Asthma, a chronic inflammatory lung disease, is a worldwide major public health problem, which currently affects 15 million people in the United States. Although corticosteroids are widely used for asthma treatment, their side effects are a significant concern, particularly for children. The need for safe and effective treatments of this disease is urgent. Chinese herbal therapy (CHT) used for thousands of years, has been suggested to have a potential for treating allergies and asthma. However, a role for CHT in asthma therapy remains to be established because there are few well-controlled scientific studies demonstrating its efficacy, safety and mechanisms of action. During our R21 grant period we generated an asthma herbal medicine intervention ASHMI (composed of 3 herbs) derived from the original anti asthma formula MSSM-002 (composed of 14 herbs). This development makes herbal formula quality control less difficult. We demonstrated in a well-characterized murine model of chronic allergic asthma that ASHMI exhibits a broad spectrum of therapeutic effects on the major pathogenesis of asthma, including AHR, pulmonary inflammation, airway remodeling, which was associated with its down-regulation Th2 responses, indicating a potential for developing as an asthma therapy. In this project, we will evaluate in depth the therapeutic effects and mechanisms of the herbal formula ASHMI on a well-characterized murine model of allergic asthma. Pharmacological effects on AHR, inflammation, airway remodeling, airway smooth muscle contractility, and effector memory T cell cytokine secretion as well as a long lasting therapeutic effect will be determined using a range of physiological, immunological and molecular biology measurements in vivo and in vitro. Because we have determined that this formula suppresses Th2 cytokine secretion in a non-toxic manner, we will investigate the molecular mechanisms underlying the effect by focusing on the Th2 transcription factor GATA-3. In collaboration with Project #3, we will investigate individual bioactive constituents and assess their synergistic effects in ASHMI extract on allergic airway responses. Accomplishing this study will be of fundamental importance to validate the possible pharmacological actions of Chinese herbal medicine on allergic asthma, and provide advanced understanding of the immunotherapeutic mechanisms underlying ASHMI effects on allergic asthma. Ultimately, this study along with the studies addressed in other projects of this center grant may lead to a novel approach-botanical drug for treating asthma and perhaps other allergic inflammatory disease.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Program Projects (P01)
Project #
5P01AT002647-04
Application #
7496136
Study Section
Special Emphasis Panel (ZAT1-G (15))
Program Officer
Pontzer, Carol H
Project Start
2005-09-30
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
4
Fiscal Year
2008
Total Cost
$1,154,922
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Pediatrics
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
López-Expósito, Iván; Srivastava, Kamal D; Birmingham, Neil et al. (2015) Maternal Antiasthma Simplified Herbal Medicine Intervention therapy prevents airway inflammation and modulates pulmonary innate immune responses in young offspring mice. Ann Allergy Asthma Immunol 114:43-51.e1
Liu, Changda; Weir, David; Busse, Paula et al. (2015) The Flavonoid 7,4'-Dihydroxyflavone Inhibits MUC5AC Gene Expression, Production, and Secretion via Regulation of NF-?B, STAT6, and HDAC2. Phytother Res 29:925-32
Liu, Changda; Dunkin, David; Lai, Joanne et al. (2015) Anti-inflammatory Effects of Ganoderma lucidum Triterpenoid in Human Crohn's Disease Associated with Downregulation of NF-?B Signaling. Inflamm Bowel Dis 21:1918-25
Liu, Changda; Yang, Nan; Song, Ying et al. (2015) Ganoderic acid C1 isolated from the anti-asthma formula, ASHMI™ suppresses TNF-? production by mouse macrophages and peripheral blood mononuclear cells from asthma patients. Int Immunopharmacol 27:224-31
Srivastava, Kamal D; Dunkin, David; Liu, Changda et al. (2014) Effect of Antiasthma Simplified Herbal Medicine Intervention on neutrophil predominant airway inflammation in a ragweed sensitized murine asthma model. Ann Allergy Asthma Immunol 112:339-47.e1-2
Birmingham, J M; Gillespie, V L; Srivastava, K et al. (2014) Influenza A infection enhances antigen-induced airway inflammation and hyperresponsiveness in young but not aged mice. Clin Exp Allergy 44:1188-99
Yang, Nan; Liang, Banghao; Srivastava, Kamal et al. (2013) The Sophora flavescens flavonoid compound trifolirhizin inhibits acetylcholine induced airway smooth muscle contraction. Phytochemistry 95:259-267
Birmingham, Janette M; Patil, Sangita; Li, Xiu-Min et al. (2013) The effect of oral tolerance on the allergic airway response in younger and aged mice. J Asthma 50:122-32
Jayaprakasam, Bolleddula; Yang, Nan; Wen, Ming-Chun et al. (2013) Constituents of the anti-asthma herbal formula ASHMI(TM) synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro. J Integr Med 11:195-205
Srivastava, Kamal; Sampson, Hugh A; Emala Sr, Charles W et al. (2013) The anti-asthma herbal medicine ASHMI acutely inhibits airway smooth muscle contraction via prostaglandin E2 activation of EP2/EP4 receptors. Am J Physiol Lung Cell Mol Physiol 305:L1002-10

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