Abstract
Astragaloside IV (AST) is the main active constituent of Radix Astragali, a Chinese
herb traditionally used to prevent asthma attack from chronic asthma patients. Its
efficacy and action mechanisms in asthma attack prevention remain nonetheless to be
further explored. In this study, chronic asthma was induced exposing ovalbumin (OVA)
sensitized mice to repeated OVA challenges twice every two weeks for 12 weeks. Mice
were treated with AST for 4 weeks just after the final challenge. In this murine model
of chronic asthma, the airway dysfunction and remodeling remained severe and was accompanied
with suppression of the IFN-gamma level in the bronchoalveolar lavage fluid (BALF)
even four weeks after the final challenge, indicating that the airway structural changes
continued to develop even after interruption of OVA challenges. However, after AST
treatment, the airway hyperresponsiveness was sharply relieved, accompanied by the
reduction of collagen deposition and mucus production, meanwhile the inflammatory
cells were decreased but the IFN-gamma level increased in BALF. In conclusion, AST
could prevent the development of chronic asthma, thus reducing asthma attacks. Our
results indicated that it should be used as a supplementary therapy on preventing
asthma attacks from chronic asthma patients.
Key words
astragaloside IV - asthma - ovalbumin - IFN‐gamma - chronic asthma
References
- 1
Goldstein R A, Paul W E, Metcalfe D D, Busse W W, Reece E R.
NIH conference. Asthma.
Ann Intern Med.
1994;
121
698-708
- 2
Masoli M, Fabian D, Holt S, Beasley R.
The global burden of asthma: executive summary of the GINA Dissemination Committee
report.
Allergy.
2004;
59
469-478
- 3
Pavord I, Woodcock A, Parker D, Rice L.
Salmeterol plus fluticasone propionate versus fluticasone propionate plus montelukast:
a randomised controlled trial investigating the effects on airway inflammation in
asthma.
Respir Res.
2007;
8
67
- 4
Pauwels R A, Pedersen S, Busse W W, Tan W C, Chen Y Z, Ohlsson S V, Ullman A, Lamm C J,
O'Byrne P M.
Early intervention with budesonide in mild persistent asthma: a randomised, double-blind
trial.
Lancet.
2003;
361
1071-1076
- 5
Guilbert T W, Morgan W J, Zeiger R S, Mauger D T, Boehmer S J, Szefler S J, Bacharier L B,
Lemanske jr. R F, Strunk R C, Allen D B, Bloomberg G R, Heldt G, Krawiec M, Larsen G,
Liu A H, Chinchilli V M, Sorkness C A, Taussig L M, Martinez F D.
Long-term inhaled corticosteroids in preschool children at high risk for asthma.
N Engl J Med.
2006;
354
1985-1997
- 6
Xu X L, Chen X J, Ji H, Li P, Bian Y Y, Yang D, Xu J D, Bian Z P, Zhang J N.
Astragaloside IV improved intracellular calcium handling in hypoxia-reoxygenated cardiomyocytes
via the sarcoplasmic reticulum Ca-ATPase.
Pharmacology.
2008;
81
325-332
- 7
Hu J Y, Han J, Chu Z G, Song H P, Zhang D X, Zhang Q, Huang Y S.
Astragaloside IV attenuates hypoxia-induced cardiomyocyte damage in rats by upregulating
superoxide dismutase-1 levels.
Clin Exp Pharmacol Physiol.
2009;
36
351-357
- 8
Xu X L, Ji H, Gu S Y, Shao Q, Huang Q J, Cheng Y P.
Modification of alterations in cardiac function and sarcoplasmic reticulum by astragaloside
IV in myocardial injury in vivo.
Eur J Pharmacol.
2007;
568
203-212
- 9
Luo Y, Qin Z, Hong Z, Zhang X, Ding D, Fu J H, Zhang W D, Chen J.
Astragaloside IV protects against ischemic brain injury in a murine model of transient
focal ischemia.
Neurosci Lett.
2004;
363
218-223
- 10
Qu Y Z, Li M, Zhao Y L, Zhao Z W, Wei X Y, Liu J P, Gao L, Gao G D.
Astragaloside IV attenuates cerebral ischemia-reperfusion-induced increase in permeability
of the blood-brain barrier in rats.
Eur J Pharmacol.
2009;
606
137-141
- 11
Li H B, Ge Y K, Zhang L, Zheng X X.
Astragaloside IV improved barrier dysfunction induced by acute high glucose in human
umbilical vein endothelial cells.
Life Sci.
2006;
79
1186-1193
- 12
Li Z P, Cao Q.
Effects of astragaloside IV on myocardial calcium transport and cardiac function in
ischemic rats.
Acta Pharmacol Sin.
2002;
23
898-904
- 13
Qiu L H, Xie X J, Zhang B Q.
Astragaloside IV improves homocysteine-induced acute phase endothelial dysfunction
via antioxidation.
Biol Pharm Bull.
2010;
33
641-646
- 14
Navarrete A, Arrieta J, Terrones L, Abou-Gazar H, Calis I.
Gastroprotective effect of astragaloside IV: role of prostaglandins, sulfhydryls and
nitric oxide.
J Pharm Pharmacol.
2005;
57
1059-1064
- 15
Zhang C, Wang X H, Zhong M F, Liu R H, Li H L, Zhang W D, Chen H.
Mechanisms underlying vasorelaxant action of astragaloside IV in isolated rat aortic
rings.
Clin Exp Pharmacol Physiol.
2007;
34
387-392
- 16
Zhang W D, Chen H, Zhang C, Liu R H, Li H L, Chen H Z.
Astragaloside IV from Astragalus membranaceus shows cardioprotection during myocardial ischemia in vivo and in vitro.
Planta Med.
2006;
72
4-8
- 17
Zhang W D, Zhang C, Wang X H, Gao P J, Zhu D L, Chen H, Liu R H, Li H L.
Astragaloside IV dilates aortic vessels from normal and spontaneously hypertensive
rats through endothelium-dependent and endothelium-independent ways.
Planta Med.
2006;
72
621-626
- 18
Zhao Z, Wang W, Wang F, Zhao K, Han Y, Xu W, Tang L.
Effects of astragaloside IV on heart failure in rats.
Chin Med.
2009;
4
6
- 19
Lv L, Wu S Y, Wang G F, Zhang J J, Pang J X, Liu Z Q, Xu W, Wu S G, Rao J J.
Effect of astragaloside IV on hepatic glucose-regulating enzymes in diabetic mice
induced by a high-fat diet and streptozotocin.
Phytother Res.
2009;
24
219-224
- 20
Yuan W, Zhang Y, Ge Y, Yan M, Kuang R, Zheng X.
Astragaloside IV inhibits proliferation and promotes apoptosis in rat vascular smooth
muscle cells under high glucose concentration in vitro.
Planta Med.
2008;
74
1259-1264
- 21
Liu H, Wei W, Sun W Y, Li X.
Protective effects of astragaloside IV on porcine-serum-induced hepatic fibrosis in
rats and in vitro effects on hepatic stellate cells.
J Ethnopharmacol.
2009;
122
502-508
- 22
Zhang W J, Hufnagl P, Binder B R, Wojta J.
Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF-kappaB
activation and adhesion molecule expression.
Thromb Haemost.
2003;
90
904-914
- 23
Wang Y P, Li X Y, Song C Q, Hu Z B.
Effect of astragaloside IV on T, B lymphocyte proliferation and peritoneal macrophage
function in mice.
Acta Pharmacol Sin.
2002;
23
263-266
- 24
Yu J, Zhang Y, Sun S, Shen J, Qiu J, Yin X, Yin H, Jiang S.
Inhibitory effects of astragaloside IV on diabetic peripheral neuropathy in rats.
Can J Physiol Pharmacol.
2006;
84
579-587
- 25
Zhang Y, Zhu H, Huang C, Cui X, Gao Y, Huang Y, Gong W, Zhao Y, Guo S.
Astragaloside IV exerts antiviral effects against coxsackievirus B3 by upregulating
interferon-gamma.
J Cardiovasc Pharmacol.
2006;
47
190-195
- 26
Leigh R, Ellis R, Wattie J, Southam D S, De Hoogh M, Gauldie J, O'Byrne P M, Inman M D.
Dysfunction and remodeling of the mouse airway persist after resolution of acute allergen-induced
airway inflammation.
Am J Respir Cell Mol Biol.
2002;
27
526-535
- 27
Webb D C, McKenzie A N, Koskinen A M, Yang M, Mattes J, Foster P S.
Integrated signals between IL-13, IL-4, and IL-5 regulate airways hyperreactivity.
J Immunol.
2000;
165
108-113
- 28
Leigh R, Ellis R, Wattie J N, Hirota J A, Matthaei K I, Foster P S, O'Byrne P M, Inman M D.
Type 2 cytokines in the pathogenesis of sustained airway dysfunction and airway remodeling
in mice.
Am J Respir Crit Care Med.
2004;
169
860-867
- 29
Du Q, Chen Z, Zhou L F, Zhang Q, Huang M, Yin K S.
Inhibitory effects of astragaloside IV on ovalbumin-induced chronic experimental asthma.
Can J Physiol Pharmacol.
2008;
86
449-457
- 30
Mathur M, Herrmann K, Li X, Qin Y, Weinstock J, Elliott D, Monahan J, Padrid P.
TRFK-5 reverses established airway eosinophilia but not established hyperresponsiveness
in a murine model of chronic asthma.
Am J Respir Crit Care Med.
1999;
159
580-587
- 31
Wang X, Xu W, Kong X, Chen D, Hellermann G, Ahlert T A, Giaimo J D, Cormier S A, Li X,
Lockey R F, Mohapatra S, Mohapatra S S.
Modulation of lung inflammation by vessel dilator in a mouse model of allergic asthma.
Respir Res.
2009;
10
66
- 32
Ellis R, Leigh R, Southam D, O'Byrne P M, Inman M D.
Morphometric analysis of mouse airways after chronic allergen challenge.
Lab Invest.
2003;
83
1285-1291
- 33
Page K, Lierl K M, Herman N, Wills-Karp M.
Differences in susceptibility to German cockroach frass and its associated proteases
in induced allergic inflammation in mice.
Respir Res.
2007;
8
91
- 34
Ngoc P L, Gold D R, Tzianabos A O, Weiss S T, Celedon J C.
Cytokines, allergy, and asthma.
Curr Opin Allergy Clin Immunol.
2005;
5
161-166
- 35
Truyen E, Coteur L, Dilissen E, Overbergh L, Dupont L J, Ceuppens J L, Bullens D M.
Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA measurement
in sputum of asthma patients.
Thorax.
2006;
61
202-208
- 36
Christ A P, Rodriguez D, Bortolatto J, Borducchi E, Keller A, Mucida D, Silva J S,
Leite L C, Russo M.
Enhancement of Th1 lung immunity induced by recombinant Mycobacterium bovis BCG attenuates
airway allergic disease.
Am J Respir Cell Mol Biol.
2010;
43
243-252
- 37
Chang H H, Chen C S, Lin J Y.
High dose vitamin C supplementation increases the Th1/Th2 cytokine secretion ratio,
but decreases eosinophilic infiltration in bronchoalveolar lavage fluid of ovalbumin-sensitized
and challenged mice.
J Agric Food Chem.
2009;
57
10471-10476
- 38
KuoLee R, Zhou H, Harris G, Zhao X, Qiu H, Patel G B, Chen W.
Inhibition of airway eosinophilia and pulmonary pathology in a mouse model of allergic
asthma by the live vaccine strain of Francisella tularensis.
Clin Exp Allergy.
2008;
38
1003-1015
- 39
Yang M, Kumar R K, Foster P S.
Interferon-gamma and pulmonary macrophages contribute to the mechanisms underlying
prolonged airway hyperresponsiveness.
Clin Exp Allergy.
2010;
40
163-173
- 40
Fujita H, Teng A, Nozawa R, Takamoto-Matsui Y, Katagiri-Matsumura H, Ikezawa Z, Ishii Y.
Production of both IL-27 and IFN-gamma after the treatment with a ligand for invariant
NK T cells is responsible for the suppression of Th2 response and allergic inflammation
in a mouse experimental asthma model.
J Immunol.
2009;
183
254-260
- 41
Herbert C, Hettiaratchi A, Webb D C, Thomas P S, Foster P S, Kumar R K.
Suppression of cytokine expression by roflumilast and dexamethasone in a model of
chronic asthma.
Clin Exp Allergy.
2008;
38
847-856
- 42
Brewster C E, Howarth P H, Djukanovic R, Wilson J, Holgate S T, Roche W R.
Myofibroblasts and subepithelial fibrosis in bronchial asthma.
Am J Respir Cell Mol Biol.
1990;
3
507-511
- 43
Rose M C, Nickola T J, Voynow J A.
Airway mucus obstruction: mucin glycoproteins, MUC gene regulation and goblet cell
hyperplasia.
Am J Respir Cell Mol Biol.
2001;
25
533-537
- 44
Cohn L, Homer R J, Niu N, Bottomly K.
T helper 1 cells and interferon gamma regulate allergic airway inflammation and mucus
production.
J Exp Med.
1999;
190
1309-1318
Prof. Shouchuan Wang
Department of Pediatrics
Nanjing University of Chinese Medicine
282#, Hanzhong Road
Nanjing
China
Telefon: +86 25 86 79 81 82
Fax: +86 25 86 79 81 82
eMail: wangscnj@gmail.com
