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Oregano

Glossary, HerbsSuccess Chemistry Staff
oregano-healing.jpg

Oregano

is a close relative of the marjoram and applies as this also as a medicinal plant. With its mild-spicy taste, oregano plays an important role in the Mediterranean cuisine. Classically, this herb is found on pizza and in tomato sauce. But it also has a lot of other uses. Oregano blends well with fruity tomatoes, cucumbers, and salads. Also with egg dishes, sauces, potato, and tomato soup, this aromatic herb fits.

Oregano as a medicinal herb

Although oregano is usually known only as a kitchen herb, it finds in the folk medicine relatively much attention. Oregano can be used for a variety of ailments due to its containing ingredients.

Oregano was already known in antiquity and the Middle Ages as a herb with great healing power. Oregano was used to treat painful hemorrhoids. In gynecology, the medicinal herb was used to initiate the birth. Furthermore, oregano was in the Middle Ages as a tried and tested means to shield themselves from demons, witches and the devil. From oregano lentils in the house and incense with oregano promised the same effect as garlic used against vampires.

In old herbal books, oregano, as well as some oregano species commonly referred to as Wohlgemuth (Wolgemut) or Dosten. In the herbal book by Petri Andreae Matthioli, the herb was used for both internal and external applications. Oregano was recommended among other things with itching (application: Oreganobad), with tumors of the almonds (presumably almond inflammation) or with the Wundbehandlung. Oregano has also been used to treat gastrointestinal complaints, coughing or tracheal diseases. The herb was usually mixed with red wine or drunk as pressed juice.

Today, however, oregano is used for problems in the gastrointestinal tract. The tannins and bitter substances in the oregano have an anticonvulsant effect, thus helping with gastric and/or intestinal cramps as well as flatulence and casually stimulate the appetite.

The plant parts of the oregano, especially the leaves and the herb contain a variety of different active ingredients. The containing essential oils, tannins, and bitter substances have the following healing effect:

  • antibacterial

    1. carminative

    2. appetizing

    3. cough expectorant

    4. antifungal

    5. antioxidant

To relieve stomach and intestinal complaints or chronic bronchitis, oregano is usually taken in the form of tea. One teaspoon of dried cabbage or two teaspoons of fresh oregano is poured over with 250 to 300 ml of boiling water. The infusion is left covered for about 10 minutes and then drunk. Even with a bacterial cough and infestation of Candida fungi, Oreganotee can be drunk supportive.

externally, oregano is used in inflammatory skin problems, as the ingredients in the essential oil of oregano (especially phenols and carvacrol) are classified as antibacterial and anti-inflammatory. Oily ginger tinctures are used to treat greasy, blemished skin, which is used to dab the affected areas of the skin.

Oregano - Medicinal herb of the Mediterranean

Oregano is an indispensable part of the Mediterranean cuisine. In the West, it is almost exclusively associated with delicious dishes from Italian cuisine.

Oregano is not only used as a medicinal but also as a spice plant.

But also the people of the eastern Mediterranean know and love oregano. For example, anyone traveling to Turkey will come across this tasty herb again and again; as well as in Greece and Spain. Incidentally, in the Middle Ages, it was often used there for dyeing, for example, wool. But back to the present and to Italy, where Oregano has also been known for centuries and is prized for its unmistakable flavor. Pasta sauces are mainly prepared here. But also with lamb dishes and everything that has anything to do with tomatoes, oregano is often used for seasoning. In addition, it is indispensable for a real Italian pizza.

Where does oregano come from?

Oregano is not only widespread in the Mediterranean, but the herb also has its original home here. It belongs botanically to the family Lamiaceae. In Germany, oregano is also known by names such as "wild marjoram", "Dost", "Dorst" and "Wohlgemuth". The latter points to the healing properties associated with the condiment. It helps the digestive tract to the legs and relieves coughing. For a soothing tea, add one teaspoon of dried oregano to a one-quarter liter of boiling water and infuse for five minutes.

How is oregano used?

Herbs are very important in Italian cuisine. Without basil, parsley, sage, and oregano, Italian dishes are almost unthinkable. They are mainly used fresh in salads, in sauces for pasta dishes, for egg dishes and in the context of tomatoes. A classic example is "Insalata Caprese"; an appetizer consisting of tomatoes, mozzarella, and fresh basil. Oregano is often used in a dried form for meat dishes. Classically, the Italian mom will use it in lamb dishes; Oregano also goes well with pork and beef.

When is oregano available and what should you pay attention to when buying?

Oregano is grown today almost everywhere in the world and is therefore available all year round fresh in the supermarket, in the vegetable trade and at weekly markets. It is usually offered in pots. In addition, the herbs are also dried and rubbed. It then has a slightly changed, woody and intense taste. In fresh plants, make sure that the leaves do not hang limp and have no brown edge.

Grow oregano yourself

As long as you have a sunny spot in the garden, this spice herb can easily be grown by yourself. You can sow just as well as-as of May - buy also bought young plants. Those who prefer seeds should only lightly press the earth over them. Oregano is a so-called "light germ," so the seeds should not be buried too deep in the ground. Moderate, but regularly poured, there will soon be a rich harvest. Partly dry part of it for the winter months.

 

 

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Sage

Herbs, GlossarySuccess Chemistry Staff

Sage medicinal benefits 

With over 60 ingredients, sage combines the healing properties of eucalyptus, rosemary, wormwood & tea tree oil.. It is a popular Mediterranean herb and is known for its use in saltimbocca or entrecote. Sage is ideal for refining meat dishes of all kinds and pasta. If the aroma is too intense, you can fall back on the much milder young leaves. The healing effects of sage can be used, for example, in homemade cough syrup, sage cough sweets or tooth-care throat drops.

The true sage - Latin name Salvia officinalis - is considered with its disinfecting and astringent effect as one of the most important medicinal herbs and played a major role in ancient and Celtic mythology. The Egyptians also appreciated him very much. They gave their women sage juice to promote fertility. Perhaps the following advice comes from this: women should eat a raw sage leaf every time they walk the garden. Sage leaves are also an integral part of ancient medicine, the ancient Ayurveda. In the Middle Ages, the herb was considered a panacea and was mainly grown in monastery gardens.

Pharmacists and doctors at that time appreciated him especially as a wound treatment for wound cleansing and hemostasis. Already in the 6th-century monks brought the medicinal plant across the Alps in northern regions. Therefore, it is not surprising that at early mention the plant appears in the monastery plan of St. Gallen, the monk Strabo from the monastery Reichenau and Hildegard von Bingen. The herbal boom in the 1980s made sure that the forgotten herb gardens were recreated in many monasteries and opened to the public. Even in cottage gardens, Salvia officinalis is a traditional plant that must not be missed. Today, more and more people trust in herbal medicine, and so the herb finds application in many complaints. As a spice herb,

Origin of sage

The home of sage is the Mediterranean. But now you can find this herb and spice herb in many gardens, where it prefers a heat-loving plant full sun and light soil. He does not love waterlogging and too much fertilizer, on the other hand, he withstands drying times very well. As a heat-loving plant, however, it needs a winter shelter in rough locations, for example, brushwood. Wild it still grows in Italy, mainly on the Adriatic coast in sandy and calcareous areas. In addition to Salvia officinalis, there are numerous other species of sage, which are cultivated partly in the garden as ornamental plants. All sorts of sage belong to the family of the mint family and bloom in different colors. The true shows from May to July its approximately two inches long blue to purple flowers, which make an excellent bee pasture. The perennial, bushy plant grows up to 80 cm high and lightens easily if you do not prune it back after flowering. Striking are the elongated silvery-green and slightly felty leaves. They emanate an aromatic fragrance through the contained essential oils. The leaves also contain the manifold healing powers.

Special features of sage

Sage leaves have a sharp, dry and strong, slightly bitter taste. In the kitchen, they are therefore particularly suitable for high-fat meals. However, mainly sage is used as a medicinal herb. Its known active ingredients are essential oils that include thujone, borneol, cineole, and camphene among other things, the leaves are rich in tannins and bitter substances, terpenes and numerous flavonoids. For the bitter substances, it is above all the typical salvin. The amount and composition of these substances are highly dependent on climatic conditions and the harvest time, which is most ideal before flowering. Together, the ingredients have antibacterial, antiviral, fungicidal, astringent and antiseptic properties. Thujone is poisonous, therefore you should not consume sage tea or drops for a long time. The name Salvia comes from Latin and means salvation or healing. This says a lot about the broad effect of the plant. The medicinal herb is used for tea, tincture, drops, sage oil, sage wine, and powder; in the industry for throat sweets and pastilles. For the applications mainly the dried sage leaves are taken. To do this, cut off some stems before blooming, hang them up in tufts or lay them out to dry in layers not too thick in the shade. In the oven or in the Dehydrator you can also dry at a maximum of 40 degrees. After drying keep dark and cool. You can also buy dried sage leaves. Pay attention to the quality.

Sage as a medicinal herb - earlier and today

In natural medicine, the use of medicinal herbs has a long tradition. Even Hippocrates, Hildegard von Bingen, and Paracelsus - to name just the best known - recommended the use of sage in fever, colic, urinary tract disorders, loss of appetite, colds, dental disease and red dysentery. During the various plague epidemics, the herb also played a significant role. Thieves rubbed their bodies with a mixture of sage leaves, lavender, rosemary, and thyme to protect them against the pest and were able to plunder the houses of the dead without becoming infected. The medicinal herb was also used for cramps, itching, pneumonia, somnolence, digestive problems, and body aches. Old recipes recommend sage powder or fresh leaves for teeth and gums for cleansing and strengthening. As early as the 10th century, Arab doctors, scholars, and philosophers used sage tea with honey to enhance their mental abilities. As an essential sage oil, it has a disinfecting and antispasmodic effect. In addition, the oil is suitable for colds for inhalation. Due to the disinfecting effect sage leaves were burned for a long time as fumigants in the room of the seriously ill.

Even today, many of these recommendations are valid and medical research can largely confirm this ancient knowledge. The active ingredients actually provide relief from everyday problems. Naturally, the herb is used today in:

  • Gingival and oral mucosal inflammations

  • Colds and sore throat

  • Tonsillitis, pharynx, and laryngitis

  • heavy sweating

  • for wound healing

  • mild indigestion

  • bronchitis

  • Panting and smoker cough

  • rheumatism

  • headaches

  • Nervousness and weak nerves

  • for breastfeeding during lactation

  • thin, graying hair

  • skin problems

The best-known uses of sage are certainly inflammation in the mouth and throat and various dental diseases. For this, rinsing or gargling with sage tea or mouthwash is recommended. Even special ready-made salvia preparations can help with these complaints. Because sage has anti-inflammatory and antispasmodic properties, it is also often included in toothpaste and cough sweets. Known is the effect of sage tea in case of excessive sweating, especially during menopause. Sole tea is also helpful for girls during puberty and for women in menstrual disorders. Responsible for this are probably the contained tannins and terpenes.

Regular drinking of cold tea - 2-3 cups a day, but not more than four weeks, then take a break - inhibits sweat production. The tea can bring relief for indigestion. These include the irritable stomach syndrome, which can cause flatulence, cramps, pain, and loss of appetite. It is even believed, according to recent studies, that sage tea has an effect on the lowering of blood sugar levels. This would be ideal for diabetics. The antibacterial and anti-inflammatory effect of sage is ideal for wound healing and for bad and oily skin. Salvia bites from a strong decoction are recommended here. They have a calming, astringent and anti-inflammatory effect. In lactating women, sage tea prevents milk flow and should therefore not be consumed during breastfeeding. In the case of weaning, however, it can be helpful. Thin and graying hair regularly flushed with a strong broth, makes the hair stronger and gives it a nice dark color.

Even with greasy hair helps a flush with the broth. Seating baths with salvia or the daily intake of sage wine to support the nervous system, such as stress and excitement. The herb calms and brings serenity, at the same time it also stimulates and strengthens the circulation. In studies, even an anticarcinogenic effect of sage was found. The contained diterpenes are said to trigger the cell death of the tumor cells. Leukemia and lymph node cancers are being discussed. Like the Egyptians, the Englishman John Gerard found in the Middle Ages: "Sage is uniquely good for the head and brain and accelerates the nerves and the memory". A team from the Newcastle up Tyne Medical Plant Research Center did a study on this and the result confirmed this statement by Gerard.

The reason is an enzyme of sage, which inhibits the degradation of the messenger acetylcholine. In Alzheimer's disease, this messenger substance is broken down in the brain. It is now being researched which ingredients of sage are responsible for this and whether a drug can be developed from them. Studies have also observed the inhibitory effect on the herpes virus. Ritual fumigation with the purifying effect of medicinal herbs has always existed. Today, these fumigations are again increasingly carried out, for example, for cleaning rooms at home, after illnesses, significant changes in life or in agriculture, the stables.

How can you apply sage 

Applied internally, tea is the simplest remedy. It strengthens the resistance of the organism and the nervous system. Ideal for menopausal symptoms with palpitations, blood rush in the head and sweating. Add 2 teaspoons of dried sage leaves and bake with 1/4 l of boiling water. Let it rest for 10 minutes, strain. Depending on your taste you can add some honey or a splash of lemon juice. In case of sweating and indigestion drink cold.

A weekly sitz bath can contribute to mental health. Women also help a sitz bath in case of discharge or soreness in the genital area. For this, let 4 handfuls of dried sage leaves in about three liters of cold water overnight. Heat to boiling the next day, strain and place in the bath water (38-40 degrees). Bathing in it for 20 minutes. Sage wine can also strengthen the nerves. Add 80 g of dried sage leaves and strain for 10 days in 1 liter of sweet wine. Then drain through a cloth. Take 1 tablespoon after each meal.

The sage tincture is like tea against perspiration, diarrhea, and stomach upset. For this, 50 g of dried sage leaves are mixed with 1/2 liter of 50% alcohol in a bottle. Close and allow to shake for 10 days, shaking frequently. Then drain through a cloth and fill in a brown pharmacy bottle - possibly with a pipette. Take 30 drops of tincture 3 times a day for 1 tablespoon of water.

Sage envelopes can help with spotty skin. The herb regulates sebum production and fights bacteria. The envelopes can also help with wound healing. Add 2 tablespoons of dried sage leaves to 150 ml of boiling water, infuse for 20 minutes, strain. Soak a clean cotton cloth in the warm infusion, gently wring it out and place it on the wound. Envelopes can also be applied to the face for blemished facial skin or cotton swabs placed in the appropriate places. Leave for 20 minutes, then rinse with lukewarm water.

Ointment water helps with bleeding gums, it heals and strengthens the gums. To chop 6 fresh sage leaves small. Bring 1/2 liter of water and a pinch of salt to a boil and infuse the sage leaves. Allow to cool, pour through a fine sieve and squeeze the leaves well. After brushing, use as gargle water.

For gingivitis, chewing fresh sage leaves or rubbing in and rubbing with leafy pulp is recommended. Fresh sage leaves are also said to help with bad breath. For pressure points of dentures or braces repeated rubbing with fresh leaves can help.

The homemade sage syrup also helps with colds and is also taken by older children. To do this, boil 1 kg of sugar in 1 liter of water. Then add 4 handfuls of fresh sage leaves and 2 sliced bigotries. Run for two days in a cool place, strain and boil briefly again. Bottling hot and sealing well. For cold and sore throat, drink 1 tablespoon of syrup 3 times a day on 1 glass of warm water.

Beware of side effects!

In principle, internal applications with sage tea, tincture or oil should only be carried out for the duration of the symptoms. The active ingredient thujone can cause symptoms of intoxication if it is taken longer and in larger quantities. Signs of toxic effects include accelerated heartbeat, convulsions, nausea, dizziness and heat. External applications and use as spice are generally harmless. For pregnant women, infants and nursing mothers, the medicinal herb is in no form. Suckling tea, on the other hand, is a popular remedy for reducing milk flow. Allergic reactions occur sporadically.

Astragalus

Herbs, GlossarySuccess Chemistry Staff

INTRODUCTION

Astragalus root (Astragalus membranaceus and Astragalus

mongholicus) (Figs. 1 and 2; flowers are shown in Fig.

2) is one of the most important plant products used

in traditional Chinese medicine (TCM) for supporting

immune resistance ( ; wei qi) and energy production

( ; bu qi). Astragalus is also one of the most popular

ingredients in botanical dietary supplements for its

putative effect of supporting healthy immune function.

Despite the widespread use of this botanical among

TCM practitioners and its extensive use in botanical

supplements, there are few clinical trials supporting

its use, though those that are available are positive.

Numerous preclinical studies provide evidence for a

number of pharmacological effects that are consistent

with the traditional and modern use of astragalus.

BACKGROUND

Traditional and Modern Uses

In Asia, astragalus is commonly used according to both

its traditional Chinese medical indications as a general

tonifier and specifically for immune enhancement and for

modern biomedical indications such as immune, liver, and

cardiovascular support. It has been used for the prevention

of the common cold and upper respiratory tract infections

and is widely prescribed to children for prevention

of infectious disease, though formal clinical English language

studies regarding this use are lacking. In the West,

astragalus is primarily used as an immune modulator.

Astragalus potentiates recombinant interleukin-2 (rIL-2)

and recombinant interferon-1 and -2 (rIFN-1 and -2) immunotherapy

and by lowering the therapeutic thresholds,

may reduce the side effects normally associated with these

therapies. The data and opinion of those expert with the

use of the botanical suggest that astragalus is useful as a

complementary treatment during chemotherapy and radiation

therapy and in immune deficiency syndromes. There

is some modern evidence for its use in hepatitis and the

treatment of cardiovascular disease.

In TCM and Western clinical herbal medicine, astragalus

is most commonly used in combination with other

botanicals and is very seldom used as a single agent. There

are numerous studies of some of the classic combinations

of astragalus (e.g., astragalus and Angelica sinensis). These

have not been reviewed, but use of formulas is more consistent

with the use of the astragalus than with the use of

the herb alone according to traditional Chinese medical

principles.

CHEMISTRY AND PREPARATION OF PRODUCTS

The primary compounds of interest in astragalus are triterpenes,

polysaccharides, and flavonoids. The triterpene astragaloside

IV is a relatively unique marker for astragalus

species used in Chinese medicine. A variety of preparations

are utilized in clinical practice and in herbal supplements.

A number of preparations, including crude extracts,

isolated polysaccharides, and triterpene saponins,

have been subject to study and correlated with activity.

Clinically, in China and among some practitioners in the

United States, decoctions are frequently given. However,

due to the time required for cooking and the subsequent

smell and taste of Chinese herb preparations in general

(though astragalus is very agreeable), many consumers

and practitioners prefer crude powder or extract preparations

(capsules, tablets), freeze-dried granules, or liquid

extracts. Astragalus is also used as a relatively common

ingredient in soups, especially during winter months.

Polysaccharides (12–36 kD) have been most often

correlated with immune activity, while triterpene

saponins have been predominantly associated with cardiovascular

and hepatoprotective effects. Astragalus

polysaccharides are generally composed of a mixture of

D-glucose, D-galactose, and L-arabinose or D-glucose

alone. The glucose units appear to be primarily -(1,4)-

linked with periodic -(1,6)-linked branches (1,2). The

triterpene glycosides vary by position, number, and type

of sugar residues at positions 3, 6, and 25. Several of

these “astragalosides” (e.g., astragaloside IV; Fig. 3) are

composed of a single xylopyranosyl substituent at the 3-

position, which may or may not be acetylated. Others possess

either disaccharide or trisaccharide substituents (3–

5). Primary flavonoids of astragalus for which activity has

been reported include calycosin, formononetin (Fig. 3),

and daidzein (Fig. 3) and additionally include isorhamnetin,

kaempferol, and quercetin, among others (6).

PRECLINICAL STUDIES

Pharmacokinetics

Pharmacokinetic data available in English language publications

on astragalus, its crude extracts, or its constituents

are very limited. In the most detailed study to

date, the pharmacokinetics of a decoction of astragalus,

the preparation most used traditionally were investigated

in four models: four complement in silico, a cacao-2 intestinal

cell model, an animal, and a human volunteer

(n = 1). Intestinal absorption was demonstrated for several

flavonoids including calycosin and formononetin,

along with their aglycone metabolites in all four

models. Triterpene saponins, used as chemical markers

of astragalus (e.g., astragaloside I and IV) in the Pharmacopoeia

of the People’s Republic of China and the American

Herbal Pharmacopoeia, were lacking, likely due to

their low concentrations in the preparation. In the human

volunteer, nine flavonoids, including calycosin, formononetin,

and the isoflavone daidzein, were detected

Figure 2 Astragalus flowers. Source: Photo courtesy of Bill Brevoort, American

Herbal Pharmacopoeia.

in urine (7). In animal models (rats and dogs), astragaloside

IV, which has demonstrated cardioprotective activity,

showed moderate-to-fast elimination. The half-life in male

rats was from 67.2 to 98.1 minutes, in female rats 34.0 to

131.6 minutes, and was linear at the intravenous doses

given. The highest concentration of astragaloside IV was

found in the lungs and liver. Only 50% of the compound

was detected in urine and feces. Binding to plasma protein

was also linear at the concentration of 250–1000 ng/mL.

Slow systemic clearance of astragaloside IV occurred via

the liver at approximately 0.004 L/kg/min (8).

In another pharmacokinetic study, a two compartment,

first-order pharmacokinetic model was

used to describe the pharmacokinetics of intravenously administered

astragaloside IV. Systemic clearance of this

triterpene was reported as moderate and distribution into

peripheral tissues was limited (9).

Pharmacodynamics

A large percentage of research on astragalus has focused

on its immunostimulatory activity and its purported

ability to restore the activity of a suppressed immune

system. More recently, interest in its potential as a cardioprotective

agent has been shown. Reviews of a limited

number of clinical trials and preclinical data provide some

evidence for its usefulness in the prevention of the common

cold and as an adjunct to cancer therapies. There is

limited evidence to suggest a benefit to the cardiovascular

Astragalus 31

  • O

  • O

  • O

  • OH

  • OH

  • HO

  • O

  • H

  • OH

  • O

  • OH

  • OH

  • HO

  • OH

  • HO

  • O

  • O

  • OCH3

  • HO

  • O

  • OH

  • O

  • HO

  • Astragaloside IV

  • Formononetin

  • Daidzein

Figure 3 Some major constituents of Astragalus.

system, with improvement in clinical parameters associated

with angina, congestive heart failure, and acute myocardial

infarct. There is also some indication from animal

studies supporting its use in the treatment of hepatitis and

diabetes.

Immunomodulatory Effects

There are relatively strong preclinical data of pharmacological

mechanisms that provide support for the putative

immunomodulatory effects of astragalus.

Cancer

In a rat study, animals were pretreated orally for 50 days

with a low or high dose of astragalus extract (3.3 or

10 g/kg/day) prior to IP injection of doxorubicin (cumulative

dose of 12 mg/kg over a 2-week period). After 5 weeks

of the final injection of doxorubicin, a significant inhibition

of cardiac diastolic function was observed. This was

accompanied by ascites, catexia, decreased heart weight,

and increased mortality. Treatment with astragalus at both

doses significantly attenuated the negative effects of doxorubicin

on cardiac functions and ascites, while the high

dose also improved survival. This protective effective

was at least partially associated with the ability of astragalus

to attenuate changes in cardiac SERCA2a mRNA

expression (10).

A broad array of immunomodulatory effects has

been demonstrated in numerous preclinical studies that

suggest a substantial value of astragalus in conjunction

with conventional cancer therapies. The most relevant

of these was a series of investigations conducted

by researchers at the MD Anderson Cancer Center

that found that astragalus extract restored to normal

the immune response of patients’ mononuclear cells

that were grafted into rats immunocompromised by cyclophosphamide.

These researchers concluded that astragalus

and its polysaccharide fraction reversed the immunosuppressive

effect of cyclophosphamide (11–15). In

other studies, astragalus and its various fractions were

shown to stimulate macrophage phagocytosis (16) and

hematopoiesis (17).

One study reported on the gastroprotective effects

of astragalus extract (characterization not reported) in human

peritoneal mesothelial cells (HPMCs) subjected to

gastric cancer cell lines. Upon incubation with cancer cell

lines, apoptosis of the HPMC cells was observed. The astragalus

preparation, via regulation of Bcl-2 and Bax, partially

inhibited apoptosis. The authors interpreted these

findings as a potential that astragalus may slow down the

metastasis of the primary cancer and is therefore a potential

treatment for gastric cancer (18).

The ability of an astragalus fraction to potentiate the

effects of rIL-2 has been demonstrated in in vitro assays.

Lymphokine-activated killer (LAK) cells were treated with

a combination of the astragalus fraction and 100 units/mL

of IL-2. The combination therapy produced the same

amount of tumor-cell-killing activity as that generated

by 1000 units/mL of rIL-2 on its own, thus suggesting

that the astragalus fraction elicited a 10-fold potentiation

of rIL-2 in this in vitro model (19). These findings were

confirmed in a follow-up study by the MD Anderson researchers

using LAK cells from cancer and AIDS patients.

In this study, the cytotoxicity of a lower dose of 50 g/mL

of rIL-2 given with the astragalus fraction was comparable

to that of a higher dose of 500 g/mL of rIL-2 alone

against the Hs294t melanoma cell line of LAK cells. With

the combination, the effector-target cell ratio could be reduced

to one-half to obtain a level of cytotoxicity that was

equivalent to the use of rIL-2 alone. In addition, the astragalus

fraction was shown to increase the responsiveness

of peripheral blood lymphocytes that were not affected by

rIL-2. In this study, and in another by the same researchers,

it was concluded that the fraction potentiated the activity

of LAK cells and allowed for the reduction in rIL-2, thus

minimizing the toxicity of rIL-2 therapy (20). Other groups

of researchers reported almost identical findings (a 10-fold

potentiation) and concluded that astragalus is effective in

potentiating IL-2-generated LAK cell cytotoxicity in vitro

(21,22). Astragalus was also found to enhance the secretion

of tumor necrosis factor (TNF) from human peripheral

blood mononuclear cells (PBMCs). A polysaccharide

fraction (molecular weight 20,000–25,000) increased secretion

of TNF- and TNF- after isolation of adherent and

non adherent mononuclear cells from PBMCs (23).

Other investigations support the role of astragalus

polysaccharides as immunomodulating agents.

In an in vitro study, astragalus polysaccharides significantly

induced the proliferation of BALB/c mouse

splenocytes resulting in subsequent induction of interleukin

1 and tumor necrosis factor- and the activation

of murine macrophages. The researchers concluded

32 Upton

that astragalus had an intermediate-to-high affinity

for membrane immunoglobulin (Ig) of lymphocytes

(24).

Cardiovascular Effects

In animal studies, astragalus or its compounds were reported

to elicit antioxidant (25), mild hypotensive (26),

and both positive (27) (50–200 g/mL) and negative

(30 g/mL) inotropic activity (28). The inotropic activity

was reported to be due to the modulation of Na+–K+

ATPase in a manner similar to strophanthin K. Antioxidant

(29), calcium channel blocking (30), and fibrinolytic

activity (31) have been reported in in vitro studies. Astragaloside

IV was studied for potential cardioactivity.

Various effects have been reported. Intravenous administration

of astragaloside IV reduced the area of myocardial

infarct and reduced plasma creatine phosphokinase

release in dogs subjected to 3-hour ligation and increased

coronary blood flow in anesthetized dogs. In isolated rat

heart perfusion investigations, astragaloside IV significantly

improved (P < 0.01) postischemic heart function

and reduced creatine phosphokinase release from the myocardium.

In addition, coronary blood flow during baseline

perfusion and reperfusion in ischemic rat hearts was

increased, while reperfusion damage was decreased. This

activity was shown to be at least partially attributable to

coronary dilation via an increase in endothelium-derived

nitric oxide. Antioxidant activity via an increase in superoxide

dismutase (SOD) activity has also been reported for

astragalus and is considered to contribute to its cardioprotective

effects (32). Astragaloside IV was also shown

to significantly attenuate blood–brain barrier permeability

in a rat ischemia/reperfusion model (33).

Hepatoprotective Effects

Hepatoprotective effects against numerous hepatotoxic

agents (e.g., acetaminophen, carbon tetrachloride, and Escherichia

coli endotoxin) have been reported in both animal

and in vitro studies. In these experiments, improvement

in histological changes in hepatic tissue, including

fatty infiltration, vacuolar degeneration, and hepatocellular

necrosis, was reported. These effects may be associated

with saponin fractions (34). In one clinical study of

hepatitis B patients, concomitant use of astragalus with

lamivudine and -2b interferon showed greater efficacy

than with lamivudine alone (35).

Systemic Lupus Erythematosus

Astragalus was also studied for its ability to affect natural

killer (NK) cell activity, using an enzyme-release assay.

The NK cell activity of PBMCs from 28 patients with systemic

lupus erythematosus (SLE) was increased after in

vitro incubation with an undefined astragalus preparation.

Low levels of NK cell activity were correlated with

disease activity. PBMCs from patients with SLE had significantly

decreased NK cell activity as compared with

those from healthy donors. The extent of stimulation by

the astragalus preparation was related to the dose and

length of the preincubation period (36). Despite its use as

an immune-enhancing agent, which would normally be

considered contraindicated in autoimmune disorders, investigation

of astragalus may be warranted as evidence

suggests that it elicits significant anti-inflammatory activity

and improves ratios and function of T lymphocytes in

SLE (37).

Viral Infections

Prophylaxis against flu and modulation of endogenously

produced interferon have been reported in several animal

studies utilizing astragalus alone (6).

Other Effects

In a new line of investigation for astragalus, two triterpenes

(astragaloside II and isoastragaloside I) were

shown to alleviate insulin resistance and glucose intolerance

in mice. The two compounds selectively increased

adiponectin secretion on primary adipocytes and potentiated

the effects of the insulin-sensitizer rosiglitazone.

Chronic administration of the compounds (specific details

lacking) to both dietary and genetically obese mice

resulted in a significant increase in serum adiponectin, resulting

in an alleviation of hyperglycemia, glucose intolerance,

and insulin resistance. These effects were diminished

in mice lacking adiponectin (38).

One study showed that a liquid extract of astragalus

(2 g/mL/intravenous) retarded the progression of renal

fibrosis in a manner similar to the angiotensin-II-receptor

antagonist losartan. The study reported that like losartan,

astragalus decreased deposition of fibronectin and

type-I collagen by significantly reducing the expression of

transforming growth factor-1 and -smooth muscle actin

(P < 0.05) (39).

Astragalus was investigated for its potential effect

of reducing atopic dermatitis in mice. Using prednisolone

(3 mg/kg/day) as a comparator, an astragalus water extract

was administered orally at 100 mg/kg. Astragalus

significantly reduced the severity of chemically induced

inflammation (2,4-dinitrofluorobenzene) to a degree similar

to the comparator but, unlike prednisolone, did not

inhibit interleukin-4 production (40).

CLINICAL STUDIES

There are both English and Chinese language studies on

astragalus. As with much of the literature regarding Chinese

herbs, there are few clinical data of high methodological

quality. In addition, a positive publication bias

regarding Chinese literature has been reported (41), while

in primary American medical literature, a negative publication

bias against dietary supplement studies has been

reported (42).

Immunomodulatory Effects

Cancer

Among modern herbal practitioners, astragalus is recommended

as an immune supportive botanical in conjunction

with conventional chemo and radiation therapies for

cancer. There is a common belief and some clinical and

preclinical evidence that astragalus both reduces side effects

associated with conventional cancer therapies and

can potentiate the effects of certain therapies. The available

evidence is not strong enough to recommend astragalus

as a standard part of conventional cancer care. However,

Astragalus 33

its demonstrated safety, lack of negative interaction with

conventional therapies, and its putative benefit in building,

preserving, and restoring immunocompetency before

and after conventional therapies warrant specific study.

There is also potential for use of both oral and injectable

preparations, the latter of which are not approved in North

America but are widely used throughout Asia.

In one clinical study, an astragalus drip (20 mL in

250 mL saline solution daily for 84 days) was administered

to cancer patients (n = 60). Compared with the control

group (no astragalus), those in the astragalus group

showed a slower rate of tumor progression, a lower rate

of reduction in peripheral leukocytes and platelets, reduction

in suppressor CD8s, improved CD4/CD8 ratios,

increased IgG and IgM, and better Karnofsky scores (43).

In addition to its use alone, both as a primary treatment

and as an adjunct to conventional cancer therapies,

astragalus is most often combined with other similar acting

immune-enhancing plants. A number of randomized

prospective clinical studies of cancer patients were conducted

using a combination of astragalus and ligustrum

(Ligustrum lucidum) (undisclosed quantities) with positive

results, such as mortality reduction in breast and lung

cancer patients (44). These effects, of course, must be considered

to be due to the cumulative effects of the two

botanicals and cannot be presumed to occur with astragalus

alone but are more consistent with the manner in

which astragalus is used in TCM.

An early clinical trial reported that 53 cases of

chronic leukopenia responded favorably to an astragalus

extract (1:1; 2 mL daily intramuscularly for 1–2 weeks).

Improvements in symptoms and white blood cell counts

were observed, but specific data were lacking (34).

Cardiovascular Effects

Various cardioactive properties have been reported for astragalus,

and astragalus is widely used in the treatment of

both chronic and acute cardiovascular disease in China.

In one study, 92 patients with ischemic heart disease were

given an unidentified preparation of astragalus. Marked

relief from angina pectoris and other improvements as

measured by electrocardiogram (ECG) and impedance

cardiogram were reported. Improvement in the ECG index

was reported as 82.6%. Overall improvement was significant

as compared with the control group (P<0.05) (45).

A similar result in cardiac performance was reported by

other groups of researchers. In one study, 43 patients were

hospitalized within 36 hours of acute myocardial infarct.

After administration of an astragalus preparation (undefined

profile), the ratio of pre ejection period/left ventricular

ejection time was decreased, the antioxidant activity of

SOD of red blood cells was increased, and the lipid peroxidation

content of plasma was reduced (46). In another experiment,

20 patients with angina pectoris were given an

undefined astragalus preparation. Cardiac output, as measured

by Doppler echocardiogram, increased from 5.09 °æ

0.21 to 5.95 °æ 0.18 L/min 2 weeks after administration

of astragalus (P < 0.01). In this study, neither improvement

in left ventricular diastolic function nor inhibition of

adenosine triphosphate was observed (47). Intravenous

administration of astragalus (undefined preparation) was

reported to significantly shorten the duration of ventricular

late potentials in cardiac patients (39.8 °æ 3.3 ms vs.

44.5 °æ 5.9 ms; P < 0.01) (48).

In another investigation, astragaloside IV (intravenous;

unspecified amount) was given to patients with

congestive heart failure for 2 weeks. Improvement in

symptoms such as tightness in the chest, difficult breathing,

and reduced exercise capacity were reported. Radionuclide

ventriculography showed that left ventricular

modeling improved and left ventricular end-diastolic and

left ventricular end-systolic volume diminished significantly.

The authors concluded that astragaloside IV is an

effective positive inotropic agent (49), an action supported

by others (27).

Hepatoprotective Effects

In China, astragalus is widely used in the treatment of

chronic hepatitis where reductions in elevated liver enzymes

and improvements in symptoms in humans have

been reported. This activity is stated to be associated with

polysaccharides that increase interferon production (35).

Viral Infections

According to one English language review of the Chinese

literature, a prophylactic effect against the common cold

was reported in an epidemiological study in China involving

1000 subjects. Administration of astragalus, given either

orally or as a nasal spray, reportedly decreased the

incidence of disease and shortened cold duration. Studies

exploring this protective effect found that oral administration

of the preparation to subjects for 2 weeks enhanced

the induction of interferon by peripheral white blood cells.

Levels of IgA and IgG antibodies in nasal secretions were

reported to be increased following 2 months of treatment

(34). The effect of astragalus on the induction of interferon

was studied in a placebo-controlled study involving 28

people. Fourteen volunteers were given an extract equivalent

to 8 g of dried root per day and the rest were given

placebos. Blood samples were drawn before treatment,

then 2 weeks and 2 months after treatment. Interferon

production by leukocytes was statistically increased after

both time periods (P < 0.01) in the astragalus group but

not the control group (50). In another study, astragalus

was shown to potentiate the effects of interferon (rIFN-1)

in patients with chronic cervicitis (51).

Dosages

Crude root: 9–30 g daily as a decoction (52).

Decoction: 0.5–1 L daily.

SAFETY PROFILE

Side Effects

None cited in the literature.

Contraindications

None cited in the literature.

Precautions

There is some evidence to suggest that astragalus and its

putative anti-inflammatory effects are beneficial in those

with autoimmune conditions such as lupus. However, astragalus

should be used cautiously for the treatment of

34 Upton

autoimmune diseases or in conjunction with immunosuppressive

therapies. Because immunostimulating polysaccharides

may stimulate histamine release, allergic symptoms

may be aggravated by the use of astragalus. This,

however, has not been reported in the literature or from

clinical use. According to the principles of TCM, astragalus

should not be used during acute infectious conditions

unless under the care of a qualified TCM practitioner.

Interactions

Both positive and negative interactions may occur. Astragalus

potentiates the effects of acyclovir (53); IL-2, -20,

-21; and rIFN-1 and -2 therapies (50,51). Because of its immuno promoting

effects, astragalus may be incompatible

with immunosuppressive agents in general.

Pregnancy, Mutagenicity, and Reproductive Toxicity

According to one review, astragalus is reported to have no

mutagenic effects (54).

Lactation

Based on an authoritative review of the available pharmacologic

and toxicologic literature, no limitation is to be

expected (6,34,54).

Carcinogenicity

Studies suggest an anticarcinogenic activity.

Influence on Driving

Based on the available pharmacologic and toxicologic literature,

no limitation is to be expected (6,34,54).

Overdose and Treatment

Specific data are lacking.

Toxicology

Based on a review of the available data and the experience

of modern practitioners, astragalus can be considered

a very safe herb even when taken within its large

dosage range. Investigations of specific fractions including

flavonoids, polysaccharide, and triterpene similarly

show little toxicity (14,34,54).

Regulatory Status

In the United States, astragalus is regulated as a dietary

supplement.

CONCLUSIONS

Astragalus is one of the most frequently used herbal

medicines throughout Asia and is a very popular botanical

used in western herbal supplements. In China, astragalus

is used for a myriad of purposes relating to its

high regard as a strengthening tonifier, immune modulator,

anti-inflammatory, and anti-hepatotoxic. In the West,

astragalus figures prominently in immune supportive formulas.

Despite its popularity, there are few clinical trials

regarding its use. There is some evidence to support

the oral administration of astragalus for the prevention of

colds and upper respiratory infections, and as an adjunct

to conventional cancer therapies. These are very common

indications for which astragalus is applied by herbal practitioners.

For its use in cancer therapies, there are no definitive

guidelines. The modern experience of practitioners

together with the limited clinical and preclinical data

pointing to an immunomodulatory effect suggests that

there may be some value for these indications, including

the concomitant use of astragalus to reduce doxorubicininduced

immune suppression. However, more specific investigation

in this area is needed.

Regarding its putative immunomodulating effects,

the following mechanisms of action have been proposed:

restoration of immune function, increased stem cell generation

of blood cells and platelets, lymphocyte proliferation,

rise in numbers of antibody-producing spleen cells,

potentiation of rIL-2 and rIFN-1 and -2 immunotherapy,

enhancement of phagocytic activity by macrophages and

leukocytes, and increased cytotoxicity by NK cells.

Potential benefits to cardiovascular health, including

relief from angina and congestive heart failure and

improvement in clinical parameters following acute myocardial

infarct, have been reported. Limited animal studies

suggest that astragalus enhances coronary blood flow,

may potentiate the release of nitric oxide, and potentiates

the effects of endogenous antioxidant systems (e.g., SOD).

In Asia, astragalus is also used in conjunction with

conventional medical treatments for hepatitis. Both animal

and in vitro studies offer support for such treatment.

As in the use of astragalus in cancer therapies, further

clinical trials are required.

Though methodologically sound clinical trials for

astragalus are generally lacking, natural health practitioners

have a generally high regard for its use as a prophylactic

against infectious disease and for its ability to build,

maintain, and restore immunocompetency when used as

a part of conventional cancer therapies. In addition to the

very limited number of formal clinical studies that are

available in English language sources, the published medical

literature on astragalus has to be considered cautiously,

as a number of the supporting studies utilize injectable

preparations of isolated fractions that are not consistent

with the oral use of astragalus supplements. Still, the existing

data do support many of the traditional uses for

which astragalus has been employed for centuries.

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Dong Quai

HerbsSuccess Chemistry Staff

The root of dang gui (Angelica sinensis; also known as

dong quai; Fig. 1) is one of the primary botanicals used

in traditional Chinese medicine (TCM) for the treatment

of gynecological and circulatory conditions.

primary use is to both build and promote the movement

of blood, and on the basis of these actions it is utilized for

a myriad of conditions. Despite its widespread use among

practitioners of TCM, there have been few clinical studies

regarding its efficacy, although preclinical data support

many of these traditional uses as well as suggest benefit

for numerous other uses.

Traditional and Modern Uses Dang gui grows at high altitudes in comparatively cold,

damp, mountainous regions in China and other parts of

East Asia.

The plant is a fragrant perennial that has smooth

purplish stems and bears umbrella-shaped clusters (umbels)

of white flowers that grow to approximately 3 ft

in height. Dang gui produces winged fruits in July and

September. In the earliest known herbal text of China, the

Divine Husbandman’s Classic of the Materia Medica (Shen

Nong Ben Cao Jing), dang gui is described as a herb to

“supplement nature” (1). In the monumental 52-volume

Compendium of Materia Medica (Ben Cao Gang Mu), written

by Li Shizhen in the 16th century, dozens of uses for

dang gui were elaborated. These included the following:

to tonify the five major viscera, especially the heart; to generate

flesh; to stop headache, back pain, menstrual pain,

toothache, and pain associated with the “belt channel”

(dai mai); to treat a wide range of skin sores and rashes;

and to correct menstrual problems such as irregular menstruation,

amenorrhea, and dysmenorrhea (2).

Modern research has focused on the use of dang

gui for its ability to enhance circulation and oxygenation

in hypoxic conditions specifically in regard to brain and

cardiovascular effects. Despite the widespread popularity

and use of dang gui in gynecology, there is a lack of

research in modern English language journals regarding

this use, though some data suggest estrogenic and both

uterine relaxant and uterine stimulatory activity, depending

on the fraction studied. A number of studies report

on the ability of dang gui to promote the healing of tissues,

specifically in ulcerative colitis and gastric ulcers,

and other studies have focused on its anticancer and hepatoprotective

effects, among others.

Chemistry and Preparation of Products

The primary analytes of interest in dang gui are the Zalkylphthalides,

most notably ligustilide (Fig. 2), low- and

high-molecular-weight polysaccharides, and ferulic acid

(Fig. 2). The alkylphthalides are present in the essential

oil and are strongly aromatic. Both the crude extract and

individual compounds have been correlated with biological

activity (see preclinical studies; clinical studies). The

crude extract has been associated with positive human

clinical effects for the treatment of chronic obstructive pulmonary

disease (COPD) and COPD with hypertension,

increasing blood volume in postischemic patients, and

decreasing platelet aggregation (3). The alkylphthalides

and ferulic acid inhibit platelet aggregation and the formation

of platelet thromboxane A2 (4–6) and elicit in vitro

spasmolytic activity, increase coronary blood flow, slightly

decrease myocardial contractility, and markedly prolong

the effective refractory period (7). Total extracts have also

been associated with hepatoprotective effects. Thus dang

gui is utilized in portal hypertension and veno-occlusive

disease. At least part of this activity is associated with

the demonstrated antioxidant activity of ligustilide, ferulic

acid, and polysaccharides (8–10), as well as the ability

of dang gui to promote hepatic microcirculation. In human

clinical trials both an aqueous extract and ligustilide have

been found to be effective in treating dysmenorrhea (11).

Dang gui polysaccharides stimulate hematopoiesis and,

along with ferulic acid, elicit immunomodulatory activity

(e.g., increased phagocytosis) (12,13). Ligustilide and ferulic

acid elicit a strong uterine spasmolytic effect (14–17).

All of these actions are consistent with the use of dang gui

in traditional Chinese medicine.

Investigations of polysaccharides derived from

dang gui, specifically in conjunction with their potential

immunomodulatory effects have been conducted. The

polysaccharides, named A. sinensis polysaccharide fractions

(APF 1,APF2,APF3) and crude angelica polysaccharide

consist of rhamnose, galacturonic acid, glucose, galactose,

mannose, and arabinose in various ratios (18,19).

In TCM, the roots of dang gui are commonly prepared

as a tea, extract, syrup, tablet, or capsule. In supplement

form, dang gui occurs predominantly in tablets

and capsules, and occasionally in tinctures. As with the

majority of Chinese herbs, dang gui is most often used in

combination with other botanicals and is predominantly

featured in formulas for promoting healthy gynecological

and cardiovascular systems and for a healthy liver.

Different portions of the roots are used for different indications.

The whole roots are said to “harmonize” the

Whole dang gui (Angelica sinensis) roots.

blood; the dang gui root bodies (dang gui tou; ) are

used to build and nourish the blood and are commonly

included in soups for convalescence and blood deficiency;

the tails (dang gui wei; ) are predominantly used to

“break the blood” and prevent and treat abnormal blood

stagnation.

Pharmacokinetics

There are limited data on the pharmacokinetics of some

of the compounds contained within dang gui. In a study

of the bioavailability of ferulic acid in humans (n = 5), the

peak time for maximal urinary excretion of ferulic acid

following the consumption of 360 to 728 g tomatoes (providing

approximately 21 to 44 mg ferulic acid) was 7 to

9 hours (20). A considerable proportion of ferulic acid was

excreted as glucuronide in all subjects. The recovery of

ferulic acid in the urine, on the basis of total free ferulic

acid and feruloyl glucuronide excreted, was 11% to 25% of

that ingested. The bioavailability of ferulic acid from beer

is consistent with the uptake of ferulic acid from other

dietary sources, such as tomatoes (21). Urinary and biliary

metabolites of ferulic acid were primarily glucuronic

acid and glycine conjugates of ferulic acid and vanillic

acid. Major constituents of dang gui.

model and suggest that ferulic acid is rapidly and almost

completely absorbed from the intestinal tract (23). It has

also been reported that ferulic acid crosses the blood–brain

barrier, although in very low concentrations (24). The major

metabolites of ferulic acid are nontoxic and water soluble,

being excreted through the urine and bile as free acids

and acid conjugates.

PRECLINICAL STUDIES

Pharmacodynamics

Dang gui is one of the most widely used of all Chinese

botanicals. Historically and in modern Chinese medicine,

it has been primarily used as a general blood tonic for the

TCM diagnosis of blood deficiency, a syndrome closely

related, but not exactly analogous or limited, to anemia.

Dang gui has also been used for a myriad of gynecological

indications, although there has been very little research

done in this regard in English language journals. More

recently, pharmacological research has focused on the potential

of constituents of dang gui to elicit cardiovascular,

hematopoietic, hepatoprotective, antioxidant, antispasmodic,

and immunomodulatory effects. Chinese botanicals

are most often used in multi-ingredient formulas

rather than as single agents. Therefore, there are very few

clinical trials on dang gui alone, although numerous preclinical

studies exist. Due to the lack of primary English

language literature, it is difficult to adequately access or

adequately review the available data by non-Chinese language

readers. Another difficulty in reviewing the available

studies is that many of the investigations are of disease

patterns that are unique to TCM and do not have

well-defined corresponding Western diagnoses, or viceversa;

studies are conducted for indications not synonymous

with TCM indications. While the TCM findings are

relevant to TCM practitioners, their importance may be ignored

or even criticized by non-TCM practitioners. Study

of non-TCM indications often is conducted for purposes

of modern drug discovery and therefore can be criticized

on different grounds. Lastly, it has been reported that up

to 99% of studies presented in the Chinese medical literature

show results favoring test intervention, suggesting

the potential for a positive publication bias and hence the

need for caution in interpreting the available data (25).

Conversely, publication bias against dietary supplement

research in the primary medical literature of the United

States has been reported and may similarly limit a critical

review of investigations of herbal products (26).

The bioactive compounds most studied in dang gui

are phthalides, polysaccharides, and ferulic acid. Studies

using these compounds have reported a number of therapeutic

effects, some of which are consistent with the use

of dang gui in TCM and some of which are not. The contribution

of ferulic acid to the therapeutic effect of dang

gui is unlikely given its low concentration in crude dang

gui (0.05–0.09%). The compounds used in pharmacological

studies are often administered at doses exceeding those

available from typical dosages of dang gui root preparations.

While these data are presented, it is not possible to

extrapolate results from such studies to clinical efficacy

of orally administered crude drug products; hence, the

reported findings must be evaluated critically.

Cardiovascular and Hemorheological Effects

Clinically, dang gui is widely used for the treatment of cardiovascular

disease, specifically conditions that can benefit

from enhanced circulation and a decrease in platelet

aggregation. Preclinical studies using dang gui and some

of its constituents suggest actions and mechanisms by

which it may exert a cardiovascular effect. These include

stimulation of circulation, platelet aggregation inhibition,

decrease in myocardial oxygen consumption, and vasorelaxation

(measured as a decrease in vascular resistance;

see also effects on smooth muscle).

A number of animal studies and in vitro assays support

some of the putative cardiovascular effects of dang

gui. These include an increase in myocardial perfusion,

decrease in myocardial oxygen consumption, increase in

blood flow, decrease in vascular resistance, and inhibition

of platelet aggregation, ventricular fibrillation, and

arrhythmias (3). However, a direct extrapolation of these

findings to humans cannot be made without confirmatory

human studies. A review of the activity of sodium ferulate

reported that it both inhibits platelet aggregation and

elicits a thrombolytic activity in vitro and in vivo. These effects

were due to inhibition of cyclooxygenase and thromboxane

A2 synthase with improvements in blood viscosity,

reduction in the concentration of plasma fibrinogen,

and increase in coronary perfusion. Additional cardiovascular

effects reported include reduction of cholesterol

biosynthesis and lowering of triglycerides, improvements

in myocardial oxygen consumption, and antiarrhythmic,

antioxidant, and antiatherogenic activity (24).

Hepatoprotective Effects

A number of preclinical studies indicate that dang gui,

dang gui polysaccharides, ferulic acid, and sodium ferulate

have antioxidant effects that can protect the liver

against damage due to chemically induced toxicity. Part

of this action is due to the ability of dang gui polysaccharides

to reduce the levels of nitric oxide (24.6%), serum

alanine aminotransferase (40.8%), and serum glutathione

S-transferase (18.4%) in animals with acetaminophen induced

or carbon tetrachloride-induced liver damage

(8,9,27,28).

Gynecological Effects

Dang gui is one of the most important herbal medicines in

TCM for the treatment of menstrual disorders, especially

when used in combination with other botanicals. It has

traditionally been used to treat conditions associated with

the TCM diagnosis of “blood stasis” and “blood vacuity,”

which can be correlated with Western syndromes such

as amenorrhea, dysmenorrhea, endometriosis, uterine fibroids,

and certain forms of infertility. Its efficacy appears

to have been demonstrated over the 750-year history of its

use for these indications and its continued, and apparent,

successful use by modern practitioners of TCM. However,

there are few studies substantiating these effects (11,29),

and those that are available lack methodological rigor.

Using ELISA-type immunoassays of two steroidregulated

proteins, presenelin-2 and prostate-specific antigen,

in breast carcinoma cell line BT-474, researchers reported

that dang gui extract showed “weak” estrogen and

androgen antagonistic effects of 50% and 71% blocking activity,

respectively, and no progestational activity (29). In

contrast to these findings, another group of researchers

found no estrogen receptor binding, cell proliferation, or

progestin activity of an aqueous-ethanol extract of dang

gui (30).

A study of ovariectomized rats showed that an extract

of dang gui (300 mg/kg SC; 1% ligustilide) resulted

in a thickening of the luminal epithelium suggesting a

estrogenic activity, but one much lower than comparison

with estradiol. The extract also suppressed luteinizing

hormone secretion. The researchers considered ligustilide

to be the active compound on the basis of previous in vitro

research they conducted (31). Several preclinical studies

have investigated the estrogenicity of dang gui or ferulic

acid, with mixed, but largely negative, results. Some in

vitro assays have reported that dang gui extract exhibited

a significant dose-dependent inhibition of estrogen receptor

binding, indicating that it competed with estradiol

for receptor sites (32). In the same study, dang gui extract

dose-dependently induced reporter gene expression in

estrogen-sensitive rat uterine leiomyoma cells, suggesting

a potentially proliferative effect on these cells. However,

when tested in conjunction with the maximum stimulatory

dose of estradiol, the extract inhibited estradiolinduced

reporter gene expression, suggesting the possibility

that dang gui may act as an estrogen antagonist when

in the presence of physiological levels of estradiol. Another

group of researchers reported similar findings (33).

Effects on Smooth Muscle

Dang gui and its constituents have been shown to relax

the smooth muscle tissue of the vascular system, trachea,

intestines, and uterus. The spasmolytic effects of dang

gui on trachea and uterine tissues are consistent with

TCM indications. While the mechanism of the relaxant

action has not been fully elucidated, preclinical studies

suggest that it may be due, in part, to histamine receptor

blocking activity, calcium ion channel effects, or modulation

of cholinergic receptors. Both relaxing and stimulating

effects on uterine tissue have been reported, with

various constituents eliciting different actions. The therapeutic

relevance of in vitro findings to humans is unknown

given the lack of clinical evidence. Ex vivo studies

demonstrate that ligustilide and butylidenephthalide

isolated from the volatile oil of dang gui exhibit a strong

spasmolytic effect on isolated uteri (34,35). Ligustilide was

shown to relax early pregnant and nonpregnant uteri of

experimental animals (34). Ligustilide and butylidenephthalide

showed an inhibitory effect on prostaglandin F2-,

oxytocin-, or acetylcholine-induced contraction of nonpregnant

rat uteri (14,36). This could explain the spasmolytic

effect of the volatile oil. Other studies indicated

that the observed spasmolytic effect may be due to an

effect on calcium channels (14,37). Three of the available

studies reviewed found that ferulic acid elicited a uterine

spasmolytic effect. At oral doses of 300 to 1000 mg/kg

and IV doses of 30 to 300 mg/kg, ferulic acid inhibited

spontaneous uterine contraction in rats (16,17). The inhibitory

effect of IV ferulic acid was not blocked by either

propranolol or by cimetidine and it strongly inhibited the

uterine contraction induced by oxytocin (0.3 unit/kg), but

not that induced by acetylcholine (0.1 mg/kg) or serotonin

(10 g/kg). It was suggested that the uterine relaxant effect

of ferulic acid is partially due to the oxytocin receptor

system rather than its inhibitory effect on prostaglandin

biosynthesis (38). Another study, however, suggested that

ferulic acid may not be responsible for the spasmolytic

effect of dang gui, since its content in raw material is low

(approximately 0.03% to 0.06%) (39).

Hematopoietic Effects

One of the traditional applications of dang gui in TCM

is its use in the treatment of “blood vacuity,” which

closely, but not completely, corresponds to aWestern medical

diagnosis of anemia. Limited clinical and preclinical

data support this use. One proposed mechanism of action

is its reported effect in stimulating hematopoiesis.

These actions appear to be primarily associated with the

polysaccharide fraction (13,40). One study demonstrated

the hematopoietic effects to at least partially be associated

with proliferation of bone marrow mononuclear cells

through signal transduction pathways (e.g., MAPK/ERK

pathway) (41).

Antioxidant Effects

There have been numerous studies demonstrating an antioxidant

effect of dang gui and its constituents. Much of

these have focused on the antioxidant activity of ferulic

acid, which is well known for its ability to prevent lipid

peroxidation, inhibit superoxide anion radical formation,

scavenge free radicals, and protect against radiation damage

(42–44). Dang gui contains only trace amounts of ferulic

acid, so these in vitro findings cannot be extrapolated

to the use of crude dang gui preparations. There are, however,

animal studies showing that dang gui polysaccharides

have a protective effect against chemically induced

ulcerative colitis and inflammation. In one study, dang

gui polysaccharides elicited anti-inflammatory effects in

the gastrointestinal mucosa through inhibition of neutrophil

infiltration in the stomach (45). In another study,

dang gui polysaccharides (5 mg and 10 mg/mL in drinking

water) attenuated colonic lesions caused by oxidative

damage induced by 2,4-dinitrobenzene sulfonic acid in

rats in a dose-dependent manner. This action was associated

with a preservation of endogenous glutathione levels.

Other studies reported tissue-healing effects of dang

gui to be associated with ornithine carboxylase activity,

c-Myc protein expression, and epidermal growth factormediated

pathway (27,46). A follow-up study by the same

group of researchers showed that crude extract of dang gui

(50 mg/kg PO) significantly accelerated the healing of gastric

ulcers in animals and showed an anti-angiogenic activity

and a quicker restoration of mucosal synthesis and

mucosal cell proliferation (47).

Studies suggest that the antioxidant activity of dang

gui may reduce ischemia–reperfusion induced injury

(48,49), ameliorate cognitive dysfunction associated with

postischemic brain damage (49), and inhibit the damage

associated with aggregation of amyloid- peptide, suggesting

a possible use of dang gui in Alzheimer’s. These

effects were reported to be correlated with both ferulic

acid and Z-ligustilide (50).

Other studies show that dang gui provides antioxidant

protection against free radical induction of rat

adrenal medulla (PC12) cell lines (51) and suppressed

radiation-induced expression of tumor necrosis factor-

and tumor growth factor--1 (52), and prevented

doxorubicin-induced cardiotoxicity, without decreasing

the antitumor activity of the drug (53).

Wound-Healing Effects

In addition to the beneficial effects of dang gui’s

antioxidant activity on tissues noted earlier, specific

wound-healing properties have been reported. One

group of researchers found that a crude extract of dang

gui (characterization and dosage not available) significantly

accelerated epithelial cell proliferation in wounds

(27,46,54). The activity was reportedly associated with an

increase in DNA synthesis and epidermal growth factor

mRNA expression. The same researchers observed direct

wound-healing effects of dang gui crude extract, with

activity associated with increased ornithine carboxylase

activity and increased c-Myc expression. Another study

found that dang gui prevented bleomycin-induced acute

injury to rat lungs. Alveolitis and the production of malondialdehyde

were all reduced (P < 0.01 or P < 0.001), suggesting

immunomodulatory and antioxidant effects (55).

Immunomodulatory Effects and Potential

Anticancer Activity

Limited animal and in vitro studies have reported on

specific immunomodulatory effects of dang gui, including

stimulation of phagocytic activity and interleukin-2

production, and an anti-inflammatory effect. There is evidence

to suggest that the polysaccharide fraction of dang

gui may contribute to these effects. However, there is no

clinical evidence supporting these effects, and there appears

to be no direct correlation betweenTCMuse of dang

gui and immunomodulatory activity (56–58).

A new direction in investigation of the use of dang

gui is for its potential anticancer activity. Ligustilide has

been shown to have direct cytotoxic activity against several

human and animal cell lines (59–61). In the absence of

clinical and directly applicable toxicological investigation,

little emphasis should be placed on these in vitro findings.

There have, however, been a number of animal studies

suggesting immunomodulatory and anticancer activity.

In one study, n-butylidenephthalide suppressed growth

of subcutaneous rat and human brain tumors, reduced

tumor volume, and significantly prolonged survival in

treated rats. This activity was reported to be due to an

induction of cell cycle arrest and apoptosis (62). Polysaccharides

have similarly been shown to inhibit growth of

murine tumors (S180, EAC, L1210) in vivo, resulting in a

prolonged survival of treated animals. In vitro, dang gui

polysaccharides were shown to inhibit the metastasis of

human hepatocellular cancer cell lines (63).

A variety of immunomodulatory activities have

been reported for dang gui polysaccharides, including

enhanced macrophage and T cell numbers, increased

production of interleukin and interferon, improved

CD4/CD8 ratios, and a general regulation of Th1- and

Th2-related cytokines (18). Other actions reported for

polysaccharides include release of nitric oxide from

peritoneal macrophages and enhanced cellular lysosomal

enzyme activity (64,65).

Effects on Bone Cells

Dang gui is traditionally used in formulas for bone

and tendon injuries. A recent study investigated the

212 Upton

pharmacology behind this indication by testing the in

vitro effects of a 1% aqueous extract of dang gui on human

osteoprecursor cells. Cells were incubated for five

days in medium with (12.5–1000 g/mL) and without

the extract. Compared to untreated control cell cultures,

cell proliferation was enhanced at extract concentrations

less than 125 g/mL (P < 0.05), whereas it was inhibited

at concentrations greater than 250 g/mL (P < 0.05

at 1 mg/mL). Protein secretion in osteoprecursor cells

and type-I collagen synthesis were significantly increased

(P < 0.05) (66).

dong quai CLINICAL STUDIES

The clinical data regarding the use of dang gui alone are

scarce and of poor methodological quality.

Cardiovascular and Hemorheological Effects

One study reported that 0.08 g/day/IV of sodium ferulate

relieved symptoms of angina pectoris after three

to seven days of treatment (24). Limited clinical studies

have investigated the use of dang gui for the treatment

of patients with acute ischemic stroke or COPD with pulmonary

hypertension. Results provide fairly weak evidence

that dang gui exerts hypotensive and cardioprotective

effects. In general, the study design of the available

reports was poor and the patient populations extremely

limited.

One study looked at the effects of dang gui in 60

patients with COPD (67). In the dang gui group, levels of

blood endothelin-1, angiotensin II, endogenous digitalislike

factor, mean pulmonary arterial pressure, and pulmonary

vascular resistance were decreased significantly

(P < 0.05 or P < 0.01) compared to those in the controls

(20 °æ 6%, 36 °æ 9%, 38 °æ 11%, 17 °æ 5%, and 27 °æ 8%,

respectively). Another study showed that dang gui decreased

the mean pulmonary arterial pressure in patients

with COPD without changing blood pressure and heart

rate, suggesting a vasodilatory effect on pulmonary vessels

without effect on systemic circulation (3).

In another study, it was suggested that dang gui

and dextran exhibited positive effects on neurological and

hemorheological symptoms in patients recovering from

stroke (68). However, no control group was included,

and so any claimed effects are questionable. Other clinical

studies with very small numbers of patients (11,69)

have reported on an ability of dang gui to decrease blood

viscosity, an effect consistent with its traditional use. While

this effect may be real, the mechanisms by which this may

occur and the constituents involved have not been well

articulated.

Hepatoprotective Effects

There is some evidence to suggest that dang gui and its

constituents can decrease portal hypertension in patients

with liver cirrhosis without affecting systemic hemodynamics.

This use is consistent with the traditional actions

of dang gui in improving circulation, because portal hypertension

is thought to be due to the obstruction of hepatic

microcirculation (70,71).

Hormonal Effects and Effects on Menopausal Symptoms

Because of the putative effects of dang gui in gynecological

imbalances, various studies have investigated its

potential for eliciting hormonal effects. In one human

study (72), one of the few double-blind, placebo-controlled

trials with dang gui, no statistically significant differences

in endometrial thickness, vaginal cell maturation, or

menopausal symptoms were observed between subjects

taking dang gui and those taking placebo. This contrasts

with a study of ovariectomized rats which showed that an

extract of dang gui (300 mg/kg SC;1%ligustilide) resulted

in a thickening of the luminal epithelium suggesting estrogenic

activity, but one much lower than comparison with

estradiol (see gynecological effects).

Analgesic Effects

Two uncontrolled clinical trials were found that addressed

the traditional Chinese use of dang gui as an analgesic for

pain due to “blood stasis”; both used injectable preparations.

In one, an ethanol extract was administered (intramuscularly)

on alternate days for a total of 20 doses into

the pterygoideus externus of 50 patients with temporomandibular

joint syndrome. A 90% cure rate was claimed

(73). Thirty cases of refractory interspinal ligament injury

were treated by local injection of 2 mL of 5% or 10% dang

gui twice weekly for two to three weeks. Twenty-four

(80%) of these patients reported a disappearance of pain,

no tenderness, and the ability to work as usual; four (13%)

patients reported alleviation of pain; two (7%) reported

no improvement (74). These uses are consistent with the

traditional use of dang gui in TCM. However, the effects

of injectable preparations cannot be extrapolated to oral

use of dang gui.

Dosages

Crude herb: 6 to 12 g daily to be prepared as a decoction.

Fluid extract (1:1): 3 to 5 mL three times daily (75).

SAFETY PROFILE

Side Effects

On the basis of a review of the available traditional and

scientific data, dang gui is a very safe herb with a low

probability of side effects when used within its normal

dosage range. One review article that claimed to cover

200 reports on dang gui pharmacology stated that dang

gui had no major side effects (35). Individual case reports

regarding the potential of dang gui to promote bleeding

have been prepared.

Contraindications

On the basis of a review of the available literature and the

experience of practitioners, dang gui is contraindicated

prior to surgery and, generally speaking, in those with

bleeding disorders.

Precautions

Precautions regarding the use of dang gui and other botanicals

used in traditional systems of medicine must be differentiated

between those recognized in the scientific literature

and those recognized traditionally. There is evidence

suggesting an anticoagulant effect for dang gui, and there

Dong Quai 213

are two published reports on its ability to enhance the

effects of chronic treatment with warfarin (see interactions).

A few unpublished case reports suggest that high

doses or chronic administration of dang gui alone during

pregnancy may be associated with miscarriage. There are

also anecdotal reports of administration of dang gui alone

causing increased blood flow during menses (R.U., personal

communication). Therefore, patients should consult

with a qualified health care professional prior to using

dang gui if they have bleeding disorders, are using anticoagulant

medications, or wish to use it during menses

or in the first trimester of pregnancy. It must, however, be

noted that in TCM, dang gui is specifically indicated for

certain bleeding disorders that are due to an underlying

diagnosis of blood stasis and in certain cases of threatened

miscarriage. For such uses, dang gui must be used according

to TCM principles under the guidance of a qualified

TCM practitioner.

Interactions

Two reports are available suggesting that dang gui can enhance

the effects of the anticoagulant warfarin. According

to one of these, a 46-year-old woman with atrial fibrillation

who had been stabilized on warfarin for almost two

years (5 mg daily) consumed a dang gui product concurrently

for four weeks (565–1130 mg daily). She experienced

a greater than twofold elevation in prothrombin

time (from 16.2 to 27 sec) and international normalized

ratio (from 2.3 to 4.9). No other cause for this increase

could be determined. Within one month of discontinuing

dang gui use, coagulation values returned to acceptable

levels (76).

Ananimal study investigated the interaction of dang

gui and a single dose or a steady-state dose of warfarin

(77). Six rabbits were administered a single dose of warfarin

(2 mg/kg SC). Seven days later, the same animals

were given an aqueous extract of dang gui (2 g/kg PO,

twice of a 2 g/mL extract daily) for three days, after which

they were again given a single dose of warfarin. Plasma

warfarin concentrations were measured at intervals up to

72 hour after each warfarin dose, and prothrombin time

was measured daily during dang gui treatment and after

the warfarin doses. Mean prothrombin time did not

change significantly during the dang gui treatment period.

However, when measured after coadministration of dang

gui and warfarin, prothrombin time was significantly lowered

at 24, 36, and 48 hours compared to that with warfarin

treatment alone (P < 0.05 or P < 0.01). No significant

variations in the single dose pharmacokinetic parameters

of warfarin were observed after treatment with

dang gui. Hence, the mechanism of decrease in prothrombin

time could not be correlated to the pharmacokinetics

of warfarin. Another group of six rabbits was given 0.6

mg/kg of warfarin SC daily for seven days; a steadystate

plasma concentration was achieved after day 4. On

days 4, 5, and 6, the rabbits were treated as above with

dang gui. Mean prothrombin time was again significantly

increased after coadministration with dang gui and two

rabbits died at days 6 and 7 after the dang gui treatment

had begun. Plasma warfarin levels did not change after

dang gui treatment. The authors suggested that these results

indicate that precautionary advice should be given

to patients who medicate with dang gui or its products

while on chronic treatment with warfarin. Another

study reported that dang gui acted synergistically with

aspirin (24).

General enhancement of cytochrome P450 isoforms

has been reported for both water (CYP2D6 AND 3A)

and ethanol extracts (CYP2D6) of dang gui in animal

models (78).

One study reported that dang gui might enhance

the antitumor effect of cyclophosphamide in mice with

transplanted tumors (79).

Pregnancy, Mutagenicity, and Reproductive Toxicity

Because of its blood-moving properties, dang gui should

be used in pregnancy only under the supervised care of

a qualified health professional. According to TCM practice,

dang gui is used in combination with other herbs in

various stages of pregnancy (29). Formula traditionally

used in pregnancy are prescribed within the context of

specific diagnoses in which the use of dang gui in pregnancy

is clearly indicated. In the West, dang gui is often

used alone out of this traditional medical context. Because

of this, several Western sources consider dang gui to be

contraindicated in pregnancy. Data regarding the effect of

dang gui preparations on the fetus are lacking.

Lactation

There are three unpublished case reports of a rash in infants

of lactating mothers who were taking dang gui. The

rashes reportedly resolved upon discontinuation of the

preparation by the mother. Specific details regarding

the preparations used were lacking (Romm, August 1,

2002, oral communication to AHP). Dang gui is a member

of the botanical family Apiaceae, a group of plants that

contain many types of photoreactive compounds known

to cause rashes.

Carcinogenicity

Data regarding the effects of dang gui in relationship to

carcinogenicity are mixed with both tumorigenic and antitumorigenic

activity reported. Antitumor activity due to

an induction of cell cycle arrest and apoptosis has been

reported for ligustilide (62). Polysaccharides have been

shown to inhibit growth of murine tumors (S180, EAC,

L1210) in vivo. This was accompanied by a prolonged

survival of animals and an inhibition of metastasis in vitro

(63). Another animal study identified a possible antitumor

effect of dang gui applied to mice with Ehrlich ascites tumors

(80). Regarding the potential effects of dang gui on

estrogen-positive tumors the data are mixed. One in vitro

assay found that dang gui stimulated the growth of MCF-

7 breast cancer cell lines 16-fold, with no measurable effect

on estrogen receptors (81), while another found a possible

antitumor effect in T-47D and MCF-7 cell lines (82). Data

regarding the potential estrogenic effects of dang gui have

been mixed.

Influence on Driving

On the basis of the experience of modern herbal practitioners,

no negative effects are to be expected.

Overdose

On the basis of the available literature, its use as a “food”

ingredient in soups, and the experience of modern herbal

practitioners, dang gui appears to be safe when used at

recommended doses.

Treatment of Overdose

No data available.

Toxicology

The following lethal dose (LD50) values have been reported

for dang gui extract (8:1 or 16:1), 100 g/kg PO in

rats (83,84); dang gui aqueous extract, 100 g/kg IV in mice

(85); dang gui 50% ethanol extract, greater than 40 g/kg

PO in mice (86); dang gui total acids, 1.05°æ0.49 g/kg IP in

mice (87). The LD50 of ferulic acid IV in mice was reported

to be 856.6 mg/kg, (16) and that of ligustilide, approximately

410 mg/kg IP (88). In a review of the toxicology

literature on dang gui, it was reported that IV injection

of the volatile fraction of dang gui could cause kidney

degeneration (76).

REGULATORY STATUS

Regulated as a dietary supplement (USC 1994).

CONCLUSIONS

Dang gui is one of the most important herbal drugs in

TCM, primarily being used for blood tonification and the

treatment of gynecological disorders. More recently, interest

has focused on dang gui’s possible cardiovascular, hepatoprotective,

hematopoietic, antioxidant, antispasmodic,

and immunomodulatory effects. Despite its long tradition

of use and current widespread clinical utility, there has

been very little clinical work verifying the therapeutic efficacy

of dang gui when used alone, primarily due to the

fact that in TCM, botanicals are generally used in combinations

rather than as single agents.

On the basis of the literature available and keeping

many of its limitations for an English readership in

mind, there is limited clinical support for the use of dang

gui alone for the following indications: pulmonary artery

and portal hypertension, acute ischemic stroke, dysmenorrhea,

infertility, and pain due to injury or trauma. The

use of dang gui for most of these indications is consistent

with TCM. One trial on menopausal symptoms found no

effect of dang gui on hormonal activity. Most of the trials

available are of poor methodological quality.

Clinical and preclinical studies provide some

support for a wide variety of actions of dang gui.

These include the promotion of circulation, vasodilation/

relaxation, and the inhibition of platelet aggregation,

all of which are consistent with the “blood quickening”

properties ascribed to dang gui in TCM. Similarly, the

hematopoietic effect of dang gui is consistent with its use

in TCM to “nourish blood.” Its smooth muscle (uterus,

vessels, trachea) relaxant effects are consistent with its use

for dysmenorrhea, asthma, and coughing. Dang gui may

relax or stimulate the uterus depending on a variety of

factors. In general, the volatile oil fraction appears to be

a uterine relaxant, while the nonvolatile constituents appear

to stimulate contractions. There is some support for

the traditional use of dang gui as an analgesic and vulnerary.

The radiation protective effect of dang gui in animals

is most likely due to its antioxidant activity. Assays for an

estrogenic effect of dang gui have had mixed, but largely

negative, results. The relevance of many of these actions

to the therapeutic use of dang gui in humans has not yet

been demonstrated.