Success Chemistry

Discover who you are | Become unforgettable

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.

REFERENCES

1. Huang QS, Lu GB, Guo JH. Studies on the polysaccharides of

Astragalus membranaceus. Yao Xue Tong Bao 1981; 16(18):58.

2. Huang QS, Lu GB, Guo JH. Studies on the polysaccharides

of “huang qi” Astragalus mongolicus. Yao Xue Xue Bao 1982;

17(3):200–206.

3. Cao ZZ, Yu JH, Gan LX, et al. The structure of astramembrangenin.

Hua Xue Xue Bao 1983; 41(12):1137–1145.

4. Cao ZZ, Yu JH, Gan LX, et al. The structure of astramembrannins.

Hua Xue Xue Bao 1985; 43(6):581–585.

5. Kitagawa I,Wang HK, Yoshikawa M. Saponin and sapogenol

XXXVII: chemical constituents of astragali radix, the root of

Astragalus membranaceus Bunge, astragalosides VII and VIII.

Chem Pharm Bull 1983; 31(2):716–722.

6. Upton R. ed. Astragalus Root. Monograph. Santa Cruz, CA:

American Herbal Pharmacopoeia, 1999.

7. Xu F, Zhang Y, Xiao SY, et al. Absorption and metabolism of

astragali radix decoction: in silico, in vitro, and a case study

in vivo. Drug Metab Dispos 2006; 34:913–924.

Astragalus 35

8. Zhang WD, Zhang C, Liu RH, et al. Preclinical pharmacokinetics

and tissue distribution of a natural cardioprotective

agent astragaloside IV in rats and dogs. Life Sci 2006; 79:808–

815.

9. Zhang WD, Zhang C, Liu RH, et al. Determination of astragaloside

IV, a natural product with cardioactivity, in plasma,

urine and other biological samples by HPLC coupled with

tandem mass spectrometry. J Chromatogra B 2005; 822;170–

177.

10. Su D, Li HY, Yan HR, et al. Astragalus improved cardiac

function of adriamycin-injured rat hearts by upregulation of

SERCA2a expression. Am J Chin Med 2009; 37(3):519–529.

11. Chu DT, Wong WL, Mavligit GM. Immunotherapy with

Chinese medicinal herbs I: immune restoration of local

xenogeneic graft-versus-host reaction in cancer patients by

fractionated Astragalus membranaceus in vitro. J Clin Lab

Immunol 1988; 25(3):119–123.

12. Chu DT, Wong WL, Mavligit GM. Immunotherapy with

Chinese medicinal herbs II: reversal of cyclophosphamideinduced

immune suppression by administration of fractionated

Astragalus membranaceus in vivo. J Clin Lab Immunol

1988; 25:125–129.

13. Chu DT, Sun Y, Lin JR. Immune restoration of local xenogeneic

graft-versus-host reaction in cancer patients in vitro

and reversal of cyclophosphamide-induced immune suppression

in the rat in vivo by fractionated Astragalus

membranaceus. Chin J Integr Trad West Med 1989; 9(6):

326–354.

14. Chu DT, Lepe-Zuniga J,Wong WL, et al. Fractionated extract

of Astragalus membranaceus, a Chinese medicinal herb, potentiates

LAK cell cytotoxicity generated by low dose of recombinant

interleukin-2. J Clin Lab Immunol 1988; 26(3):183–187.

15. Shimizu N, Tomoda M, Kanari M, et al.An acidic polysaccharide

having activity on the reticuloendothelial system from

the root of Astragalus mongholicus. Chem Pharm Bull 1991;

39(11):2969–2972.

16. Tomoda M, Shimuzu N, Ohara N, et al.Areticuloendothelial

system-activating glycan from the roots of Astragalus membranaceus.

Phytochemistry 1992; 31(1):63–66.

17. Rou M, Renfu X. The effect of Radix Astragali on mouse

marrow hemopoiesis. J Tradit Chin Med 1983; 3(3):199–204.

18. Na D, Liu FN, Miao ZF, et al. Astragalus extract inhibits

destruction of gastric cancer cells to mesothelial cells by antiapoptosis.

World J Gastroenterol 2009; 15(5):570–577.

19. Chu DT, Sun Y, Lin JR, et al. F3, a fractionated extract of

Astragalus membranaceus, potentiates lymphokine-activated

killer cell cytotoxicity generated by low dose recombinant

interleukin-2. Chin J Integr TradWest Med 1990; 10(1):34–36.

20. Chu DT, Lin JR,Wong WL. The in vitro potentiation of LAK

cell cytotoxicity in cancer and AIDS patients induced by F3, a

fractionated extract of Astragalus membranaceus. Chung Hua

Chung Liu Tsa Chih 1994; 16(3):167–171.

21. Wang Y, Qian XJ, Hadley HR, et al. Phytochemicals potentiate

interleukin-2 generated lymphokine-activated killer cell

cytotoxicity against murine renal cell carcinoma. Mol Biother

1992; 4(3):143–146.

22. Zhou S, Lu Z, Wang Y, et al. Study on the antineoplastic

activity of astragalus polysaccharide. Yao Wu Sheng Wu Ji

Shu 1995; 2(2):22–25.

23. Zhao KW, Kong HY. Effect of astragalan on secretion of tumor

necrosis factors in human peripheral blood mononuclear

cells. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1993;

13(5):263–265.

24. Shao BM, Xu W, Dai H, et al. A study on the immune receptors

for polysaccharides from the roots of Astragalus membranaceus,

a Chinese medicinal herb. Biochem Biophys Res

Commun 2004; 320;1103–1111.

25. Lei C, Yue H, Chen Y, et al. Effects of astragalus saponins

on ischemic scope, epicardial ECG, myocardial enzymes in

acute myocardial infarcted dog heart. Baiqiuen Yike Daxue

Xuebao 1995; 21(2):111–113.

26. Hikino H, Funayama S, Endo K. Hypotensive principle of

astragalus and hedysarum roots. Planta Med 1976; 30:297–

302.

27. Zhong G, Jiang Y, Wei Y, et al. Positive inotropic action of

Astragalus membranaceus saponins on isolated working heart.

Baiqiuen Yike Daxue Xuebao 1994; 20(5):448–449.

28. Wang Q, Li Y, Qi H, et al. Inotropic action of Astragalus

membranaceus Bunge saponins and its possible mechanism.

Zhongguo Zhongyao Zazhi 1993; 17(9):557–559.

29. Sun C, Zhong G, Zhan S, et al. Study on antioxidant effect

of astragalus polysaccharide. Zhongguo Yaolixue Tongbao

1996; 12(2):161–163.

30. Guo Q, Peng T, Yang Y, et al. Effect of drugs on Ca2+ influx

andCVB3-RNAreplication in cultured rat heart cells infected

with CVB3. Virol Sin 1996; 11(1):40–44.

31. Zhang WJ, Wojta J, Binder BR. Regulation of the fibrinolytic

potential of cultured human umbilical vein endothelial

cells: astragaloside IV down regulates plasminogen

activator inhibitor-1 and up regulates tissue-type

plasminogen activator expression. JVasc Res 1997; 34(4):273–

280.

32. Zhang WD, Chen H, Zhang C, et al. Astragaloside IV from

Astragalus membranaceus shows cardioprotection during myocardial

ischemia in vivo and in vitro. Planta Med 2006;

72:4–8.

33. QuYZ, Li M, Zhao YL, et al. Astragaloside IV attenuates cerebral

ischemia-reperfusion-induced increase in permeability

of the blood brain barrier in rats. Eur J Pharmacol 2009;

606:137–141.

34. Chang HM, But P. Pharmacology and Applications of

Chinese Materia Medica. Singapore: World Scientific,

1987.

35. Wu L, Liu H, Xue P, et al. Influence of a triplex superimposed

treatment on HBV replication and mutation during treating

chronic hepatitis B. Zhonghua Shi Yan He Lin Chuang Bing

Du Xue Za Zhi 2001; 15(3):236–238.

36. Zhao XZ. Effects of Astragalus membranaceus and Tripterygium

hypoglaucum on natural killer cell activity of peripheral

blood mononuclear in systemic lupus erythematosus.

Zhongguo Zhong Xi Yi Jie He Za Zhi 1992; 12(11):645, 669–

671.

37. Pan HF, Fang XH, Li WX, et al. Radix Astragali: A promising

new treatment option for systemic lupus erythematosus.

Med Hypothesis 2008; 71(2)311–312.

38. Xu A, Wang HB, Hoo RLC, et al. Selective elevation of

adiponectin production by the natural compounds derived

from a medicinal herb alleviates insulin resistance and

glucose intolerance in obese mice. Endocrinology 2009;

150(2):625–633.

39. Zuo C, Xie XS, Qiu HY, et al. Astragalus mongholicus ameliorates

renal fibrosis by modulating HGF and TGF in rats with

unilateral ureteral obstruction. J Zhejiang Univ Sci B 2009;

10(5):380–390.

40. Lee SJ, Oh SG, Seo SW, et al. Oral administration of Astragalus

membranaceus inhibits the development of DNFBinduced

dermatitis in NC/Nga mice. Biol Pharm Bull 2007;

30(8):1468–1471.

41. Vickers A, Goyal N, Harland R, et al. Do certain countries

produce only positive results? A systematic review of controlled

trials. Controlled Clin Trials 1998; 19:159–166.

42. Kemper KJ, Hood KL. Does pharmaceutical advertising affect

journal publication about dietary supplements? BMC

Complement Altern Med 2008; 8(11):1–8.

43. Duan P, Wang ZM. Clinical study on effect of astragalus in

efficacy enhancing and toxicity reducing of chemotherapy in

patients of malignant tumors. Zhongguo Zhong Xi Yi Jie He

Za Zhi 2002; 22(7):515–517.

36 Upton

44. Morazzoni P, Bombardelli P. Astragalus membranaceus (Fisch)

Bunge; Scientific Documentation 30. Milan, Italy: Indena

SpA, 1994;1–18.

45. Li SQ, Yuan RX, Gao H. Clinical observation on the treatment

of ischemic heart disease with Astragalus membranaceus. Kuo

Chung Hsi I Chieh Ho Tsa Chih 1995; 15(2):77–80.

46. Chen LX, Liao JZ, Guo WQ. Astragalus membranaceus on left

ventricular function and oxygen free radical in acute myocardial

infarction patients and mechanism of its cardiotonic

action. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1995;

15(3):141–143.

47. Lei ZY, Qin H, Liao JZ. Action of Astragalus membranaceus

on left ventricular function of angina pectoris. Chung Kuo

Chung Hsi I Chieh Ho Tsa Chih 1994; 14(4):199–202.

48. Shi HM, Dai RH, Wang SY. Primary research on the clinical

significance of ventricular late potentials (VLPs), and the impact

of mexiletine, lidocaine, and Astragalus membranaceus

on VLPs. Chung Hsi I Chieh Ho Tsa Chih 1991; 11(5):

265–267.

49. Luo HM, Dai RH, Li Y. Nuclear cardiology study on effective

ingredients of Astragalus membranaceus in treating heart

failure. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1995;

15(12):707–709.

50. Hou Y, Zhang Z, Su S, et al. Interferon induction and lymphocyte

transformation stimulated by Astragalus membranaceus

in mouse spleen cell cultures. Zhonghua Weisheng Wuxue

Hemian Yixue Zazhi 1981; 1(2):137–139.

51. Qian ZW, Mao SJ, Cai XC, et al. Viral etiology of chronic

cervicitis and its therapeutic response to -recombinant interferon.

Chin Med J 1990; 103:647–651.

52. Radix Astragali (huangqi). Pharmacopoeia of the People’s

Republic of China. Vol 1. Beijing, China: Chemistry and Industry

Press, 1997:442.

53. Zuo L, Dong X, Sun X. The curative effects of Astragalus

membranaceus Bunge (A-6) in combination with acyclovir on

mice infected with HSV-1. Virol Sin 1995; 10(2):177–179.

54. Wagner H, Bauer R, Peigen X, et al. Radix Astragali [Huang

Qi]. Chin Drug Monogr Anal 1997; 1(8):18.