Berberine Attenuates Inflammation Associated with Delayed-Type Hypersensitivity via Suppressing Th1 Response and Inhibiting Apoptosis

Inflammation. 2017 Feb;40(1):221-231. doi: 10.1007/s10753-016-0472-6.

Abstract

Berberine, one of the active alkaloids from Rhizoma Coptidis, has been indicated to have anti-inflammatory and immunosuppressive properties. The aim of this study was to determine the role of berberine on ovalbumin (OVA)-induced delayed-type hypersensitivity (DTH) and its potential mechanisms. Berberine treatment significantly reduced footpad swelling, inflammatory cells infiltration, anti-OVA IgG levels, IgE concentration in serum, and the tetramer+CD8+ cells. In homogenized footpad tissue, the production of Th1-mediated cytokines including IFN-γ, TNF-α, and IL-2 were suppressed following the administration of berberine. Detailed studies revealed that berberine prevented differentiation into Th1 cells in the OVA-primed lymphocytes, resulting from suppressing the expression of T-bet and secretion of IFN-γ but not IL-4. Concanavalin A stimulation assay and MTT assay also indicated inhibiting effect of berberine treatment on IFN-γ production and decreased cytotoxicity in lymphocytes proliferation, respectively. Additionally, berberine obviously decreased the cell apoptosis and enzymatic activity of caspase-3, which was further confirmed by the facts that berberine clearly lowered Bax/Bcl-2 ratio and expression of cleaved caspase-3 protein. On correlation analysis, the percentage of apoptotic cells showed a significant positive relationship with IFN-γ/IL-4 ratio of supernatant from footpad tissue in berberine-treated DTH mice. These results demonstrated that berberine attenuated Th1-mediated inflammation in OVA-induced DTH by curbing Th1 response and inhibiting cell apoptosis, suggesting a therapeutic potential for berberine for the treatment of type IV hypersensitivity.

Keywords: Th1 response; apoptosis; berberine; delayed-type hypersensitivity; inflammation.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents
  • Apoptosis / drug effects*
  • Berberine / pharmacology*
  • Berberine / therapeutic use
  • Cell Differentiation / drug effects
  • Cytokines / drug effects
  • Hypersensitivity, Delayed / pathology*
  • Immunosuppressive Agents
  • Inflammation / drug therapy*
  • Mice
  • Ovalbumin
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th1 Cells / pathology

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Immunosuppressive Agents
  • Berberine
  • Ovalbumin