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Journal of Integrative Medicine: Volume 11, 2013   Issue 3,  Pages: 195-205

DOI: 10.3736/jintegrmed2013029
Research Article
Constituents of the anti-asthma herbal formula ASHMITM synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro
1. Bolleddula Jayaprakasam (Center for Chinese Herbal Therapy for Asthma and Allergy, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA )
2. Nan Yang (Center for Chinese Herbal Therapy for Asthma and Allergy, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA )
3. Ming-Chun Wen (Department of Pneumology, Weifang Asthma Hospital, Weifang 261041, Shandong Province, China )
4. Rong Wang (Department of Human Genetics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA )
5. Joseph Goldfarb (Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA )
6. Hugh Sampson (Center for Chinese Herbal Therapy for Asthma and Allergy, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA )
7. Xiu-Min Li (Center for Chinese Herbal Therapy for Asthma and Allergy, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA E-mail: xiu-min.li@mssm.edu)

OBJECTIVE: Anti-asthma herbal medicine intervention (ASHMITM), a combination of three traditional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMITM exhibited synergy.

METHODS: Effects of ASHMI and its components aqueous extracts of Lingzhi (Ganoderma lucidum), Kushen (Sophora flavescens) and Gancao (Glycyrrhiza uralensis), on Th2 cytokine secretion by murine memory Th2 cells (D10.G4.1) and eotaxin-1 secretion by human lung fibroblast (HLF-1) cells were determined by measuring levels in culture supernatants by enzyme-linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters.

RESULTS: Individual Lingzhi, Kushen and Gancao extracts and ASHMI (the combination of individual extracts) inhibited production of interleukin (IL)-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration (IC25) values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50 values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-1. The interaction indices at IC50 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC50 values. All interaction indices were below 1 which indicated synergy.

CONCLUSION: By comparing the interaction index values, we find that constituents in ASHMITM synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.

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Please cite this article as:
Jayaprakasam B, Yang N, Wen MC, Wang R, Goldfarb J, Sampson H, Li XM. Constituents of the anti-asthma herbal formula ASHMITM synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro. J Integr Med. 2013; 11(3): 195-205.
1Centers for Disease Control and Prevention. National Center for Health Statistics: Asthma 2011. [2012-01-18]. http://www.cdc.gov/nchs/fastats/asthma.htm.
2Eid N, Morton R, Olds B, Clark P, Sheikh S, Looney S. Decreased morning serum cortisol levels in children with asthma treated with inhaled fluticasone propionate[J].Pediatrics, 2002, 109(2): 217-221.  
3Visser MJ, van der Veer E, Postma DS, Arends LR, de Vries TW, Brand PL, Duiverman EJ. Side-effects of fluticasone in asthmatic children: no effects after dose reduction[J].Eur Respir J, 2004, 24(3): 420-425.  
4Wen MC, Wei CH, Hu ZQ, Srivastava K, Ko J, Xi ST, Mu DZ, Du JB, Li GH, Wallenstein S, Sampson H, Kattan M, Li XM. Efficacy and tolerability of anti-asthma herbal medicine intervention in adult patients with moderate-severe allergic asthma[J].J Allergy Clin Immunol, 2005, 116(3): 517-524.  
5Li XM. Complementary and alternative medicine in pediatric allergic disorders[J].Curr Opin Allergy Clin Immunol, 2009, 9(2): 161-167.  
6Hsu CH, Lu CM, Chang TT. Efficacy and safety of modified Mai-Men-Dong-Tang for treatment of allergic asthma[J].Pediatr Allergy Immunol, 2005, 16(1): 76-81.  
7Chan CK, Kuo ML, Shen JJ, See LC, Chang HH, Huang JL. Ding Chuan Tang, a Chinese herb decoction, could improve airway hyper-responsiveness in stabilized asthmatic children: a randomized, double-blind clinical trial[J].Pediatr Allergy Immunol, 2006, 17(5): 316-322.  
8Chang TT, Huang CC, Hsu CH. Clinical evaluation of the Chinese herbal medicine formula STA-1 in the treatment of allergic asthma[J].Phytother Res, 2006, 20(5): 342-347.  
9Busse PJ, Srivastava K, Wei CH, Li GH, Yu N, Liu YH, Wallenstein S, Wisnivesky J, Qu C, Sampson H, Li XM. Safety, tolerability and beneficial immunological responses of complementary ASHMI therapy to inhaled corticosteroids therapy in children with persistent allergic asthma with or without allergic rhinitis[J].Allergy Clin Immunol, 2010, 125(2): S199.  
10Srivastava K, Zhang T, Yang N, Sampson H, Li XM. Anti-Asthma Simplified Herbal Medicine Intervention-induced long-lasting tolerance to allergen exposure in an asthma model is interferon-gamma, but not transforming growth factor-β dependent[J].Clin Exp Allergy, 2010, 40(11): 1678-1688.  
11Zhang T, Srivastava K, Wen MC, Yang N, Cao J, Busse P, Birmingham N, Goldfarb J, Li XM. Pharmacology and immunological actions of a herbal medicine ASHMI on allergic asthma[J].Phytother Res, 2010, 24(7): 1047-1055.  
12Bensky D, Barolet R. Chinese herbal medicine: formulas and strategies. Seattle: Eastland Press. 1990.
13Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals[J].Phytomedicine, 2009, 16(2-3): 97-110.  
14Hosoya E, Yamamura Y. Recent advances in the pharmacology of Kampo (Japanese herbal) medicines[M]. Tokyo: Excerpta Medica, 1998. 260.  
15Busse PJ, Schofield B, Birmingham N, Yang N, Wen MC, Zhang T, Srivastava K, Li XM. The traditional Chinese herbal formula ASHMI inhibits allergic lung inflammation in antigen-sensitized and antigen-challenged aged mice[J].Ann Allergy Asthma Immunol, 2010, 104(3): 236-246.  
16Kaye J, Porcelli S, Tite J, Jones B, Janeway CA. Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells[J].J Exp Med, 1983, 158(3): 836-856.  
17Srivastava K, Teper AA, Zhang TF, Li S, Walsh MJ, Huang CK, Kattan M, Schofield BH, Sampson HA, Li XM. Immunomodulatory effect of the anti-asthma Chinese herbal formula, MSSM-002 on Th2 cells[J].J Allergy Clin Immunol, 2004, 113(2): 268-276.  
18Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment[J].Cell, 2000, 100(6): 655-669.  
19Conroy DM, Williams TJ. Eotaxin and the attraction of eosinophils to the asthmatic lung[J].Respir Res, 2001, 2(3): 150-156.  
20Sato E, Nelson DK, Koyama S, Hoyt JC, Robbins RA. Inflammatory cytokines modulate eotaxin release by human lung fibroblast cell line[J].Exp Lung Res, 2001, 27(2): 173-183.  
21Jayaprakasam B, Doddaga S, Wang R, Holmes D, Goldfarb J, Li XM. Licorice flavonoids inhibit eotaxin-1 secretion by human fetal lung fibroblasts in vitro[J].J Agric Food Chem, 2009, 57(3): 820-825.  
22Matsui S, Matsumoto H, Sonoda Y, Ando K, Aizu-Yokota E, Sato T, Kasahara T. Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line[J].Int Immunopharmacol, 2004, 4(13): 1633-1644.  
23Matsui S, Sonoda Y, Sekiya T, Aizu-Yokota E, Kasahara T. Glycyrrhizin derivative inhibits eotaxin 1 production via STAT6 in human lung fibroblasts[J].Int Immunopharmacol, 2006, 6(3): 369-375.  
24Chinese Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China. Beijing: People’s Medical Publishing House. 2005.
25Kelly-Pieper K, Patil SP, Busse P, Yang N, Sampson H, Li XM, Wisnivesky JP, Kattan M. Safety and tolerability of an antiasthma herbal formula (ASHMI) in adult subjects with asthma: a randomized, double-blinded, placebo-controlled, dose-escalation phase I study[J].J Altern Complement Med, 2009, 15(7): 735-743.  
26U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for industry: botanical drug products (Revised). 2004.
27Li XM, Brown L. Efficacy and mechanisms of action of traditional Chinese medicines for treating asthma and allergy[J].J Allergy Clin Immunol, 2009, 123(2): 297-306.  
28Ministry of Foreign Trade and Economic Cooperation PRC. Green trade standards of importing & exporting medicinal plants & preparations. 2001. Chinese.
29Raman P, Patino LC, Nair MG. Evaluation of metal and microbial contamination in botanical supplements[J].J Agric Food Chem, 2004, 52(26): 7822-7827.  
30Dolan SP, Nortrup DA, Bolger PM, Capar SG. Analysis of dietary supplements for arsenic, cadmium, mercury, and lead using inductively coupled plasma mass spectrometry[J].J Agric Food Chem, 2003, 51(5): 1307-1312.  
31Caldas ED, Machado LL. Cadmium, mercury and lead in medicinal herbs in Brazil[J].Food Chem Toxicol, 2004, 42(4): 599-603.  
32Li XM, Schofield BH, Wang QF, Kim KH, Huang SK. Induction of pulmonary allergic responses by antigen-specific Th2 cells[J].J Immunol, 1998, 160(3): 1378-1384.  
33Jayaprakasam B, Zhang Y, Seeram NP, Nair MG. Growth inhibition of human tumor cell lines by withanolides from Withania somnifera leaves[J].Life Sci, 2003, 74(1): 125-132.  
34Berenbaum MC. Criteria for analyzing interactions between biologically active agents[J].Adv Cancer Res, 1981, 35: 269-335.  
35Liu C, Yang N, Folder W, Cohn J, Wang R, Li X. Ganoderic acid C isolated from Ganoderma lucidum suppresses LPS-induced macrophage TNF-α production by down-regulating MAPK, NF-kappaB and AP-1 signaling pathways[J].J Allergy Clin Immunol, 2012, 129(2): S127.  
36Mould AW, Ramsay AJ, Matthaei KI, Young IG, Rothenberg ME, Foster PS. The effect of IL-5 and eotaxin expression in the lung on eosinophil trafficking and degranulation and the induction of bronchial hyperreactivity[J].J Immunol, 2000, 164(4): 2142-2150.  
37Kan WL, Cho CH, Rudd JA, Lin G. Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells[J].J Ethnopharmacol, 2008, 120(1): 36-43.  
38Gao JL, He TC, Li YB, Wang YT. A traditional Chinese medicine formulation consisting of Rhizoma Corydalis and Rhizoma Curcumae exerts synergistic anti-tumor activity[J].Oncol Rep, 2009, 22(5): 1077-1083.  
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