Suppression of severe airway inflammation with non-toxic dietary nutrients in histamine-challenged guinea pigs: A comparison with Ibuprofen

Authors

Abstract

We hypothesize that selected combinations of nutrients commonly encountered in the human diet, suppress asthma-associated airway inflammation more effectively than currently available anti-inflammatory medications. Here we demonstrate that biflavones and terpenes, distributed widely in human diet (in this case derived from Ginkgo biloba) synergize with the carotenoid antioxidant astaxanthin and vitamin C to suppress asthma-associated inflammation in a guinea pig model.
Male Hartley guinea pigs treated with 10-1000 mg/kg Ibuprophen, or: EGb761 (0-100 mg/kg), astaxanthin (0-200 mg/kg), vitamin C (0-400 mg/kg), or combinations thereof, were ovalbumin sensitized, then challenged with ovalbumin aerosol to induce asthma. Each animal was evaluated for inflammation-associated indicators. Differential cell counts were performed on bronchoalveolar fluid using standard morphologic criteria to classify cells as eosinophils, neutrophils, or macrophages. Cyclic nucleotide (cAMP and cGMP) content in lung tissue was measured using radioimmunoassay.
Each disease indicator was significantly altered to a greater degree by combinations of drugs, than by components acting independently, or by Ibuprophen. Optimal combinations were identified that included astaxanthin (10 mg/kg), vitamin C (200 mg/kg), and EGb761 (10 mg/kg), resulting in counts of eosinophils and neutrophils each 1.6-fold lower; macrophages 1.8-fold lower, cAMP 1.4-fold higher; and cGMP 2.04-fold higher than levels in untreated animals (p<0.05).
We show that selcted dosage combinations of common dietary nutrients are highly effective in suppressing inflammation. These formulations: i. suppress pathogenic T cell activation; ii. inhibit inflammatory mediator release; and iii. quench reactive oxygen. These three processes underly pathogenesis of all inflammatory disease. Current pharmacological strategies typically target only a limited aspect of these pathways (such as COX-2 or histamine activity). Conversely we suppress all simultaneously. It is anticipated that this approach will be particularly valuable in treatment of chronic airway disease associated with exposure to chemical weapons, in particular, ”Mustard Lung” a chronic disorder seen in mustard agent victims.

Iranian Journal of Pharmaceutical Research (2004): Supplement 2

Iranian Journal of Pharmaceutical Research (2004): Supplement 2: 24-24
Oral Presentations

2nd International Congress on Traditional Medicine and Materia Medica
October 4-7, 2004, Tehran, Iran

65

Suppression of severe airway inflammation with non-toxic dietary nutrients in histamine-challenged guinea pigs: A comparison with Ibuprofen

Haines D.D.1, Bak I.2, Giricz Z.3, Wise J.A.4, Ferdinandy P.5, Mahmoud F.6, Tosaki A.7

1Department Epidemiology and Biostatistics, The George Washington University Medical Center, Washington DC, USA 2Department Pharmacology, Helath Science Center, University of Debrecen, Debrecen, Hungary 3Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Hungary 4Natural Alternatives International Inc. San Marcos California, USA 5Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Hungary 6Department Medical Laboratory Sciences, Faculty of Allied Health Sciences & Nursing, Kuwait University 7Department Pharmacology, Helath Science Center, University of Debrecen, Debrecen, Hungary

We hypothesize that selected combinations of nutrients commonly encountered in the human diet, suppress asthma-associated airway inflammation more effectively than currently available anti-inflammatory medications. Here we demonstrate that biflavones and terpenes, distributed widely in human diet (in this case derived from Ginkgo biloba) synergize with the carotenoid antioxidant astaxanthin and vitamin C to suppress asthma-associated inflammation in a guinea pig model.

Male Hartley guinea pigs treated with 10-1000 mg/kg Ibuprophen, or: EGb761 (0-100 mg/kg), astaxanthin (0-200 mg/kg), vitamin C (0-400 mg/kg), or combinations thereof, were ovalbumin sensitized, then challenged with ovalbumin aerosol to induce asthma. Each animal was evaluated for inflammation-associated indicators. Differential cell counts were performed on bronchoalveolar fluid using standard morphologic criteria to classify cells as eosinophils, neutrophils, or macrophages. Cyclic nucleotide (cAMP and cGMP) content in lung tissue was measured using radioimmunoassay.

Each disease indicator was significantly altered to a greater degree by combinations of drugs, than by components acting independently, or by Ibuprophen. Optimal combinations were identified that included astaxanthin (10 mg/kg), vitamin C (200 mg/kg), and EGb761 (10 mg/kg), resulting in counts of eosinophils and neutrophils each 1.6-fold lower; macrophages 1.8-fold lower, cAMP 1.4-fold higher; and cGMP 2.04-fold higher than levels in untreated animals (p<0.05).

We show that selcted dosage combinations of common dietary nutrients are highly effective in suppressing inflammation. These formulations: i. suppress pathogenic T cell activation; ii. inhibit inflammatory mediator release; and iii. quench reactive oxygen. These three processes underly pathogenesis of all inflammatory disease. Current pharmacological strategies typically target only a limited aspect of these pathways (such as COX-2 or histamine activity). Conversely we suppress all simultaneously. It is anticipated that this approach will be particularly valuable in treatment of chronic airway disease associated with exposure to chemical weapons, in particular, ”Mustard Lung” a chronic disorder seen in mustard agent victims.

Presenting Author: Haines, D.D. ddhaines2002@yahoo.com