Flavonoids as Th1/Th2 cytokines immunomodulators: A systematic review of studies on animal models

Phytomedicine. 2018 May 15:44:74-84. doi: 10.1016/j.phymed.2018.03.057. Epub 2018 Mar 20.

Abstract

Background: Flavonoids are naturally occurring compounds, extensively distributed in plants. T helper (Th)1 and Th2 cytokines balance plays an essential role in the reaction of inflammatory, allergic and infectious processes and transplantation rejection.

Purpose: This systematic review focuses on various classes of flavonoids with a view to evaluate whether Th1/Th2 cytokine-mediated pathways of immunoenhancement could reduce immune overwhelming reactions.

Methods: Articles in English published from inception to December 2017 reporting flavonoids with immunomodulatory activity for the management of immune-mediated disorders were acquired from PubMed, EMBASE, Scopus and Web of Science and a animal experiments where Th1 and Th2 cytokines were investigated to assess the outcome of immunoregulatory therapy were included.

Chapters: 1809 publications were identified and 26 were included in this review. Ten articles described the effect of flavonoids on allergic inflammation in an animal model of asthma; eleven in vivo studies evaluated the immunomodulating and immunosuppressive effects of flavonoids on Th1/Th2 cytokines production and five reports described the regulatory role of flavonoids for Th1/Th2 cytokine responses to experimental arthritis and myocarditis. Modulation of Th1/Th2 cytokine balance, inhibition of eosinophil accumulation and remodeling of the airways and lungs, downregulation of Notch and PI3K signaling pathways, regulation of CD4 + /CD8 + lymphocytes ratio and decreasing inflammatory mediator expressions levels are among the most important immunopharmacological mechanisms for the retrieved flavonoids.

Conclusion: Naturally occurring flavonoids discussed in the present article have optimal immunomodulation to prevent immune-mediated disorders through management of Th1/Th2 cytokine balance.

Keywords: Cytokines; Flavonoids; Immunomodulatory; Inflammation; Plants; Th1/Th2 balance.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Asthma / drug therapy
  • Asthma / immunology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Flavonoids / pharmacology*
  • Hypersensitivity / drug therapy
  • Hypersensitivity / immunology
  • Immunologic Factors / pharmacology*
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Lung / drug effects
  • Lung / immunology
  • Lung / metabolism
  • Myocarditis / drug therapy
  • Myocarditis / immunology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th2 Cells / drug effects*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • Cytokines
  • Flavonoids
  • Immunologic Factors
  • Phosphatidylinositol 3-Kinases