Determination of suppressive effect on human T-cell activation by hispidulin, nepetin, and vanillic acid

Abstract

Background: Hispidulin, nepetin, and vanillic acid are phenolic compounds potentially possessing immunosuppressive property, however, no information on their pharmacological effect and cytotoxicity has been investigated on human T lymphocytes.

Materials and methods: Human peripheral blood mononuclear cells were stimulated with anti-CD3/28 coated beads and treated with individual compound at different concentrations (50–200 µM). Inhibition of early cell activation and induction of apoptosis were analyzed by flow cytometric technique.

Results: At 200 µM, frequencies of CD25 and CD69 in CD4⁺ and CD8⁺ T lymphocytes were markedly decreased by hispidulin and nepetin. When lowering to 100 and 50 µM, hispidulin had no effect on the expression of CD69 in CD4⁺ T cells, whereas nepetin selectively suppressed CD25 and CD69 expressions in CD8⁺ T cells at 100 µM and only inhibited CD69 in CD8⁺ T cells at 50 µM. For vanillic acid, no inhibitory effect was observed while cell activation was significantly increased for all treated concentrations. None of these compounds disturbed levels of total apoptotic cells in CD4⁺ and CD8⁺ populations.

Conclusions: Hispidulin and nepetin, therefore, exhibit dose-dependent inhibitory activity of early T-cell activation without inducing cell death, considering feasible immunosuppressants for inflammation-related diseases. However, vanillic acid has no effect on immunosuppression but shows more potential on immunostimulation.

Highlights

• Immunosuppressive effects of hispidulin and nepetin on human T cells were studied.

• Dose-dependent activity for T-cell suppression was found in hispidulin and nepetin.

• Vanillic acid showed immunostimulating potential rather than immunosuppression.

• All compounds did not induce cell death.

Keywords:

• Hispidulin
• nepetin
• vanillic acid
• immunosuppression
• T-cell activation

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was supported by The Thailand Research Fund [grant number MRG5980259]. PT and NO are supported by Chalermphrakiat Grant from Faculty of Medicine Siriraj Hospital, Mahidol University. The authors gratefully thank all volunteers donating blood for this study.