18β-glycyrrhetinic acid induces immunological adjuvant activity of Th1 against Candida albicans surface mannan extract

Phytomedicine. 2013 Aug 15;20(11):951-5. doi: 10.1016/j.phymed.2013.04.008. Epub 2013 Jun 7.

Abstract

The aim of this study was to determine the immunological adjuvant effect of 18β-glycyrrhetinic acid (GA) isolated from Glycyrrhizae radix. In the experiments, BALB/c mice were immunized on days 1 and 22 intraperitoneally (i.p.) with an emulsion form of Candida albicans surface mannan extract (SM) mixed with either Incomplete Freund's Adjuvant [SM/IFA], or Complete Freund's Adjuvant [SM/CFA] or GA mixed with IFA [SM/GA/IFA]. One week after the second immunization, polyclonal sera were collected from these animals in order to determine IgG isotypes and cytokine profiles in the sera. After the collection, the spleen samples were collected to determine the degree of T cell proliferation. Additionally, the DTH (delayed type hypersensitivity) response was examined by measuring the footpad swelling of immunized mice. Data resulting from the T cell proliferation test showed that SM/GA/IFA enhanced the proliferation the most. The enhancement was about 85% more compared to SM/IFA (p<0.05). IgG isotypes and cytokine profiles displayed that SM/GA/IFA induced the most abundant production of total IgG with the highest IgG2a/IgG1 ratio (1.31) and greatest IFN-γ secretion. In contrast, SM/CFA resulted in an IgG2a/IgG1 ratio less than 1 and SM/IFA produced a dominant induction of IL-4, but almost no IFN-γ secretion. Together, these observations revealed that GA developed a greater Th1 immune response than Th2 response. The DTH determination confirmed that GA-addition induced dominant Th1 immunity - displaying the highest footpad-swelling followed by SM/CFA and BSA/IFA, respectively. All of this data indicates that GA has a Th1-immunological adjuvant activity, which would be beneficial in the treatment of Th1-disordered disease due to C. albicans.

Keywords: 18β-Glycyrrhetinic acid; Adjuvant; C. albicans; Mice; Th1/Th2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • Candida albicans / immunology*
  • Candida albicans / metabolism
  • Candidiasis / blood
  • Candidiasis / drug therapy
  • Candidiasis / immunology*
  • Cell Proliferation / drug effects
  • Edema
  • Female
  • Freund's Adjuvant
  • Glycyrrhetinic Acid / analogs & derivatives*
  • Glycyrrhetinic Acid / immunology
  • Glycyrrhetinic Acid / pharmacology
  • Glycyrrhetinic Acid / therapeutic use
  • Glycyrrhiza / chemistry*
  • Hypersensitivity, Delayed / drug therapy
  • Hypersensitivity, Delayed / immunology
  • Hypersensitivity, Delayed / pathology
  • Immunization
  • Immunoglobulin G / blood
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Lipids
  • Mannans / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Phytotherapy
  • Plant Extracts / immunology
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Spleen / immunology
  • Th1 Cells / metabolism*
  • Th1-Th2 Balance / drug effects
  • Th2 Cells / metabolism

Substances

  • Adjuvants, Immunologic
  • Immunoglobulin G
  • Lipids
  • Mannans
  • Plant Extracts
  • incomplete Freund's adjuvant
  • 18alpha-glycyrrhetinic acid
  • Interleukin-4
  • Interferon-gamma
  • Freund's Adjuvant
  • Glycyrrhetinic Acid