T cell inhibition by pogostone from Pogostemon cablin (Blanco) Benth: In vitro and in vivo immunosuppressive analysis

Abstract

Various plant-derived compounds exhibit immunosuppressive activity in pre-clinical investigations, suggesting that they may serve as natural alternatives for the prevention of inflammatory disorders and autoimmune diseases. The aim of the current study was to explore the immunosuppressive potential of pogostone (PO) derived from Pogostemon cablin (Blanco) Benth. Carboxyfluorescein diacetate succinimidyl ester-labeled cell tracking demonstrated that PO (20–80 µM) inhibited Concanavalin A (ConA)-stimulated lymphocyte proliferation, which was mediated by G0/G1 phase arrest and accompanied by significant decreases in the expression of CD69 (early-stage activation marker) and CD25 (mid-stage activation marker) in T cells, as indicated by flow cytometry analysis. Furthermore, the proliferation blocking ability of PO (5–80 µM) was not associated with cytotoxicity in normal lymphocytes or apoptosis in ConA-stimulated lymphocytes. The inflammatory cytokine profile determination using a cytometric beads assay revealed that PO inhibited release of anti-inflammatory interleukin (IL)-10 and pro-inflammatory IL-6 from the stimulated lymphocytes. Furthermore, PO (10, 20 or 40 mg/kg) ameliorated the T-cell mediated delayed type hypersensitivity response in Balb/c mice by reducing leukocyte infiltration and tissue edema, providing a further validation of the direct immunosuppressive activity of PO. Together, the present data suggest that PO would suppress T cell response via a direct non-cytotoxic inactivation at the early stage, accompanied by regulation of the inflammatory cytokine profile, which highlights clinical implications for treatment of immune-based disorders.