Piperine inhibits eosinophil infiltration and airway hyperresponsiveness by suppressing T cell activity and Th2 cytokine production in the ovalbumin-induced asthma model

J Pharm Pharmacol. 2009 Mar;61(3):353-9. doi: 10.1211/jpp/61.03.0010.

Abstract

Objectives: This study aimed to investigate the effect of piperine on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, immunoglobulin E and histamine production in a murine model of asthma.

Methods: Asthma was induced in Balb/c mice by ovalbumin sensitization and inhalation. Piperine (4.5 and 2.25 mg/kg) was orally administered 5 times a week for 8 weeks. At 1 day after the last ovalbumin exposure, airway hyperresponsiveness was determined and samples of bronchoalveolar lavage fluid, lung cells and serum were collected for further analysis.

Key findings: Piperine-treated groups had suppressed eosinophil infiltration, allergic airway inflammation and airway hyperresponsiveness, and these occurred by suppression of the production of interleukin-4, interleukin-5, immunoglobulin E and histamine. Moreover, polymerase chain reaction products for thymus and activation regulated chemokine from lung cell RNA preparations were decreased in the piperine-treated group compared with control groups, although transforming growth factor-beta products were increased in the piperine-treated group.

Conclusions: The results suggest that the therapeutic mechanism by which piperine effectively treats asthma is based on a reduction of Th2 cytokines (interleukin-4, interleukin-5), eosinophil infiltration, and by marked reduction of thymus and activation regulated chemokine, eotaxin-2 and interleukin-13 mRNA expression (especially transcription of nuclear factor-kappaB dependent genes) in lung tissue, as well as reduced interleukin-4, interleukin-5 and eotaxin levels in bronchoalveolar lavage fluid, and histamine and ovalbumin-specific immunoglobulin E production in serum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / administration & dosage
  • Alkaloids / pharmacology*
  • Animals
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Benzodioxoles / administration & dosage
  • Benzodioxoles / pharmacology*
  • Bronchial Hyperreactivity / drug therapy
  • Cytokines / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Eosinophils / drug effects
  • Eosinophils / metabolism
  • Female
  • Histamine / metabolism
  • Immunoglobulin E / drug effects
  • Immunoglobulin E / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / administration & dosage
  • Polyunsaturated Alkamides / pharmacology*
  • RNA, Messenger / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / metabolism

Substances

  • Alkaloids
  • Benzodioxoles
  • Cytokines
  • Piperidines
  • Polyunsaturated Alkamides
  • RNA, Messenger
  • Immunoglobulin E
  • Histamine
  • Ovalbumin
  • piperine