Angelica: A Comprehensive Reference
1. Identity and Botanical Classification
The term Angelica in the context of dietary supplements and herbal medicine refers primarily to two distinct species within the family Apiaceae (also known as Umbelliferae): Angelica sinensis (Oliv.) Diels, the Chinese species, and Angelica archangelica L., the European species. A third species, Angelica acutiloba, is used in Japan as a close substitute for A. sinensis. These are not the same plant: A. archangelica, often referred to as garden angelica or wild celery, is native to Europe, while A. sinensis, known as dong quai, is a staple in Traditional Chinese Medicine celebrated for its benefits in women's health. While both share some medicinal properties and uses, they are distinct species with different traditional applications and growing regions.
Angelica sinensis
Angelica sinensis, commonly known as dong quai or "female ginseng," is a herb belonging to the family Apiaceae, indigenous to China. It is the dry root of the umbelliferae plant Angelica sinensis (Oliv.) Diels. It grows as a perennial herbaceous plant at altitudes of 2,500 to 3,000 meters. A. sinensis is mainly produced in southeastern Gansu, followed by Yunnan, Sichuan, Shaanxi, Hubei, and other provinces. The drug material is known in Chinese as Dāng Guī (当归) or Danggui, and the official pharmaceutical name for the dried root is Radix Angelicae sinensis.
The dried root exhibits a light brown to brown coloration, characterized by longitudinal wrinkles and transverse lens-like perforations. Fried slices are typically round, oval, or irregular in shape, displaying a yellow-white to light brown hue with a flat surface that may feature cracks. A light brown cambium ring is present at the center, accompanied by several brown oil spots.
Angelica archangelica
Angelica archangelica, also known as garden angelica, is a biennial herbaceous species of the genus Angelica. It has a hollow stem carrying compound, alternate, yellowish-green leaves. It blooms during the summer, the seeds ripen in late summer, and then the plant dies. The flowers are greenish-white in color and small in size. It is a native herb of Western Asia, northern Europe, Iceland, Scotland, and Syria. Angelica is an herbaceous perennial that can reach a height of up to 2 meters. It grows out of a thick, turnip-shaped rootstock (rhizome), from which numerous thin (adventitious) roots, each up to 30 cm long, grow into the ground.
The scientific names are Angelica archangelica L. and the synonym Archangelica officinalis Hoffm. Common names include European angelica, Garden Angelica, Holy Ghost, Norwegian angelica, and Wild Celery. The quality of Angelicae radix is specified in the European Pharmacopoeia (Ph. Eur.).
Common Preparations and Dosage Forms
Both species are available in multiple forms. Dietary supplements and teas that contain dong quai are made from the roots of the plant. Several forms of the plant exist and dosages vary widely: crude root extract by decoction ranges from 3 to 15 g/day; while in combination, preparations of 75 mg to 500 mg may be taken up to 6 times a day. For A. archangelica, traditional doses of angelica dried root and rhizome range from 3 to 6 g/day (in divided doses). All portions of the plant can be used for pharmacological and culinary purposes, as several studies have shown, though the root is the primary medicinal component. A. sinensis has also been used to flavor liqueurs and confections.
2. Traditional and Historical Use
Traditional Chinese Medicine (Angelica sinensis)
Angelica sinensis (Apiaceae), the root of which is known in Chinese as Danggui, was first documented in Shennong Bencao Jing (Shennong's Materia Medica; 200–300 AD) and has been used as a blood tonic to treat menstrual disorders. Radix Angelicae sinensis (Danggui in Chinese), the dried root of Angelica sinensis (Oliv.) Diels, is a crude drug widely used in the alleviation of various disease syndromes in Traditional Chinese Medicine (TCM) for more than two thousand years.
It is a traditional medicinal and edible plant that has long been used for invigorating the blood, promoting circulation, lubricating the intestines, regulating menstruation, as well as relieving pain, treating female irregular menstruation and amenorrhea. Known in English as Chinese angelica root or dong quai, it has been used continuously for over 2,000 years and is the principal women's tonic in the Chinese tradition. It belongs to the category of Blood tonics in the Chinese Materia Medica.
In classical TCM practice, the root was divided anatomically for different therapeutic emphasis: the root is divided into three parts — head (most blood-tonifying), body (balanced), and tails (most blood-moving) — though most modern preparations use the whole root. The aromatic root is harvested in late autumn and dried by smoking. It has a slightly bittersweet, pungent taste and is processed into a strengthening tonic. In Traditional Chinese Medicine (TCM), dong quai is also used in the treatment of postpartum women: this strengthening tonic is intended to help women recover from the stresses of pregnancy and childbirth. It is also used in some postpartum mixtures as galactogogues in Taiwan.
Several hundred years ago, when the supply of Chinese angelica was scarce, the Japanese began to cultivate A. acutiloba, an angelica species indigenous to Japan, as a substitute. Dong quai is used in combination with other plant extracts in Chinese traditional medicine as an analgesic for rheumatism, an allergy suppressant, and in the treatment of menstrual disorders.
European Folk and Medical Traditions (Angelica archangelica)
Angelica archangelica has been used in European herbal medicine for over a thousand years. The name "angel," which also appears in the Latin genus name Angelica, refers to the legend that the medicinal plant was shown to people by an angel. The specific epithet archangelica reinforces this idea. According to legend, it was the Archangel Raphael who brought to the attention of a hermit the healing properties of the plant. Its name was derived from a monk's dream in which St. Michael the Archangel appeared, telling the monk what herb to use to help victims of the bubonic plague that was decimating Europe in 1665.
Across medieval Europe, angelica was worn as a charm to ward off disease and bad energy. In Scandinavia, the Saami people treated it as a sacred herb as early as the 12th century. Cultivated since the 10th century, A. archangelica became a staple in folk medicine for digestive support, respiratory health, and general vitality. In traditional Scandinavian folk medicine, it was known as "änglakälla," or angel's root, brewed into tonic wines for digestion.
The root, seed, leaf, and fruit have been used historically in Nordic folk medicine. Both in the Chinese and Indian systems of medicine, it is used for nervous disorders including anxiety, anorexia, migraine, and other cerebral diseases. When European colonists arrived in North America, they found many Indian tribes using American angelica in the same way as their own healers used the European species: to treat respiratory ailments, in particular tuberculosis.
ESCOP has recognized the following applications for Angelica archangelica, based on findings from long-term use in humans: dyspeptic complaints such as mild gastrointestinal spasms, sluggish digestion, flatulence, feeling of fullness, loss of appetite, and bronchitis.
3. Key Constituents and Active Compounds
Angelica sinensis
Over 70 compounds have been isolated and identified from Danggui. The main chemical constituents of Angelica roots include ferulic acid, Z-ligustilide, butylidenephthalide, and various polysaccharides. Over 70 compounds have been identified from Danggui, including essential oils such as ligustilide, butylphthalide, and senkyunolide A; phthalide dimers; organic acids and their esters such as ferulic acid and coniferyl ferulate; polyacetylenes; vitamins; and amino acids.
Compounds in dong quai include alkyl phthalides (ligustilides, angelicide, and butylphthalide), furanocoumarins (archangelicin, bergapten, and imperatorin), coumarins (angelol G and angelicone), terpenes (cadinene and carvacrol), phytosterols (beta-sitosterol and stigmasterol), organic acids (ferulic, succinic, and myristic), and an immune-stimulating polysaccharide.
Z-ligustilide, Z-butylidenephthalide, and ferulic acid are thought to be the most biologically active components in A. sinensis and are often used in quality control and pharmacokinetic studies of Danggui. It is thought that most of the potential benefits of A. sinensis come from ligustilide, a powerful compound that comprises approximately 1% of the plant and provides much of its strong fragrance.
The polysaccharide fraction is of particular pharmacological interest. Angelica sinensis polysaccharide (ASP) is a major ingredient in Angelica sinensis with significant bioactivities, such as antioxidant, antitumor, antiaging, antihepatotoxic, immunomodulatory, and neuroprotective effects. ASP is one of the main active ingredients of Angelica sinensis and has various pharmacological activities, including antitumor, antioxidant, immunomodulatory, hematopoietic, and hepatoprotective effects.
Angelica archangelica
The main characteristic constituents of A. archangelica root include the essential oil, containing mainly monoterpenes and smaller amounts of sesquiterpenes, coumarins such as prenylcoumarins and furanocoumarins, as well as various phenolic acids. The chief constituents of angelica are about one percent volatile oil, valeric acid, angelic acid, sugar, a bitter principle, and a peculiar resin called angelicin. It also contains selimone, archangelin, and oxypeucedanin. The most abundant furanocoumarins in the tincture of the fruits are imperatorin, xanthotoxin, isoimperatorin, oxypeucedanin, psoralen, and bergapten.
Fifteen coumarins have been isolated from a chloroform extract of the roots of Angelica archangelica L. subsp. archangelica (Apiaceae), including archangelicin, oxypeucedanin hydrate, bergapten, imperatorin, isoimperatorin, isopimpinellin, osthol, ostruthol, oxypeucedanin, phellopterin, psoralen, and xanthotoxin. Extraction with supercritical carbon dioxide yielded more than 200 compounds of A. archangelica in the extracted oil. The content of constituents depends on the origin, age, species, and extraction method. Notably, the coumarin content of A. archangelica roots can be elevated to 20- to 200-fold of the regular content due to fungal infection.
4. Mechanisms of Action
Anti-Inflammatory Mechanisms
Ferulic acid and isoferulic acid inhibit macrophage inflammatory protein-2 (MIP-2) production by murine macrophage RAW 264.7 cells, suggesting that these compounds contribute to the anti-inflammatory activity of A. sinensis. Z-ligustilide also shows anti-inflammatory effects, probably related to inhibition of TNF-α and NF-κB activities. A. sinensis suppresses NF-κB luciferase activity and decreases NO and PGE₂ production in lipopolysaccharide/IFN-γ-stimulated murine primary peritoneal macrophages. Ferulic acid and Z-ligustilide, two major compounds, decrease NF-κB luciferase activity, which may contribute to the anti-inflammatory activity.
Ferulic acid exerts anti-inflammatory effects through (1) the regulation of inflammatory cytokine levels; (2) modulation of signaling pathways such as NF-κB, MAPK, and JAK/STAT; (3) amelioration of oxidative stress; and (4) regulation of immune cell homeostasis. At the pharmacokinetic level, studies show that ferulic acid is rapidly absorbed but exhibits low bioavailability, mainly due to the influence of metabolic pathways and food matrix characteristics.
Cardiovascular and Cerebrovascular Mechanisms
The organic acids (ferulic acid), volatile oil (ligustilide, senkyunolide H, and butylidenephthalide), and polysaccharides in A. sinensis are the main chemical components that play a role in preventing cardiovascular and cerebrovascular diseases. Its protective effects are mainly related to regulating the expression levels of relevant enzymes, proteins, and genes; inhibiting or activating the autophagic function of cells; improving abnormal blood rheology; regulating oxidative stress response; reducing inflammatory reactions; and suppressing related cell apoptosis. A. sinensis has been shown to have significant effects on cardiovascular and cerebrovascular diseases, such as anti-atherosclerosis, regulation of blood glucose and blood lipids, inhibition of thrombosis, and improvement of cognitive impairment.
Hematopoietic Mechanisms
ASP has been proved to have beneficial effects in multiple disease models including cancer, leukemia, anemia, and inflammation. In studies on aplastic anemia, ASP demonstrated the ability to mitigate P38/MAPK-induced Bax-associated mitochondrial apoptosis, while also reducing the levels of activated Th17 cells and alleviating abnormal cytokine levels. The protective effect of A. sinensis and ASP on hematopoietic function lies in their ability to prevent apoptosis. In animal models of anemia of chronic disease, ASP treatment significantly reduced the production of proinflammatory cytokines IL-6 and TNF-α, and substantially increased serum erythropoietin (EPO) levels.
Estrogenic and Hormonal Activity
Results from studies evaluating dong quai's estrogenic effects have been conflicting, possibly due to differences in the preparations studied, and there is some data to suggest serotonergic activity. The evidence base suggests a complex, context-dependent hormonal profile rather than a simple estrogenic mechanism.
Coumarin-Mediated Neurological Mechanisms (A. archangelica)
In animal studies, a petroleum ether extract was found significant (P < 0.01) in doses of 5 and 10 mg/kg for anxiolytic-like effect. The extract was shown to contain multiple constituents, and non-polar coumarins were isolated: namely imperatorin (IM) and isoimperatorin (IIM). Animal studies suggest anticonvulsant, antidepressant/antianxiety, and antioxidant effects of angelica or its constituents; however, clinical trials are lacking to support therapeutic applications or recommend use for any indication.
5. Scientific Evidence by Area of Use
5.1 Menopausal Symptoms and Hot Flashes
By far the most popular use of Angelica species has been the use of Angelica sinensis in the treatment of menopausal complaints. Dong quai is widely used in the United States to treat hot flashes and other symptoms of menopause, despite a lack of clinical data.
The clinical evidence for dong quai as a stand-alone treatment for menopausal symptoms is weak. Despite its widespread use, there is very little clinical evidence to back up dong quai's efficacy in treating menopause symptoms. There were no significant changes in hot flashes or vaginal dryness between dong quai and a placebo in a trial of 71 women. Single clinical trials do not support the use of dong quai (Angelica sinensis L.) for improving menopausal symptoms.
When used in combination formulas, the picture is somewhat different: hot flashes and night sweats were dramatically decreased in two independent trials utilizing dong quai in combination with other herbs such as red clover, black cohosh, and chamomile. Three randomized controlled trials have examined the use of dong quai for perimenopausal symptoms and menstrual migraine. Overall vasomotor episode reduction was noted in 20% to 35% of patients in several studies, although another study failed to show any significant difference between dong quai and placebo. One study demonstrated a 56% reduction in menstrually associated migraine attacks.
Evidence characterization: Preliminary and inconsistent. Positive findings for combination products cannot be attributed to dong quai alone. Stand-alone clinical evidence does not support efficacy for menopausal hot flashes.
5.2 Hot Flashes in Men (Androgen Deprivation Therapy)
A randomized double-blind placebo-controlled trial was conducted to determine whether dong quai has a therapeutic benefit in treating hot flashes among prostate cancer patients receiving androgen deprivation therapy. The trial involved 22 men receiving luteinizing hormone-releasing hormone agonist therapy for prostate cancer with bothersome hot flashes. After recording a baseline log of the frequency, duration, and severity of daily hot flashes, patients were randomly assigned in a 1:1 ratio to receive daily placebo or dong quai for 3 months. Vasomotor and adverse events were recorded daily. Data from clinical trials of dong quai for menopausal symptoms are inconclusive. A small study failed to find efficacy of dong quai against hot flashes in men.
Evidence characterization: A single small (n=22) randomized controlled trial found no benefit. Evidence is insufficient to support this use.
5.3 Blood and Hematopoietic Conditions
Clinical data confirmed that the level of transfusion dependency and IL-17A were lower in A. sinensis users compared to non-users (p < 0.001) in a study examining aplastic anemia. However, the evidence for hematopoietic effects derives largely from preclinical (animal and in vitro) studies. ASP has various pharmacological activities, including antitumor, antioxidant, immunomodulatory, hematopoietic, and hepatoprotective effects. Recent studies have indicated an extraordinary antiaging role of ASP, which protected hematopoietic stem/progenitor cells (HSC/HPCs) against X-ray-irradiation-induced aging by inhibiting oxidative stress damage, alleviating DNA damage, and increasing telomerase activity.
Evidence characterization: Predominantly preclinical (in vitro and animal). Some clinical observational data in aplastic anemia exists, but rigorous large-scale human trials are lacking.
5.4 Gastrointestinal and Digestive Function (A. archangelica)
The ESCOP monograph recognizes therapeutic indications for angelica root including dyspeptic complaints such as mild gastrointestinal spasms, sluggish digestion, flatulence, feeling of fullness, loss of appetite, and bronchitis. These ESCOP applications are based on findings from long-term use in humans. A small clinical trial found no increase in blood pressure or heart rate during 8 weeks of leaf extract use.
Evidence characterization: Traditional use is well-documented and recognized by ESCOP. Controlled clinical trial data for gastrointestinal indications is limited; acceptance rests substantially on traditional use.
5.5 Cardiovascular Effects
Scientific reports on crude extracts and pure compounds and formulations of A. sinensis revealed a wide range of pharmacological activities, including anti-inflammatory activity, antifibrotic action, antispasmodic activity, antioxidant activities, and neuroprotective action, as well as cardio- and cerebrovascular effects. It is commonly used for the prevention and treatment of cardiovascular and cerebrovascular diseases in the elderly, especially in improving ischemic damage to the heart and brain, protecting vascular cells, and regulating inflammatory reactions.
Evidence characterization: Evidence is largely preclinical (in vitro and animal). Robust randomized human clinical trial data on cardiovascular outcomes are lacking.
5.6 Anxiety and Neurological Effects (A. archangelica)
Animal studies suggest anticonvulsant, antidepressant/antianxiety, and antioxidant effects of angelica or its constituents; however, clinical trials are lacking to support therapeutic applications or recommend use for any indication. The possibility of increased formation of amyloid-beta peptides exists with use of angelica.
Evidence characterization: Strictly preclinical at this time. No human clinical trials of adequate size or design are available to substantiate anxiolytic or neuroprotective claims for A. archangelica.
5.7 Anticancer Activity
Active compounds in the Angelica genus, such as coumarins, furanocoumarins, phthalides, and polysaccharides, exhibit anticancer properties through various mechanisms. Specific species, like A. archangelica and A. sinensis, have been traditionally used for their medicinal properties, and recent studies have suggested their potential use as anticancer agents. In animal and test-tube studies, A. sinensis extract kills glioblastoma cells, which is a form of aggressive brain cancer. However, this does not mean that taking an angelica root supplement can kill brain cancer in humans. In fact, this is unlikely, and much more research in humans is needed before A. sinensis can be considered a potential cancer treatment.
Evidence characterization: In vitro and animal data only. No clinical evidence supports anticancer use in humans.
6. Body Systems and Health Areas
- Reproductive / Endocrine system: Dong quai is used principally for menstrual irregularity, painful periods, scanty flow, blood-deficiency anemia, postnatal recovery, perimenopausal symptoms, and as a cornerstone in fertility prescribing.
- Cardiovascular / Hematological system: As one of the traditional Chinese medicinal materials for tonifying deficiency, A. sinensis not only has unique traditional medicinal effects and modern pharmacological activities, but also has rich nutrients and edible benefits, which has a good effect in the prevention and treatment of cardiovascular and cerebrovascular diseases in the elderly.
- Immune system: Major pharmacological effects of Danggui extract or its components include anti-inflammatory, anti-cancer, immunomodulatory, anti-cardiovascular, neuroprotective, anti-oxidative, anti-hepatotoxic, and renoprotective activities.
- Gastrointestinal system (A. archangelica): Traditionally used to support digestive function, gastrointestinal function, and to stimulate the appetite.
- Nervous system (A. archangelica): Animal studies, as noted above, suggest possible anxiolytic and anticonvulsant properties linked to coumarin constituents, though no clinical data yet confirm these effects.
- Respiratory system: The ESCOP monograph for angelica root includes bronchitis among its recognized therapeutic indications.
7. Dosage Forms and Reported Dosages
For Angelica sinensis: several forms of the plant exist and dosages vary widely: crude root extract by decoction ranges from 3 to 15 g/day; while in combination preparations, 75 mg to 500 mg may be taken up to 6 times a day.
For Angelica archangelica: clinical trials are lacking regarding dosage recommendations. Traditional doses of dried root and rhizome range from 3 to 6 g/day (in divided doses).
Many aspects associated with the use of the root are deemed problematical, such as identity, processing, amount and types of constituents, tradition of use in combination with other Chinese herbs, ethnicity of users, etc. Standardization of preparations across studies is inconsistent, making direct dose comparisons difficult.
8. Safety Considerations and Drug Interactions
Anticoagulant and Antiplatelet Interactions
A. sinensis may increase the anticoagulant effects of the drug warfarin (as it contains coumarins), and consequently may increase the risk of bleeding. Case reports exist of fever, gynecomastia, and bleeding with concurrent warfarin use. Although it is usually well tolerated in general use, it may increase the risk of bleeding in patients taking warfarin and antiplatelet drugs and cause photosensitivity reactions.
For A. archangelica: angelica contains furanocoumarins. Case reports of interactions with warfarin or other anticoagulant medicines are lacking; however, the related A. sinensis exhibits antiplatelet aggregating activity.
Photosensitivity
A risk of photosensitization exists with A. sinensis. Additionally, members of the Angelica genus contain furanocoumarins, which are the same compounds in grapefruit that may interact with many drugs, including certain cholesterol and anti-seizure medications. Furanocoumarins, such as bergapten and psoralen, have been widely studied for their photoactivated toxicity. The risk of phototoxicity should be correlated with the content of specific toxic furanocoumarins; in the case of A. sinensis, the risk appears to be limited. For A. archangelica, the presence of photosensitizing linear furanocoumarins in the root indicates that the plant parts should be used with caution during exposure to sunlight.
Pregnancy and Lactation
Uterine stimulant and relaxant activity have been reported with A. sinensis, while the related species Angelica archangelica L. was a reported abortifacient and affected the menstrual cycle. Relative contraindications exist in patients receiving warfarin, heparin, or other anticoagulant/antiplatelet therapy, in those with breast cancer, or in the first trimester of pregnancy. No data exist on the excretion of any components of dong quai into breastmilk or on the safety and efficacy of dong quai in nursing mothers or infants. Dong quai is best avoided during breastfeeding.
Hormone-Sensitive Conditions
Because it may exert weak estrogenic activity, A. sinensis should be used with extreme caution in patients with active, hormone-receptor-positive (ER+) cancers.
Photosensitizing Drug Combinations
Verteporfin: photosensitizing agents may enhance the photosensitizing effect of verteporfin. Monitor therapy. Each drug may increase the photosensitizing effect of the other; American ginseng and dong quai both increase anticoagulation — use caution and monitor.
Adulteration and Identification
The seeds (fruit) of A. archangelica are similar to, and sometimes confused with, water hemlock (Cicuta maculata), which is extremely toxic. Poisoning has been reported with high doses of angelica oils. Proper botanical identification of preparations is therefore of significant importance.
General Tolerability
Regarding adverse effects, A. sinensis presents rare and mild events, such as gastrointestinal disturbances, photosensitivity, and occasional allergic or cardiovascular reactions. Allergic dermatitis has been reported with A. archangelica, and photosensitization is possible.
9. Regulatory and Pharmacopeial Status
Three species of angelica are monographed separately in the Pharmacopoeia of the People's Republic of China: dong quai (the root of A. sinensis), and the root of Angelica dahurica. The quality of Angelicae radix (A. archangelica) is specified in the European Pharmacopoeia (Ph. Eur.). Angelica archangelica is widely used in traditional medicine worldwide and is mentioned in many pharmacopeias and medicinal systems. The ESCOP herbal monograph selects and summarizes scientific studies and textbooks regarding efficacy, dosage, and safety to support the therapeutic uses of angelica root.
References
Go back