Abstract
The effect of deoxypodophyllotoxin (DPT) isolated from Anthriscus sylvestris Hoffm. was evaluated in an in vivo animal model for antiasthmatic activity. DPT (1.0 to 5 mg/kg) was given orally to
ovalbumin (OVA)/alum-induced asthmatic mice. DPT reduced the number of infiltrated
eosinophils in bronchoalveolar lavage (BAL) fluid in a dose-dependent manner. Dexamethasone
(5 mg/kg), which was used as a positive control, also strongly inhibited the number
of infiltrated eosinophils. The effect of DPT on a transcript profile in a murine
asthma model was determined by RT-PCR, which showed that DPT decreased the mRNA levels
of the Th2 cytokines. Northern blot analysis showed that DPT also reduced both the
eotaxin and arginase I mRNA levels in a dose-dependent manner.
Key words
Deoxypodophyllotoxin (DPT) - eosinophils - bronchoalveolar lavage (BAL) - asthma -
Th2 cytokines
References
- 1
Holgate S T.
The epidemic of allergy and asthma.
Nature.
1999;
402
B2-4
- 2
Umetsu D T, McIntire J J, Akbari O, Macaubas C, DeKruyff R H.
Asthma: an epidemic of dysregulated immunity.
Nat Immunol.
2002;
3
715-20
- 3
Renauld J C.
New insights into the role of cytokines in asthma.
J Clin Pathol.
2001;
54
577-89
- 4
Ikeda R, Nagao T, Okabe H, Nakano Y, Matsunaga H, Katano M. et al .
Antiproliferative constituents in Umbelliferae plants. III. Constituents in the root
and the ground part of Anthriscus sylvestris Hoffm.
Chem Pharm Bull (Tokyo).
1998;
46
871-4
- 5
Masuda T, Oyama Y, Yonemori S, Takeda Y, Yamazaki Y, Mizuguchi S. et al .
Flow cytometric estimation on cytotoxic activity of leaf extracts from seashore plants
in subtropical Japan: isolation, quantification and cytotoxic action of (-)-deoxypodophyllotoxin.
Phytother Res.
2002;
16
353-8
- 6
Kim Y, Kim S B, You Y J, Ahn B Z.
Deoxypodophyllotoxin; the cytotoxic and antiangiogenic component from Pulsatilla koreana
.
Planta Med.
2002;
68
271-4
- 7
Sudo K, Konno K, Shigeta S, Yokota T.
Inhibitory effects of podophyllotoxin derivatives on Herpes simplex virus replication.
Antivir Chem Chemother.
1998;
9
263-7
- 8
Lin C X, Son M J, Ju H K, Moon T C, Lee E, Kim S H. et al .
Deoxypodophyllotoxin, a naturally occurring lignan, inhibits the passive cutaneous
anaphylaxis reaction.
Planta Med.
2004;
70
474-6
- 9
Boguchi D E, Charlton S L.
An asymmetric synthesis of (-)-deoxypodophyllotoxin.
J Org Chem.
1995;
60
588-93
- 10
Hasegawa S, Hirose Y.
A diterpene glycoside and lignans from seed of Thujopsis dolabrata
.
Phytochemistry.
1980;
19
2479-81
- 11
Sato T, Saito R, Jinushi T, Tsuji T, Matsuzaki J, Koda T. et al .
IFN-gamma-induced SOCS-1 regulates STAT6-dependent eotaxin production triggered by
IL-4 and TNF-alpha.
Biochem Biophys Res Commun.
2004;
314
468-75
- 12
Morrison A C, Correll P H.
Activation of the stem cell-derived tyrosine kinase/RON receptor tyrosine kinase by
macrophage-stimulating protein results in the induction of arginase activity in murine
peritoneal macrophages.
J Immunol.
2002;
168
853-60
- 13
Que L G, Kantrow S P, Jenkinson C P, Piantadosi C A, Huang Y C.
Induction of arginase isoforms in the lung during hyperoxia.
Am J Physiol.
1998;
275
L96-102
- 14
Munder M, Eichmann K, Moran J M, Centeno F, Soler G, Modolell M.
Th1/Th2-regulated expression of arginase isoforms in murine macrophages and dendritic
cells.
J Immunol.
1999;
163
3771-7
- 15
Wei L H, Jacobs A T, Morris Jr S M, Ignarro L J.
IL-4 and IL-13 upregulate arginase I expression by cAMP and JAK/STAT6 pathways in
vascular smooth muscle cells.
Am J Physiol Cell Physiol.
2000;
279
C248-56
- 16
Leung D Y, Bloom J W.
Update on glucocorticoid action and resistance.
J Allergy Clin Immunol.
2003;
111
3-22
- 17
Tinkelman D G, Reed C E, Nelson H S, Offord K P.
Aerosol beclomethasone dipropionate compared with theophylline as primary treatment
of chronic, mild to moderately severe asthma in children.
Pediatrics.
1993;
92
64-77
- 18
Lee S H, Son M J, Ju H K, Lin C X, Moon T C, Choi H G. et al .
Dual inhibition of cyclooxygenases-2 and 5-lipoxygenase by deoxypodophyllotoxin in
mouse bone marrow-derived mast cells.
Biol Pharm Bull.
2004;
27
786-8
- 19
Wills-Karp M.
Immunologic basis of antigen-induced airway hyperresponsiveness.
Annu Rev Immunol.
1999;
17
255-81
- 20
Romagnani S.
The role of lymphocytes in allergic disease.
J Allergy Clin Immunol.
2000;
105
399-408
- 21
Bousquet J, Chanez P, Lacoste J Y, Barneon G, Ghavanian N, Enander I. et al .
Eosinophilic inflammation in asthma.
N Engl J Med.
1990;
323
1033-9
- 22
Nagai T, Arai Y, Emori M, Nunome S Y, Yabe T, Takeda T. et al .
Anti-allergic activity of a Kampo (Japanese herbal) medicine ”Sho-seiryu-to (Xiao-Qing-Long-Tang)”
on airway inflammation in a mouse model.
Int Immunopharmacol.
2004;
4
1353-65
- 23
Mishra A, Weaver T E, Beck D C, Rothenberg M E.
Interleukin-5-mediated allergic airway inflammation inhibits the human surfactant
protein C promoter in transgenic mice.
J Biol Chem.
2001;
276
8453-9
- 24
Collins P D, Marleau S, Griffiths-Johnson D A, Jose P J, Williams T J.
Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation
in vivo
.
J Exp Med.
1995;
182
1169-74
- 25
Mould A W, Ramsay A J, Matthaei K I, Young I G, Rothenberg M E, Foster P S.
The effect of IL-5 and eotaxin expression in the lung on eosinophil trafficking and
degranulation and the induction of bronchial hyperreactivity.
J Immunol.
2000;
164
2142-50
- 26
Drazen J M, Arm J P, Austen K F.
Sorting out the cytokines of asthma.
J Exp Med.
1996;
183
1-5
- 27
Ray A, Cohn L.
Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation.
J Clin Invest.
1999;
104
985-93
- 28
Morris Jr S M.
Regulation of enzymes of the urea cycle and arginine metabolism.
Annu Rev Nutr.
2002;
22
87-105
- 29
Elias J A, Zhu Z, Chupp G, Homer R J.
Airway remodeling in asthma.
J Clin Invest.
1999;
104
1001-6
- 30
Louis C A, Mody V, Henry Jr W L, Reichner J S, Albina J E.
Regulation of arginase isoforms I and II by IL-4 in cultured murine peritoneal macrophages.
Am J Physiol.
1999;
276
R237-42
- 31
Wills-Karp M.
IL-12/IL-13 axis in allergic asthma.
J Allergy Clin Immunol.
2001;
107
9-18
- 32
Zimmermann N, King N E, Laporte J, Yang M, Mishra A, Pope S M. et al .
Dissection of experimental asthma with DNA microarray analysis identifies arginase
in asthma pathogenesis.
J Clin Invest.
2003;
111
1863-74
- 33
Lim Y H, Leem M J, Shin D H, Chang H B, Hong S W, Moon E Y. et al .
Cytotoxic constituents from the roots of Anthriscus sylvestris
.
Arch Pharm Res.
1999;
22
208-12
Prof. Hyeun Wook Chang
College of Pharmacy
Yeungnam University
Gyongsan 712-749
Korea
Phone: +82-53-810-2811
Fax: +82-53-810-4654
Email: hwchang@yumail.ac.kr