effect of adding single-dose warfarin to animals pretreated with dang gui, as well as addition of dang gui to warfarin-stabilized animals, as measured by coagulation parameters. In the first case, adding warfarin to a dang gui pretreated group led to a ( p<0.05) lowering of prothrombin time (PT) compared with warfarin alone. Pharmacokinetic parameters of warfarin were not changed in the presence of dang gui pretreatment. Addition of dang gui to stable, warfarinized animals led to no significant change in PT or warfarin levels. In this study, warfarin was given at high dose levels subcutaneously, and a 2:1 extract of dang gui was given at 2 g/kg orally. The implication of this study appears to be that adding dang gui to stabilized warfarin is less problematic than adding drug to stabilized dang gui (in rabbits), although pharmacokinetic interactions were not observed. 10

Reports

In a single but much-cited report, a 46-year-old female warfarinized patient experienced an unexplained rise in international normalized ratio (INR) to 4.05. Investigations revealed no identifiable cause, and she was advised to discontinue her 5-mg warfarin dose for 24 hours. The INR remained elevated on retesting 1 week later. The patient admitted taking a herbal preparation (Nature's Way brand of dang gui), 565 mg twice daily. She was advised to stop the herb, and the INR declined to 3.41, then to 2.48 after 1 week. Concomitant medications included digoxin and furosemide. 20 Fugh-Berman and Ernst 21 evaluated the interaction as “likely,” scoring 8 of 10 on their report reliability scale.

Clinical Implications and Adaptations

The lack of reports of spontaneous bleeding associated with dang gui consumption alone, with only one report of the warfarin–dang gui interaction to date, suggests that concerns about the incidence and severity of the interaction are exaggerated. As always, self-prescription is a separate issue, and many warfarinized patients are poorly compliant with their monitoring test schedules. As a guideline, prescribing dang gui to warfarinized patients should generally be avoided unless there are compelling reasons for coadministration. In such cases, close monitoring of INR is required.

However, as is often the case from an integrative perspective, the potential interaction may be beneficial under specific circumstances. Dang gui has cardioprotective and thrombolytic effects that may be beneficial depending on the situation. 6,22 For example, patients receiving a typical 1 mg/day oral dose of Coumadin after temporary installation of vascular access ports/catheters for prevention of thrombosis at the catheter tip may benefit from the addition of dang gui, combined with natural antiplatelet and fibrinolytic agents, particularly if there are other indications for prescribing the herb. However, checking PT/INR weekly would be appropriate if coadministration is considered, because 1 mg Coumadin could affect PTs if circumstances altered (e.g., vitamin K deficiency).

Erythropoiesis-Stimulating Agents
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Acetaminophen
Cycloheximide, Scopolamine
Nifedipine
Oral Contraceptives and Related Estrogen-Containing and Synthetic Estrogen and Progesterone Analog Medications
Ouabain and Related Cardiac Glycosides and Antiarrhythmic Drugs
Citations
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