Online Submissions: http://www.journaltcm.
com J Tradit Chin Med 2013 June 15; 33(3): 413-416
info@journaltcm.com
Pharmacological effects of Astragaloside IV: a literature review
Shuang Ren, Hua Zhang, Yongping Mu, Mingyu Sun, Ping Liu
aa
Shuang Ren, Hua Zhang, Yongping Mu, Mingyu Sun, Key
Laboratory of Liver and Kidney Diseases, Institute of Liver
Diseases, Shuguang Hospital, Shanghai University of Tradi-
tional Chinese Medicine, Shanghai 201203, China
Ping Liu, E-institute of TCM Internal Medicine, Shanghai Mu-
nicipal Education Commission, Shanghai University of TCM,
Shanghai 201203, China
Correspondence to: Prof. Ping Liu, E-institute of TCM Inter-
nal Medicine, Shanghai Municipal Education Commission,
Shanghai University of TCM, Shanghai 201203, China. liuliv-
er@vip.sina.com
Telephone: +86-21-66001381
Accepted: March 6, 2013
Abstract
OBJECTIVE: To review the pharmacological effects
and mechanisms of action of Astragaloside IV in
Huangqi (Radix Astragali Mongolici).
METHODS: Aticles focusing on Astragaloside IV in
English and Chinese in databases were collected
and reviewed in order to summarize the latest ex-
traction separation, pharmacokinetics, and the
pharmacological effects of astrageloside IV.
RESULTS: Protective effects of Astrageloside IV on
the cardiovascular system, immune, digestive, ner-
vous system were identified, and the action mecha-
nisms were associated with regulation of the calci-
um balance, anti-oxydant, antiapoptosis, antivirus,
and so on.
CONCLUSION: Astrageloside IV has broad applica-
tion prospects, especially in cardiovascular diseas-
es, digestive diseases, cancer and other modern
high incidence, high-risk diseases, and could be de-
veloped as a medicine.
2013 JTCM. All rights reserved.
JTCM | www. journaltcm. com
ISSN 0255-2922
2013 JTCM. All rights reserved.
REVIEW
TOPIC
Key words: Astragaloside IV; Extraction; Pharmaco-
kinetics; Pharmacology
INTRODUCTION
In the Chinese Pharmacopoeia, Huangqi (Radix Astrag-
ali Mongolici) is described as the dried root of legumi-
nous plants Mongolia Astragalus [Astragalus membrana-
ceus (Fisch.) Bge.].1 It was first described in the Chinese
book Shen Nong Ben Cao Jing in 200 AD with a wide
range of treatment effects and no toxicity.2 It nourishes
Qi and blood, and is used for the treatment of cardio-
vascular disorders, hepatitis, kidney disease, and skin
diseases.
According to some reports, the constituents of
Huangqi (Radix Astragali Mongolici) include saponins,
polysaccharides and flavonoids. More than 40 constitu-
ents in Astragalus saponins have been identified from
the astragalus root, of which Astragaloside IV is the
main compound. Astragaloside IV has various pharma-
cological activities and is used as a quality-control
marker component of Huangqi (Radix Astragali Mon-
golici) in the Chinese Pharmacopoeia (2005 version).
In recent decades, the molecular analyses, pharmacoki-
netics and pharmacological actions of Astragaloside IV
have been studied extensively, which could enable its
clinical use.
STRUCTURE, EXTRACTION AND
PHARMACOKINETICS OF
ASTRAGALOSIDE IV
Astragalus saponin IV (also known as Astragaloside IV
and As IV) is 3-O-beta-D-xylopyranosyl-6-O-be-
ta-D-glucopyranosyl-cycloastragenol, is a lanolin alco-
hol-shaped tetracyclic triterpenoid saponin with high
polarity, and its molecular formula is C14H68O14. Its mo-
lecular structure is shown in Figure 1.
Some extraction and separation methods of Astragalo-
side IV (e.g., ultrafiltration, high-speed centrifugation,
413 June15, 2013 | Volume 33 | Issue 3 |
 Ren S et al. / Review
OH
O
OH
O functions of blood vessels in newborns
O
OH
CH2OH O
OH O change but also important endocrine glands that pro-
OH OH
OH
OH
Figure 1 Structural formula of Astragaloside IV
reflux, ultrasonic extraction, water extraction, alcohol
precipitation) can overcome the shortcomings of the
thermostability and water-insolubility of Astragaloside
IV. Such methods have less loss, shorter production cy-
cles, high yield and stability suitable for large-scale pro-
duction. Its rate of intravenous combination with plas-
ma protein A is 90%. Oral absorption (by passive dif-
fusion in the intestinal tract3) has low bioavailability
(7.4% 4) which is related to its high molecular weight,
low solubility in fat, and low transmittance in the
small intestine.5 Hence, the selection of pharmaceutical
forms is particularly important to improve the oral bio-
availability of Astrageloside IV.
PHARMACOLOGICAL ACTIVITIES OF
ASTRAGALOSIDE IV
Effect of astragaloside IV on cardiac function
Lack of a blood supply or oxygen in the myocardium
can weaken cardiac function and jeopardize health. Hu
et al 6 reported that Astragaloside IV can protect the
myocardial cells of rats from damage caused by lack of
oxygen, and increase the content and activity of super-
oxide dismutase (SOD) in the cytoplasm. Astragaloside
IV can improve the cardiac function of the ischemic
myocardium and myocardial infarction in rats.7 The
mechanism of action would be related to the calcium
antagonistic effects of Astragaloside IV. That is, As-
tragaloside IV inhibits the calcium overload caused by
ischemia and hypoxia, thereby restoring the balance be-
tween free calcium and total calcium, improving the ac-
tivity of calcium pumps in erythrocyte membranes,
and reducing the secondary injury caused by calcium.7
Coxsackie virus B (CVB3) is the main pathogenic fac-
tor of viral myocarditis. It has been shown that, after
the modeling of viral myocarditis by peritoneal injec-
tion to Balb/C mice with CVB3, intragastric adminis-
tration with 9% Astragaloside IV for 7 days can in-
crease the prevalence of survival of mice suffering from
myocarditis, inhibit the replication of CVB3, as well as
reduce collagen synthesis and apoptosis of myocardial
JTCM | www. journaltcm. com
cells.8,9 Li et al 10 confirmed that Astragaloside IV can
suppress myocardial oxidative injury as well as the
apoptosis of myocardial cells induced by adriamycin.
These findings showed that the mechanisms of action
of Astragaloside IV against myocardial damage may be
related to regulation of calcium homeostasis, anti-apop-
tosis and anti-oxidation.
Effect of Astragaloside IV on the endothelium and
Vascular endothelial cells are not only the place where
blood and tissue fluid complete metabolism and gas ex-
duce and secrete biologically active substances. Vascu-
lar endothelial cells play important parts in the mainte-
nance of vascular tension, regulation of blood pressure
and anti-thrombosis, and have important effects in the
pathogenesis of hypertension, cardiovascular disease
and cerebrovascular disease in vitro experiments dem-
onstrated that Astragaloside IV can promote the prolif-
eration of human umbilical vein endothelial cells and
the formation of tube-like structures. Astragaloside IV
can also promote angiogenesis and keep blood vessels
from reducing in vivo in zebrafish. The promotion of
angiogenesis can be closely associated with increases in
the expression of vascular endothelial cell growth factor
and its receptor, thereby activating the pathway of pro-
tein kinase B and phosphoinositide 3-kinase as well as
regulation of the expression of hypoxia inducible factor
protein.11,12 With regard to protection of endothelial
function, Ji13 showed that Astragaloside IV can resist li-
poprotein- or acute hyperglycemia-induced injury to
endothelial cells, increase the content of malondialde-
hyde (MDA) and SOD, and inhibit the decrease in en-
dothelial resistance and increase in the permeability of
single-layer endothelial cells. The mechanism of action
may be associated with regulation of the translocation
and activation of high glucose-induced protein kinase
C (PKC) and PKC2 in endothelial cells, downregu-
lation of expression of PKC protein and improving the
cytoskeleton of endothelial cells, especially those relat-
ed to F-actin reconfiguration.14 The pathogenesis of the
effect of Astragaloside IV on vascular endothelia needs
to be clarified, but it protects the endothelium, has an-
tioxidation effects, and promotes the growth of blood
vessels. Hence, it could cure diseases caused by abnor-
mal vascular function.
Effect of Astragaloside IV on metabolism of collagen
With respect to regulation of the decomposition and
synthesis of collagen, Astragaloside IV has a dual effect.
Astragaloside IV has protective effects on ultraviolet
A-induced photoaging in human fibroblasts, promotes
the proliferation of human fibroblasts, and prevents
collagen degradation (which is related to reducing ma-
trix metallopeptidase-1 expression and increasing ex-
pression of tissue inhibitor of metalloproteinases expres-
sion).15,16 Conversely, in vivo and in vitro experiments
414 June 15, 2013 | Volume 33 | Issue 3 |
 Ren S et al. / Review
have shown that Astragaloside IV can resist collagen de-
position, and treat the development of organic fibrosis
such as in the heart, liver, lungs, and kidneys. For ex-
ample, Meng et al 17 reported that Astragaloside IV syn-
ergizes with ferulic acid and can inhibit renal tubuloint-
erstitial fibrosis in rats and can also inhibit expression
of alpha smooth muscle actin and transforming growth
factor (TGF)-1 in NRK-49F and HK-2 cells in vitro.
Porcine serum-induced hepatic fibrosis in rats and
CVB3-induced cardiac-muscle fibrosis in mice can be
inhibited by Astragaloside IV,18-20 and is manifested as
downregulation of TGF-1 expression, and time-de-
pendent increases in MMP13/14 expression with dose.
Protective effect of Astragaloside IV on the liver
Cheng et al 21 noted that pretreatment with Astragalo-
side IV can protect against ischemia-reperfusion injury
after liver transplantation in rats, and participate in up-
regulation of the expression of the glucocorticoid recep-
tor and inhibition of nuclear factor-kappa B transcrip-
tional activity. Astragaloside IV acted on HepG2 cells
transfected with hepatitis-B virus, and secretion of hep-
atitis-B surface antigen, hepatitis-Be antigen as well as
serum HBV DNA levels were reduced.22 These results
pointed to the anti-inflammatory and antiviral activi-
ties of Astragaloside IV.
Effect of Astragaloside IV on the endocrine system
The metabolic syndrome is the main risk factor for car-
diovascular diseases and glycuresis. Wang et al 23 found
that treatment with Astragaloside IV could improve
fructopyranose-induced metabolic syndrome in rats by
increasing levels of nitric metabolite and cyclic guano-
sine monophosphate, which manifested as reduction
in blood pressure and improvement in insulin resis-
tance. In the treatment of mice with type-2 diabetes
with Astragaloside IV, the level of glycogen phospha-
tases and glucose-6-phosphatases in the liver was re-
duced, leading to relief of insulin resistance and re-
ductions in the level of blood sugar and triglycerides.24
Effect of Astragaloside IV on nervous system
The protective effects of Astragaloside IV against isch-
emic-reperfusion injury in the brain has been identi-
fied in a murine model of transient focal ischemia relat-
ed to antioxidation, and it is hoped that Astragaloside
IV can become a medicine to cure apoplexy.25-27 Astraga-
loside IV can relieve the decrease in the levels of dopa-
mines in 6-Hydroxydopamine-induced substantia neu-
rons,28 so it could be used for curing Parkinson's dis-
ease. Cheng et al 28 found that different concentrations
of total Astragalus saponins had dual effects on reviv-
ing the peripheral nervous system.
Effect of Astragaloside IV on the hematopoietic
system
Astragaloside IV can protect the hematopoietic system
from injury due to -rays in rats.30 It can prolong sur-
vival, increase three series of blood cells, promote the
JTCM | www. journaltcm. com
proliferation of bone-marrow stem cells, and reduce
the ratio of G0/G1 cells.30 It can also increase the ex-
pression of stem cell growth factor.31
Effect of Astragaloside IV on the organic immune
system
As a immune-enhancement agent, Astragaloside IV
could be used for curing cancer, and it does not have
obvious side effects.32 Whether used alone or with -el-
emene, Astragaloside IV can enhance the expression of
major histocompatibility complex molecules and im-
mune co-stimulus factors on the surface of dendritic
cells (DCs) as well as improve the secretion of interleu-
kin 2 and interleukin 6 to develop antigen presentation
and induce T-cell responses.33 These actions provide the
immunological basis for curing gastrointestinal cancers
in Traditional Chinese Medicine by tonifying Qi and
activating the blood circulation. In a murine model of
asthma, Astragaloside IV was shown to increase the lev-
el of interferon-r, improve hypersensitivity in the air-
ways, and decrease the expression of TGF-1 and thy-
mic stromal lymphopoietin at the protein level.34,35
Astragaloside IV against the proliferation of HepG2
cells was associated with a reduction in the expression
of oncogenes such as Vav 3.1, and was dose- and
time-dependent.36 It can also reverse multidrug resis-
tance in HepG2/glucosylceramide synthase (GCS)
cells, which may be related to reducing expression of
the GCS gene in cells.37 Furthermore, it had effects on
resistance of the proliferation of the human breast carci-
noma cell line MDA-MB-231 by reducing Akt phos-
phorylation.38
CONCLUSION
In the last decade, several studies have focused on the
extraction separation, pharmacokinetic and pharmaco-
logical activities of Astragaloside IV, but further investi-
gation is needed. For example, Astragaloside IV is con-
sidered to be a marker component of total Astragalo-
sides, what have different effects to Astragaloside IV.
Many researchers focused on the single pharmacologi-
cal action of Astragaloside IV; whether a combination
of Astragaloside IV with other medicines can be used
to cure diseases merits further study. Astragaloside IV
has a wide range of pharmacological actions reported
from several studies, so the prospect of clinical applica-
tion is quite good.
REFERENCES
1 State Pharmacopoeia Commission. Pharmacopoeia of the
People's Republic of China. 2005 edition. Beijing: Chemi-
cal Industry Press, 2005: 212-212.
2 Sun XY, Sun FY. Shen Nong Ben Cao Jing. Taiyuan: Shanxi
Science and Technology Press, 2010: 112-113.
3 Huang HP, Liu CX, Li YL, et al. Study on absorption ki-
netics of Astragaloside IV in rats intestines. Zhong Guo
Zhong Yao Za Zhi 2008; 33(13): 1609-1611.
415 June 15, 2013 | Volume 33 | Issue 3 |
 Ren S et al. / Review
4 Zhang Q, Zhu LL, Chen GG, et al. Pharmacokinetics of
Astragaloside iv in beagle dogs. Eur J Drug Metab Pharma-
cokinet 2007; 32(2): 75-79.
5 Huang CR, Wang GJ, Wu XL, et al. Absorption enhance-
ment study of Astragaloside IV based on its transport
mechanism in Caco-2 cells. Eur J Drug Metab Pharmaco-
kinet 2006; 31(1): 5-10.
6 Hu JY, Han J, Chu ZG, et al. Astragaloside IV attenuates
hypoxia-induced cardiomyocyte damage in rats by upregu-
lating superoxide dismutase-1 levels. Clin Exp Pharmacol
Physiol 2009; 36(4): 351-357.
7 Li ZP, Cao Q. Effects of Astragaloside IV on myocardial
calcium transport and cardiac function in ischemic rats.
Acta Pharmacol Sin 2002; 23(10): 898-904.
8 Chen P, Xie Y, Shen E, et al. Astragaloside IV attenuates
myocardial fibrosis by inhibiting TGF-1 signaling in cox-
sackievirus B3-induced cardiomyopathy. Eur J Pharmacol
2011; 658(2-3): 168-174.
9 Zhang ZC. Effect of Astragaloside on fibrosis in viral myo-
cardial myocarditic mice. Chin J New drug Clin Rem
2003; 22(9): 515-519
10 Li L, Tao HY, Chen JB. Anti-apoptosis effect of Astragalo-
side on adriamycin induced rats cardiotoxicity. Chin J Inte-
gr Med 2006; 26(11): 1011-1014.
11 Zhang L, Liu Q, Lu L, et al. Astragaloside IV stimulates
angiogenesis and increases HIF-1 accumulation via PI3K/
Akt pathway. J Pharmacol Exp Ther 2011; 338(2):
485-491.
12 Zhang Y, Hu G, Li S, et al. Pro-angiogenic activity of As-
tragaloside IV in HUVECs in vitro and zebrafish in vivo.
Mol Med Report 2012; 5(3): 805-811.
13 Ji KT, Tang JF, Chai JD, et al. Effect of Astragaloside
against the oxidative damage on endothelial cells. Zhong
Guo Zhong Xi Yi Jie He Za Zhi 2011; 31(6): 807-810.
14 Li HB, Gei YK, Zhang L, et al. Astragaloside IV im-
proved barrier dysfunction induced by acute high glucose
in human umbiIical vein endothehal cells. Life Sci 2006;
79(12): 1186-1193.
15 Liu X, Min W. Protective effects of Astragaloside against
ultraviolet a-induced photoaging in human fibroblasts.
Zhong Xi Yi Jie He Xue Bao 2011; 9(3): 328-332.
16 Wang X. Effects of Astragaloside on growth activity and
apoptosis of fibroblasts from human skin with and with-
out wrinkle in vitro. Chin J Med Aesthetics Cosmetol
2006; 12(2): 94-97.
17 Meng LQ, Tang JW, Wang Y, et al. Astragaloside IV syner-
gizes with ferulic acid to inhibit renal tubulointerstitial fi-
brosis in rats with obstructive nephropathy. Br J Pharma-
col 2011; 162(8): 1805-1818.
18 Liu H, Wei W, Sun WY, et al. Protective effects of Astraga-
loside IV on porcine-serum-induced hepatic fibrosis in
rats and in vitro effects on hepatic stellate cells. J Ethno-
pharmacol 2009; 122(3): 502-508.
19 Zhang ZC, Li SJ, Yang YZ. Effect of Astragaloside on
myocardial fibrosis in chronic myocarditis. Zhong Guo
Zhong Xi Yi Jie He Za Zhi 2007; 27(8): 728-731.
20 Li ZP. Dosage and time effects of astragaloside IV on myo-
cardial collagen and function of ischemie rats. Chin J Clin
Rehabil 2005; 9(23): 207-209.
21 Cheng MX, Chen ZZ, Cai YL, et al. Astragaloside IV pro-
tects against ischemia reperfusion in a murine model of or-
thotopic liver transplantation. Transplant Proc 2011; 43
(5): 1456-1461.
22 Wang S, Li J, Huang H, et al. Anti-hepatitis B virus activi-
ties of Astragaloside IV isolated from radix Astragali. Biol
JTCM | www. journaltcm. com
Pharm Bull 2009; 32(1): 132-135.
23 Zhang N, Wang XH, Mao SL, et al. Astragaloside IV im-
proves metabolic syndrome and endothelium dysfunction
in fructose-fed rats. Molecules 2011; 16(5): 3896-3907.
24 Lv L, Wu SY, Wang GF, et al. Effect of Astragaloside IV
on hepatic glucose-regulating enzymes in diabetic mice in-
duced by a high-fat diet and streptozotocin. Phytother Res
2010; 24(2): 219-224.
25 Zhu ZH, Wan HT, Li JH. Chuanxiongzine-astragaloside
IV decreases IL-1 and Caspase-3 gene expressions in rat
brain damaged by cerebral ischemia/reperfusion: A study
of real-time quantitative PCR assay. Sheng Li Xue Bao
2011; 63(3): 272-280.
26 Luo Y, Hong Z. Astragaloside IV protects against isch-
emic brain injury in a murine model of transient focal isch-
emia. Neurosci Lett 2004; 363(3): 218-223.
27 Li M, Qu YZ, Zhao ZW, et al. Astragaloside IV protects
against focal cerebral ischemia/reperfusion injury correlat-
ing to suppression of neutrophils adhesion-related mole-
cules. Neurochem Int 2012; 60(5): 458-465.
28 Chan WS, Durairajan SS, Lu JH, et al. Neuroprotective
effects of Astragaloside IV in 6-hydroxydopamine-treated
primary nigral cell culture. Neurochem Int 2009; 55(6):
414-422.
29 Cheng CY, Yao CH, Liu BS, et al. The role of Astragalo-
side in regeneration of the periphend nervesystem. J
Biomed Mater Res A 2006; 76(3): 463-469.
30 Li YR, Cao W, Guo J, et al. Comparative investigations
on the protective effects of rhodioside, ciwujianoside-B
and Astragaloside IV on radiation injuries of the hemato-
poietic system in mice. Phytother Res 2011; 25(5): 644-
653.
31 Tan YF, Yin XC, Xiong YJ, et al. Stem cell factor secretion
by bone mesenchymal stem cells stimulated with Astragalo-
side IV. Zhong Guo Dang Dai Er Ke Za Zhi 2010; 12(4):
290-292.
32 Hong F, Xiao W, Ragupathi G, et al. The known immuno-
logically active components of Astragalus account for only
a small proportion of the immunological adjuvant activity
when combined with conjugate vaccines. Planta Med
2011; 77(8): 817-824.
33 Lin L, Shen H, Wang LX, et al. Effect of Astragaloside
and -elemene on the immune function of dendritic cells
in mice. Southeast University: Medical Sciences 2011; 30
(2): 294-297.
34 Yuan X, Sun S, Wang S, et al. Effects of Astragaloside IV
on IFN-gamma level and prolonged airway dysfunction in
a murine model of chronic asthma. Planta Med 2011; 77
(4): 328-333.
35 Du Q, Gu XY, Feng GZ, et al. Effects of Astragaloside IV
on the expressions of transforming growth factor-1 and
thymic stromal lymphopoietin in a murine model of asth-
ma. Zhong Hua Yi Xue Za Zhi 2011; 91(44): 3139-3142.
36 Qi H, Wei L, Han Y, et al. Proteomic characterization of
the cellular response to chemopreventive triterpenoid As-
tragaloside IV in human hepatocellular carcinoma cell line
HepG2. Int J Oncol 2010; 36(3): 725-735.
37 Tian YZ, Miao QW, Zhao HL, et al. Effect of Astragalo-
side IV on reversal of multidrug resistance in hepatoma
cell line HepG2/GCS. Drugs and clinical 2011; 7(11):
778-779.
38 Deng Y, Chen HF. Effects of Astragalus injection and its
ingredients on proliferation and Akt phosphorylation of
breast cancer cell lines. Zhong Xi Yi Jie He Xue Bao 2009;
7(12): 1174-1180.
416 June 15, 2013 | Volume 33 | Issue 3 |