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研究生：	黃文忠 Wen-Chung Huang
論文名稱：	絞股藍抑制OVA致敏小鼠呼吸道發炎反應 Gynostemma pentaphyllum attenuates airways inflammation in OVA-sensitized asthmatic mice
指導教授：	李銘亮 Li, Ming-Liang 郭敏玲 Kuo, Ming-Ling
學位類別：	博士 Doctor
系所名稱：	生命科學系 Department of Life Science
論文出版年：	2008
畢業學年度：	96
語文別：	英文
論文頁數：	130
中文關鍵詞：	絞股藍、氣喘、輔助型T 細胞、呼吸道過度反應、細胞激素
英文關鍵詞：	Gynostemma pentaphyllum, asthma, T helper cells, airway hyperresponsiveness, cytokines
論文種類：	學術論文
相關次數：	點閱：305 下載：6
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氣喘是一種慢性氣管發炎反應的疾病，在發作時常有窒息致命的危險性。氣喘患者發病時的病徵會出現呼吸困難、喘嗚音、胸悶和咳嗽等症狀，甚至會出現呼吸道收縮狹窄，呼吸道黏液增加，導致呼吸道被黏液阻塞窒息死亡。慢性氣喘患者呼吸道會出現大量嗜酸性球浸潤的現象，以及呼吸道過度反應 (airways hyperresponsiveness，AHR)的情形；更多的研究發現，Th2細胞所分泌的IL-4、IL-5、IL-9以及IL-13等細胞激素主要影響氣喘的病理表現，如果可以抑制Th2的細胞活化以及相關的激素分泌，將有助於減低氣喘的症狀。雖然類固醇是一種普遍用來治療氣喘的藥物，但其除了具有抑制免疫功能與呼吸道發炎的療效之外，也會出現許多不當的副作用，所以東方與西方醫學界都希望可以尋找更多的方法來治療氣喘的疾病。絞股藍 (Gynostemma pentaphyllum，又名七葉膽)為葫蘆科絞股藍屬的植物，因為生長分佈區域，加上已經被鑑定出之90多種絞股藍皂甙 (gypenoside)中，有六種與人蔘的皂甙相同，故絞股藍又有南方人蔘之稱。並且近年來學者對於絞股藍的藥理與臨床研究發現，絞股藍在臨床上有極多的功效；包括降血脂、血糖、抗衰老、抗腫瘤、增強免疫力等的作用。
我們發現接受腹腔注射或口服絞股藍抽出物5天的小鼠，其脾臟細胞分泌較高的Th1相關的細胞激素與IgG2a，並且可抑制Th2 相關細胞激素的分泌。所以絞股藍可能具有調節與改變Th1及Th2細胞之間的細胞激素分泌平衡性的能力，或許可以抑制氣喘病人體內較強的Th2活性，應該具有減緩氣喘病情的療效。本論文以雞卵蛋白 (ovalbumin, OVA) 為過敏原，引起小鼠產生呼吸道發炎等氣喘病徵，來測試絞股藍是否具有減緩氣喘的發炎與抑制其Th2活性的反應。我們設計幾個實驗模式，在先以腹腔注射致敏並吸入OVA 3次的IH3 模式中，OVA致敏小鼠餵食7天絞股藍抽出物，發現這些小鼠呼吸道過度反應、嗜酸性球浸潤與血清的OVA-IgE有明顯下降的現象；若再吸入過敏原 2次，除了更明顯抑制發炎病徵之外，也可以顯著抑制OVA-刺激培養之脾臟細胞分泌 Th2細胞激素。此外，我們亦以3個長期給藥模式，來檢定絞股藍抽出物是否對氣喘小鼠具有預防 (T-A 模式)、長期預防加治療 (T-B 模式)、或是長期治療 (T-C 模式) 的效果。實驗結果顯示，於T-A 實驗模式中，絞股藍抽出物並無法顯著降低AHR、嗜酸性球浸潤、以及血清的OVA-IgE等的發炎病徵。但是在T-A模式口服絞股藍的小鼠，在接觸過敏原的階段持續口服絞股藍 (T-B 模式)，以及一開始接觸過敏原之後就長期給予絞股藍抽出物 (T-C 模式)，兩者都可以有效減緩氣喘小鼠的發炎病徵與抑制其Th2活性的反應。綜合所有OVA致敏小鼠的實驗模式試驗，我們認為絞股藍具有治療氣喘模式小鼠的呼吸道發炎反應與抑制過度免疫反應的效果，但卻無法有效預防氣喘的發生。

Asthma is characterized as a chronic disease which causes an important public health problem worldwide. The symptoms of asthma include wheezing, cough, shortness of breath, airway narrowing and mucus increase cause suffocation and death. In addition, more eosinophils infiltration and airways hyperresponsiveness (AHR) are usually found in the airways of asthmatic patients. The Th2-type cytokines appear to be crucial in the pathogenesis of asthma. Thus, to suppress Th2-induced cytokines secretion might be able to inhibit asthma symptoms. Steroid is commonly used to treat asthma. Although it suppresses the respiratory track inflammation, long-term usage of steroids may cause potential side effects. Therefore, doctors in Western and Chinese medicine desire to have alternative ways to treat asthma. Gynostemma pentaphyllum is a perennial liana plant and widely used as an herbal tea in Japan, southern China and Taiwan. About 90 different gypenosides have been identified from the extract of G. pentaphyllum. Among them, six gypenosides are the same with the ginsenosides from Panax ginseng. Recent studies found that G. pentaphyllum has additional pharmacological effects on the inhibition of blood-sugar, hyperlipidaemia, and the treatment of hepatitis.
Our results indicated that the extract of G. pentaphyllum could promote the expression of Th1 cytokines and IgG2a secretion from splenocytes of mice that were intraperitoneally injected or orally administrated with the extract for 5 consecutive days. Since more Th2-associated cytokines in lung were found in asthmatic patients, we proposed that G. pentaphyllum might be able to module the balance of Th1/Th2 cytokines and to suppress the inflammation in asthma airways. Chicken ovalbumin (OVA) was used as the allergen to induce asthmatic immune responses and symptoms. We tested the efficacy of G. pentaphyllum in 5 experimental models. BALB/c mice were firstly sensitized with intraperitoneal injection and challenged with 3 times of OVA inhalation (IH3 model) or 5 times (IH3 model). G. pentaphyllum was orally administrated for 7 consecutive days before the end of the OVA challenge. Asthmatic symptoms were examined, including AHR, eosinohpilia in lungs, and serum levels of OVA-specific IgG1 and IgE. The cytokine concentrations of the supernatants of OVA-activated splenocytes were also determined. Oral administration of G. pentaphyllum extracts significantly attenuated AHR and inhibited eosinophil infiltration in mice of both IH3 and IH5 models. Significantly decreased serum OVA-specific antibodies and Th2-type cytokines, as well as the increased IFN- production, were detected in the IH5 model. Moreover, whether the long-administration of G. pentaphyllum was able to prevent asthma was examined in T-A model. The mice received the extract for 28 days before the sensitization with OVA. No significant reduction of asthma symptoms was detected. In the other 2 models, mice received the G. pentaphyllum extract before and during the contact with OVA (the T-B model) and 28 days since the first dose of OVA injection (the T-C model). The result showed that G. pentaphyllum extract could significantly attenuate inflammatory responses and Th2-cell activity. Therefore, the results suggested that G. pentaphyllum inhibited airway inflammation and over-active immune responses, but can not prevent the symptoms in asthmatic mice.

Chapter 1: Literature Review                             1
    1-1 Background and epidemiology of asthma                        1
    1-2 Pathogenesis of asthma                                       3
    1-3 The role of Th cells in pathogenesis of asthma                     5
    1-4 Therapy of asthma                                            8
1-5 Introduction of Gynostemma pentaphyllum                       9
1-5-1 Effect on hyperlipidaemia                                  10
1-5-2 Effect on blood embolism                                  11
1-5-3 Effects on cardiovascular system                             11
1-5-4 Effect on hyperglycemia                                   11
1-5-5 Effect on cancer                                          12
    1-6 Background of Chinese herbal medicines to asthma                12
    1-7 Purpose of treat asthma by G. pentaphyllum                      15


Chapter 2 :Material and Methods                          17
    2-1 The experimental animal and commonly used experiment method    17
    2-1-1 Experimental animal                                       17
    2-1-2 Preparation of G. pentaphyllum extracts                        17
    2-1-3 Serum collection                                          18
    2-1-4 Splenocyte isolation                                       18
    2-1-5 ELISA assay for total immunoglobulins                        19
    2-1-5-1 IgG                                                   19
    2-1-5-2 IgG1 and IgG2a                                         20
    2-1-5-3 IgM                                                   20
    2-1-5-4 IgA                                                   20
    2-1-6 ELISA assay for cytokine concentration                        21
    2-1-7 Measurement of airway hyperresponsiveness (AHR)             22
    2-1-8 Bronchoalveolar lavage fluid (BALF) collection                 22
    2-1-9 Lung histology                                            22
    2-1-10 Statistics analysis                                         23
    2-2 Immune regulatory function of G. pentaphyllum                    23
    2-2-1 BALB/c mice were received intraperitoneal injection of
G. pentaphyllum                                           23
    2-2-2 Short-term oral administration of G. pentaphyllum extracts         24
    2-2-3 Spleen cell cultures                                        24
    2-2-4 Analysis of serum ALT and AST                              25
    2-2-5 Histological examination                                    25
    2-3 The effect of G. pentaphyllum on airway inflammation of
OVA-sensitized mice                                         26
    2-3-1 Experimental evaluation of whether G. pentaphyllum inhibited
airway inflammatory in the asthmatic mice of IH3 model           26
    2-3-1-1 Mice sensitization and drug treatment                        26
    2-3-2 Experimental evaluation of treating asthma with G. pentaphyllum inhibited airway inflammatory in the mice of IH5 model           27
    2-3-2-1 Mice sensitization and drug treatment                        27
    2-3-3 Evaluation of preventive effect of G. pentaphyllum extracts in
OVA-sensitized mice                                       28
    2-3-4 Experimental evaluation of preventive and therapeutic asthma
of G. pentaphyllum extracts in OVA-sensitized mice.              29
    2-3-5 Experimental evaluation of therapeutic asthmatic effect of
G. pentaphyllum extracts in OVA-sensitized mice.                30

Chapter 3: Results                                       31
    3-1 Immune regulatory test of G. pentaphyllum                       31
    3-1-1 G. pentaphyllum of intraperitoneally injected in BALB/c mice      31
    3-1-1-1 G. pentaphyllum induced higher levels of immunoglobulin in
mice serum                                            31
    3-1-1-2 G. pentaphyllum enhanced immunoglobulin production from
 spleen cells                                            32
    3-1-1-3 G. pentaphyllum enhanced production of cytokines from
activated spleen cells                                    33
3-1-2 Short-term oral administration of G. pentaphyllum extracts
 modulated immune responses                               34
3-1-2-1 Higher levels of immunoglobulin in mice serum induced
by oral treatment of G. pentaphyllum                        34
    3-1-2-2 G. pentaphyllum enhanced immunoglobulin production from LPS-activated spleen cells                               35
3-1-2-3 G. pentaphyllum changed the production of cytokines from ConA-activated spleen cells                              36
    3-1-2-4 Effect of G. pentaphyllum extract on blood biochemistry
and histopathology of internal organs                      37
3-2 The effect of G. pentaphyllum on airway inflammation of
OVA-sensitized and challenged mice                          38
    3-2-1 To evaluate oral administration of G. pentaphyllum extracts
treated OVA-sensitive mice in IH3 model                     38
    3-2-1-1 G. pentaphyllum attenuated OVA-induced airway
Inflammation                                         38
    3-2-1-2 G. pentaphyllum inhibited serum OVA-specific antibodies      39
    3-2-1-3 G. pentaphyllum reduced IL-5 production by spleen cells from OVA-sensitized mice                                   39
    3-2-2 To evaluate oral administration of G. pentaphyllum extracts
treated OVA-sensitive mice in IH5 model                     40
    3-2-2-1 G. pentaphyllum reduced further allergen-induced airway
inflammation                                         40
    3-2-2-2 G. pentaphyllum inhibited serum OVA-specific antibodies in
the mice of IH5 model                                  41
    3-2-2-3 G. pentaphyllum modulated cytokine secretion by spleen
cells and Th2-type cytokines in BALF from OVA-sensitized
mice                                                42
    3-2-2-4 Histopathologic examination                             43
3-2-3 No significant preventive effect of G. pentaphyllum extracts
was detected in OVA-sensitized mice                        43
    3-2-4 Long-term administration of G. pentaphyllum extracts in OVA-
sensitized mice                                         44
    3-2-4-1 Long-term administration of G. pentaphyllum reduced
allergen-induced airway inflammation                     44
    3-2-4-2 Long-term administration of G. pentaphyllum inhibited serum OVA-specific antibodies                                45
    3-2-4-3 Long-term administration of G. pentaphyllum modulated
cytokine secretion by spleen cells from OVA-sensitized mice    45
3-2-5 The therapeutic effect of long-term administration of G.
pentaphyllum extracts in OVA-sensitized mice               46
    3-2-5-1 Lower dose of oral administration, but not inhalation, of
G. pentaphyllum reduced OVA-induced airway inflammation   46
    3-2-5-2 Lower dose of oral administration of G. pentaphyllum reduced
serum OVA-specific antibodies in asthmatic mice            47
    3-2-5-3 Lower dose of oral administration of G. pentaphyllum
modulated cytokine secretion from spleen cells from
OVA-sensitized mice                                   47

Chapter 4: Discussions                                  49
    4-1 G. pentaphyllum effect on immune modulation                  49
    4-2 G. pentaphyllum effect on therapy of asthma                   53

Chapter 5: Conclusions                                  62
Chapter 6: References                                   63
Chapter 7: Figures and Tables                            79
                                

Akdis, C.A. 2006. Allergy and hypersensitivity mechanisms of allergic disease. Curr Opin Immunol 18: 718-726.
Alemany, R., Suzuki, K., and Curiel, D.T. 2000. Blood clearance rates of adenovirus type 5 in mice. J Gen Virol 81: 2605-2609.
Bachert, C., van Cauwenberge, P. 2007 Desloratadine treatment for intermittent and persistent allergic rhinitis: a review. Clin Ther 2007 29:1795-802.
Balachandran, A., Shivbalan, S., and Subramanyam, L. 2001 Drug therapy of childhood asthma. Indian J Pediatr 68 (Suppl 4): S12-16.
Barnes, P.J. 2006a. Corticosteroids: the drugs to beat. Eur J Pharmacol 533 2-14.
Barnes, P.J. 2006b. Drugs for asthma. Br J Pharmacol 147: Suppl 1: S297-303.
Barrios, R.J., Kheradmand, F., Batts, L., and Corry, D.B. 2006. Asthma: pathology and pathophysiology. Arch Pathol Lab Med 130: 447-451.
Bender, B., G, , Fuhlbrigge, A., Walders, N., and Zhang, L. 2007. Overweight, race, and psychological distress in children in the Childhood Asthma Management Program. Pediatrics 120: 805-813.
Bielory, L. 2004. Complementary and alternative interventions in asthma, allergy, and immunology. Ann Allergy Asthma Immunol 93: Suppl :S45-54.
Blank, U., Jouvin, M.H., Guérin-Marchand, C., and Kinet, J.P. 2003. The high-affinity IgE receptor: lessons from structural analysis. Med Sci 19: 63-69.
Boushey, H.A. 1982. Bronchial hyperreactivity to sulfur dioxide: physiologic and political implications. J Allergy Clin Immunol 69: 335-338.
Brusasco, V. and Crimi, E. 2001. Methacholine provocation test for diagnosis of allergic respiratory diseases. Allergy 56: 1114-1120.
Busse, W.W. and Lemanske, R.F. 2001. Advances in Immunology: Asthma. N Engl J Med 344: 350-362.
Chakir, J., Shannon, J., Molet, S., Fukakusa, M., and Elias, J.A. 2003. Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-alpha, IL-11, IL-17, and type I and type III collagen expression. J Allergy Clin Immunol 111: 1293-1298.
Chan, C.K., Kuo, M.L., Shen, J.J., See, L.C., Chang, H.H., and Huang, J.L. 2006. Ding Chuan Tang, a Chinese herb decoction, could improve airway hyper-responsiveness in stabilized asthmatic children: a randomized, double-blind clinical trial. Pediatr Allergy Immunol 17: 316-322.
Chiang, C.H., Tang, Y.C., Lin, M.W., and Chung, M.Y. 2007. Association between the IL-4 promoter polymorphisms and asthma or severity of hyperresponsiveness in Taiwanese. Respirology 12: 42-48.
Chu, E.K. and Drazen, J.M. 2005. Asthma: one hundred years of treatment and onward. Am J Respir Crit Care Med 171: 1202-1208.
Circosta, C., De, P.R., and Occhiuto, F. 2005. Cardiovascular effects of the aqueous extract of Gynostemma pentaphyllum Makino. Phytomedicine 12: 638-643.
Cohn, L., Elias, J.A., and Chupp, G.L. 2004. Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol 22: 789-815.
Cohn, L., Tepper, J.S., and Bottomly, K. 1998. IL-4-independent induction of airway hyperresponsiveness by Th2, but not Th1, cells. J Immunol 161: 3813-3816.
Cour, B., Molgaard, P., and Yi, Z. 1995. Traditional Chinese medicine in treatment of hyperlipidaemia. J Ethnopharmacol 46: 125-129.
Cui, J., Eneroth, P., and Bruhn, J.S. 1999. Gynostemma pentaphyllum: identification of major sapogenins and differentiation from Panax species. Eur J Pharm Sci 8: 187-191.
Cui, T., Wu, J., Pan, S., and Xie, J. 2003. Polymorphisms in the IL-4 and IL-4R [alpha] genes and allergic asthma. Clin Chem Lab Med 41: 888-892.
Fehérvari, Z. and Sakaguchi, S. 2004. Development and function of CD25+CD4+ regulatory T cells. Curr Opin Immunol 16: 203-208.
Finkelman, F.D., Yang, M., Perkins, C., Schleifer, K., Sproles, A., Santeliz, J., Bernstein, J.A., Rothenberg, M.E., Morris, S.C., and Marsha, W.-K. 2005. Suppressive effect of IL-4 on IL-13-induced genes in mouse lung. J Immunol 174: 4630-4638.
Finotto, S., Hausding, M., Doganci, A., Maxeiner, J.H., Lehr, H.A., and Luft, C. 2005. Asthmatic changes in mice lacking T-bet are mediated by IL-13. Int Immunol 17: 993-1007.
Fixman, E.D., Stewart, A., and Martin, J.G. 2007. Basic mechanisms of development of airway structural changes in asthma. Eur Respir J 29: 379-389.
Garrod, R. and Lasserson, T. 2007. Role of physiotherapy in the management of chronic lung diseases: An overview of systematic reviews. Respir Med 101: 2429-2436.
Georas, S.N., Guo, J., Fanis, U.D., and Casolaro, V. 2005. T-helper cell type-2 regulation in allergic disease. Eur Respir J 26: 1119-1137.
Gern, J.E. 2003. Mechanisms of virus-induced asthma. J Pediatr 142: Suppl:S9-13.
Glimcher, L.H. and Murphy, K.M. 2000. Lineage commitment in the immune system: The T helper lymphocyte grows up. Gene Dev 14: 1693-1711.
Gounni, A.S., Hamid, Q., Rahman, S.M., Hoeck, J., Yang, J., and Shan, L. 2004. IL-9-mediated induction of eotaxin1/CCL11 in human airway smooth muscle cells. J Immunol 173: 2771-2779.
Hamerman J.A., Ogasawara K., and Lanier L.L. 2005. NK cells in innate immunity. Curr Opin Immunol 17: 29-35.
Hesse, C., Razmovski-Naumovski, V., Duke, C.C., Davies, N.M., and Roufogalis, B.D. 2007. Phytopreventative effects of Gynostemma pentaphyllum against acute Indomethacin-induced gastrointestinal and renal toxicity in rats. Phytother Res 21: 523-530.
Ho, W.C., Hartley, W.R., Myers, L., Lin, M.H., Lin, Y.S., Lien, C.H., and Lin, R.S. 2007. Air pollution, weather, and associated risk factors related to asthma prevalence and attack rate. Environ Res 104: 402-409.
Holtzman, M.J. 2003. Drug development for asthma. Am J Respir Cell Mol Biol 29: 163 -171.
Homer, R.J. and Elias, J.A. 2000. Consequences of long-term inflammation: airway remodeling. Clin Chest Med 21: 331-343.
Horvath, G. and Wanner, A. 2006. Inhaled corticosteroids: effects on the airway vasculature in bronchial asthma. Eur Respir J 27: 172-187.
Hou, J., Liu, S., Ma, Z., Lang, X., Wang, J., and Liang, Z. 1991. Effects of Gynostemma pentaphyllum makino on the immunological function of cancer patients. J Tradit Chin Med 11: 47-52.
http://gaia.org.tw/air/asthma/q02.htm.
http://tw.news.yahoo.com/060401/39/2zu42.html.
Huang, W.C., Kuo, M.L., Li, M.L., Yang, Y.C., Liou, C.L., and Shen, J.J. 2007a. The extract of Gynostemma pentaphyllum enhanced the production of antibodies and cytokines in mice. Yakugaku Zasshi 127: 889-896.
Huang, W.C., Shen, J.J., Liou, C.L., Kuo, M.L., Chang, Y.P., Yang, Y.C., and Li, M.L. 2007b. Enhancing Th1 cell activities in mice by short-term oral administration of Gynostemma pentaphyllum extracts. BioFormosa 42: 9-16.
Huntley, A. and Ernst, E. 2000. Herbal medicines for asthma: a systematic review. Thorax 55: 925-929.
Jeong, H.G. 1999. Differential effects of B- and T-lymphocyte mitogens on cytochrome P450 in mice. Toxicol Let 104 57-64.
Jin, M.H., Yook, J., Lee, E., Lin, C.X., Quan, Z., Son, K.H., Bae, K.H., Kim, H.P., Kang, S.S., and Chang, H.W. 2006. Anti-inflammatory Activity of Ailanthus altissima in Ovalbumin-Induced Lung Inflammation. Biol Pharm Bull 29: 884-888.
Johansen F.E. and Brandtzaeg P. 2004. Transcriptional regulation of the mucosal IgA system. Trends Immunol 25: 150-157.
Kao, S.T., Wang, S.D., Wang, Y.J., Yu, C.K., and Lei, H.Y. 2000. The effect of Chinese herbal medicine, xiao-qing-long-tang (XQLT), on allergen-induced bronchial inflammation in mite-sensitized mice. Allergy 55: 1127-1133.
Karadag, B., Ege, M.J., Scheynius, A., Waser, M., Schram-Bijkerk, D., van Hage, M., Pershagen, G., Brunekreef, B., Riedler, J., Braun-Fahrländer, C., and von Mutius, E. 2007. Environmental determinants of atopic eczema phenotypes in relation to asthma and atopic sensitization. Allergy 62: 1387-1393.
Kay, A.B., Phipps, S., and Robinson, D.S. 2004. A role for eosinophils in airway remodelling in asthma. Trends Immunol 25: 477-482.
Kippelen, P., Caillaud, C., Coste, O., Godard, P., and Préfaut, C. 2004. Asthma and exercise-induced bronchoconstriction in amateur endurance-trained athletes. Int J Sports Med 25: 130-132.
Kips, J.C. 2001. Cytokines in asthma. Eur Respir J 18: 24s-33s.
Ko, E., Rho, S., Cho, C., Choi, H., Ko, S., Lee, Y., Hong, M.C., Shin, M.K., Jung, S.G., and Bae, H. 2004. So-Cheong-Ryong-Tang, tradititional Korean medicine, suppresses Th2 lineage development. Biol Pharm Bull 27: 739-743.
Krzanowski, J. and Polson, J.B. 1988. Mechanism of action of methylxanthines in asthma. J Allergy Clin Immunol 82: 143-145.
La, C.B., Molgaard, P., and Yi, Z. 1995. Traditional Chinese medicine in treatment of hyperlipidaemia. J Ethnopharmacol 46: 125-129.
Lanski, S.L., Greenwald, M., Perkins, A., and Simon, H.K. 2003. Herbal therapy use in a pediatric emergency department population: expect the unexpected. Pediatrics 111: 981-985.
Larché, M., Robinson, D.S., and Kay, A.B. 2003. The role of T lymphocytes in the pathogenesis of asthma. J Allergy Clin Immunol 111: 450-463.
Lee, J.J., McGarry, M.P., Farmer, S.C., Denzler, K.L., and Larson, K.A. 1997. Interleukin-5 expression in the lung epithelium of transgenic mice leads to pulmonary changes pathognomonic of asthma. J Exp Med 185: 2143-2156.
Lee, J.Y., Lee, Y.D., Bahn, J.W., and Park, H.S. 2006. A case of occupational asthma and rhinitis caused by Sanyak and Korean ginseng dusts. Allergy 61: 392-393.
Lee, Y.C., Lee, J.C., Seo, Y.B., and Kook, Y.B. 2005. Liriopis tuber inhibit OVA-induced airway inflammation and bronchial hyperresponsiveness in murine model of asthma. J Ethnopharmacol 101: 144-152.
Leigh, R., Ellis, R., Wattie, J., Hirota, J., Matthaei, K., Foster, P., O'Byrne, P., and Inman, M. 2004. Type 2 cytokines in the pathogenesis of sustained airway

dysfunction and airway remodeling in mice. Am J Respir Crit Care Med 169: 860-867.
Li, M., Zhang, H., and Yang, B. 1997. Efects of Ginkgo leaf concentrated oral liquor in treating asthma. Chung Kou Ching Hsi I Chieh Ho Tsa Chih 17: 216-218.
Li, X.M., Huang, C.K., Zhang, T.F., Teper, A.A., Srivastava, K., Schofield, B.H., and Sampson, H.A. 2000. The chinese herbal medicine formula MSSM-002 suppresses allergic airway hrperrecativity and modulates Th1/Th2 responses in a murine model of allergic asthma. J Allergy Clin Immunol 106: 660-668.
Li, X.M., Zhang, T.F., Sampson, H., Zou, Z.M., Beyer, K., Wen, M.C., and Schofield, B. 2004. The potential use of Chinese herbal medicines in treating allergic asthma. Ann Allergy Asthma Immunol 93: S35-44.
Lin, C.C., Huang, P.C., and Lin, J.M. 2000. Antioxidant and hepatoprotective effects of Anoectochilus formosanus and Gynostemma pentaphyllum. Am J Chin Med 28: 87-96.
Lin, J.M., Lin, C.C., Chiu, H.F., Yang, J.J., and Lee, S.G. 1993. Evaluation of the anti-inflammatory and liver-protective effects of Anoectochilus formosanus, Ganoderma lucidum and Gynostemma pentaphyllum in rats. Am J Chin Med 21: 59-69.
Liou, C.J., Li, M.L., and Tseng, J. 2004. Intraperitoneal injection of ginseng extract enhances both immunoglobulin and cytokine production in mice. Am J Chin Med 32:75-88.
Liu, A.H. 2002. Endotoxin exposure in allergy and asthma: reconciling a paradox. J Allergy Clin Immunol 109: 379-392.
Liu, R., Liu, Z.L., Li, Q., Qiu, Z.M., Lu, H.J., Yang, Z.M., and Hong, G.C. 2004. The experimental study on the inhibitory effect of tripterine on airway inflammation in asthmatic mice. Zhonghua Jie He He Hu Xi Za Zhi 27: 165-168.
Maa, S.H., Sun, M.F., Hsu, K.H., Hung, T.J., Chen, H.C., Yu, C.T., Wang, C.H., and Lin, H.C. 2003. Effect of acupuncture or acupressure on quality of life of patients with chronic obstructive asthma: a pilot study. J Altern Complement Med 9: 659-670.
Mamchak, A.A. and Hodgkin, P.D. 1995. The one signal theory of B cell activation revisited: a role for surface immunoglobulin in regulating T-independent antibody responses? Immunol Cell Biol 73: 266-271.
Marone, G., Triggiani, M., Genovese, A., and Paulis, A.D. 2005. Role of human mast cells and basophils in bronchial asthma. Adv Immunol 88: 97-160.
Marsha, W.K. 1999. Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol 17: 255-281.
Mayer, L.P., Dyer, C.A., Eastgard, R.L., Hoyer, P.B., and Banka, C.L. 2005. Atheroclerotic lesion development in a novel ovary-intact mouse model of perimenopause. . Arterioscler Thromb Vasc Biol 25: 1910-1916.
McKenzie, A.N.J. 2000. Regulation of T helper type 2 cell immunity by interleukin-4 and interleukin-13. Pharmacol Therapeut 88: 143-151.
McLeish, S. and Turner, S.W. 2007. Gene-environment interactions in asthma. Arch Dis Child 92: 1032-1035.
Megalli, S., Aktan, F., Davies, N.M., and Roufogalis, B.D. 2005. Phytopreventative anti-hyperlipidemic effects of Gynostemma pentaphyllum in rats. J Pharm Pharm Sci 8: 507-815.
Mocellin, S., Panelli, M.C., Wang, E., Nagorsen, D., and Marincola, F.M. 2003. The dual role of IL-10. Trends Immunol 24: 36-43.
Munitz, A. and Levi-Schaffer, F. 2004. Eosinophils: `new` roles for `old` cells. Allergy 59: 268-275.
Murphy, V.E., Gibson, P.G., Smith, R., and Clifton, V.L. 2005. Asthma during pregnancy: mechanisms and treatment implications. Eur Respir J 25: 731 -750.
Nagai, T., Arai, Y., Emori, M., Nunome, S.U., Yabe, T., Takeda, T., and Yamada, H. 2004. 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 4 1353–1365.
Nakashima, K., Hirota, T., Obara, K., Shimizu, M., Doi, S., Fujita, K., Shirakawa, T., Enomoto, T., Yoshihara, S., Ebisawa, M., Matsumoto, K., Saito, H., Suzuki, Y., Nakamura, Y., and Tamari, M. 2006. A functional polymorphism in MMP-9 is associated with childhood atopic asthma. Biochem Biophys Res Commun 344: 300-307.
Neurath, M.F., Finotto, S., and Glimcher, L.H. 2002. The role of Th1/Th2 polarization in mucosal immunity. Nat Med 8: 567-573.
Niven, A.S. and Gregory, A. 2003. Alternate treatments in asthma. Chest 123: 1254 -1265.
Norberg, A., Hoa, N.K., Liepinsh, E., Van Phan, D., Thuan, N.D., Jornvall, H., Sillard, R., and Ostenson, C.G. 2004. A novel insulin-releasing substance, phanoside, from the plant Gynostemma pentaphyllum. J Biol Chem 279: 41361-41367.
Pilette, C., Ouadrhiri, Y., Godding, V., Vaerman, J.P., and Sibille, Y. 2001. Lung mucosal immunity: immunoglobulin-A revisited. . Eur Respir J 18: 571-588.
Randhawa, I. and Klaustermeyer, W.B. 2007. Oral corticosteroid-dependent asthma: a 30-year review. Ann Allergy Asthma Immunol 99: 291-302.
Razmovski-Naumovski, V., Huang, T.S.W., Tran, V.H., Li, G.Q., Duke, C.C., and Roufogalis, B.D. 2005 Chemistry and pharmacology of Gynostemma pentaphyllum. Phytochemistry Reviews 4: 197-219.
Riccioni, G., Bucciarelli, T., Mancini, B., Di, I.E., Palumbo, G., and D'Orazio, N. 2007. Compliance therapy with anti-inflammatory antiasthmatic drugs: inhaled corticosteroids and leukotriene receptor antagonists. Clin Ter 158: 363-370.
Roche, W.R., Beasley, R., Williams, J.H., and Holgate, S.T. 1989. Subepithelial fibrosis in the bronchi of asthmatics. Lancet 1: 520-524.
Rodrigo, G.J., Rodrigo, C., and Hall, J.B. 2004. Acute Asthma in Adults: A Review. Chest 125: 1081-1102.
Roh, G.S., Seo, S.W., Yeo, S., Lee, J.M., Choi, J.W., Kim, E., Shin, Y., Cho, C., Bae, H., Jung, S.K., and Kwack, K. 2005. Efficacy of a traditional Korean medicine, Chung-Sang-Bo-Ha-Tang, in a murine model of chronic asthma. Int Immunopharmacol 5: 427-436.
Romagnani, S. 1997. The Th1/Th2 paradigm. Immunol Today 18: 263-266.
Romagnani, S. 2004. Immunologic influences on allergy and the TH1/TH2 balance. J Allergy Clin Immunol 113: 395-400.
Rothenberg, M.E. and Hogan, S.P. 2006. The eosinophil. Annu Rev Immunol 24: 147-174.
Rujjanawate, C., Kanjanapoth, i.D., and Amornlerdpison, D. 2004. The anti-gastric ulcer effect of Gynostemma pentaphyllum Makino. Phytomedicine 11: 431-435.
Saetta, M. and Turato, G. 2001. Airway pathology in asthma. Eur Respir J 18: 18s-23s.
Salvatoni, A., Piantanida, E., and Nosetti, L. 2003. Inhaled corticosteroids in childhood asthma: long-term effects on growth and adrenocortical function. Paediatr Drugs 5: 351-361.
Sanak, M., Potaczek, D.P., Nizankowska-Mogilnicka, E., and Szczeklik, A. 2007. Genetic Variability of the High-affinity IgE Receptor alpha Subunit (FcepsilonRIalpha) is Related to Total Serum IgE levels in Allergic Subjects. Allergol Int 56: 397-401.
Sanderson, C.J. 1992. Interleukin-5, eosinophils, and disease. Blood 79: 3101-3109.
Scichilone, N., Messina, M., Battaglia, S., Catalano, F., and Bellia, V. 2005. Airway hyperresponsiveness in the elderly: prevalence and clinical implications. Eur Respir J 25: 364-375.
Shi, H.S., Xiao, C.Q., Li, C.Q., Mo, X.Y., Yang, Q.L., and Leng, J. 2004. Endobronchial eosinophils preferentially stimulate T helper cell type 2 responses. Allergy 59: 428-435.
Shen, H.H., Wang, K., Li, W., Ying, Y.H., Gao, G.X., Li, X.B., and Huang, H.Q.
2008 Astragalus Membranaceus prevents airway hyperreactivity in mice related to Th2 response inhibition. J Ethnopharmacol. 116:363-369.
Singh, B.B., Khorsan, R., Vinjamury, S.P., Dr-Martirosian, C., Kizhakkeveettil, A., and Anderson, T.M. 2007. Herbal treatments of asthma: a systematic review. J Asthma 44: 685-698.
Smith, K.A. 1988. Interleukin-2: inception, impact, and implications. Science 240: 1169-1176.
Sonobe, Y., Nakane, H., Watanabe, T., and Nakano, K. 2004. Regulation of Con A-dependent cytokine production from CD4+ and CD8+ T lymphocytes by autosecretion of histamine. Inflamm Res 53: 87-92.
Soussi-Gounni, A., Kontolemos, M., and Hamid, Q. 2001. Role of IL-9 in the pathophysiology of allergic diseases. J Allergy Clin Immunol 107: 575-582.
Srivastava, K., Teper, A.A., Zhang, T.F., Li, S., Walsh, M.J., Huang, C.K., Kattan, M., Schofield, B.H., Sampson, H.A., and Li, X.M. 2003. Immunomodulatory effect of the antiasthma chinese herbal formula MSSM-002 on the Th2 cell. J Allergy Clin Immunol 113: 268-276.
Tanaka, H., Komai, M., Nagao, K., Ishizaki, M., Kajiwara, D., Takatsu, K., Takatsu, K., Delespesse, G., and Nagai, H. 2004. Role of IL-5 and eosinophils in allergen induced airway remodeling in mice Am J Respir Cell Mol Biol 31: 62-68.
Toews, G.B. 2001. Cytokines and the lung. Eur Respir J 18: Suppl. 34:33s-17s.
Tsai, H.J. and Tsai, A.C. 2007. The association of diet with respiratory symptoms and asthma in schoolchildren in taipei, Taiwan. J Asthma 44: 599-603.
Valentina, R.N., Huang, T.S.W., Tran, V.H., Li, G.Q., Duke, C.C., and Roufogalis, B.D. 2005 Chemistry and pharmacology of Gynostemma pentaphyllum. Phytochem Rev 4: 197-219.
Vauloup-Fellous, C. and Grangeot-Keros, L. 2006. Humoral immune response after primary rubella virus infection and after vaccination. Clin Vaccine Immunol 14: 644-647.
Venkayya, R., Lam, M., Willkom, M., Grünig, G., Corry, D.B., and Erle, D.J. 2002. The Th2 lymphocyte products IL-4 and IL-13 rapidly induce airway hyperresponsiveness through direct effects on resident airway cells. Am J Respir Cell Mol Biol 26: 202-208.
Vermeer PD, Harson R, Einwalter LA, Moninger T, and Joseph., Z. 2003. Interleukin-9 induces goblet cell hyperplasia during repair of human airway epithelia. Am J Respir Cell Mol Biol 28: 286-295.
Wang, Q.F., Chen, J.C., Hsieh, S.J., Cheng, C.C., and Hsu, S.L. 2002. Regulation of Bcl-2 family molecules and activation of caspase cascade involved in gypenosides-induced apoptosis in human hepatoma cells.
Cancer Lett 183: 169-178.
Wang, W., Halmurat, W., Yilihamu, S., Xiang, Y.B., and Ablikemu, A. 2004. A study on the relationship between interleukin-4 promoter polymorphism and asthma in a Xinjiang Uyger population. Zhonghua Jie He He Hu Xi Za Zhi 27: 460-464.
Weiss, S.T. and Raby, B.A. 2004. 2003 Asthma genetics. Hum Mol Genet 13: 83 - 89.
Wen, M.C., Wei, C.H., Hu, Z.Q., Srivastava, K., Ko, J., Xi, S.T., Mu, D.Z., Du, J.B., Li, G.H., Wallenstein, S., Sampson, H., Kattan, M., and Li, X.M. 2005 Efficacy and tolerability of anti-asthma herbal medicine intervention in adult patients with moderate-severe allergic asthma. J Allergy Clin Immunol 116: 517-524.
Wills-Karp, M. 1999. Immunologic basis of antigen-induced airway induced hyperresponsiveness. Annu Rev Immunol 17: 255-281.
Wills-Karp, M. 2004. Interleukin-13 in asthma pathogenesis. Immunol Rev 202: 175-190.
Xystrakis, E., Kusumakar, S., Boswell, S., Peek, E., Urry, Z., and Richards, D.F. 2006. Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. J Clin Invest 116: 146-155.
Yadav, R.K., Ray, R.B., Vempati, R., and Bijlani, R.L. 2005. Effect of a comprehensive yoga-based lifestyle modification program on lipid peroxidation. Indian J Physiol Pharmacol 49: 358-362.
Yang, C.Y., Chen, C.C., Chen, C.Y., and Kuo, H.W. 2007a. Air pollution and hospital admissions for asthma in a subtropical city: Taipei, Taiwan. J Toxicol Environ Health 70: 111-117.
Yang, Z., Chen, A., Sun, H., Ye, T., and Fang, W. 2007b. Ginsenoside Rd elicits Th1 and Th2 immune responses to ovalbumin in mice Vaccine 25: 161-169

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