Inhibitory effect of α-amyrin acetate isolated from Fraxinus rhynchophylla on Th17 polarization.

BACKGROUND

T helper 17 (Th17) cells, which are differentiated from CD4 T cells, drive inflammation, leading to autoimmune diseases such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Therefore, inhibiting Th17 polarization could be a therapeutic target for inflammatory diseases.

PURPOSE

We investigated the inhibitory effect of Fraxinus rhynchophylla (Oleaceae) on Th17 differentiation and found its active component.

STUDY DESIGN

The activity of F. rhynchophylla and its active constituent was verified using CD4 cells extracted from C57BL/6 mice.

METHODS

Micro-environment for Th17 polarization was provided to CD4 cells and the effect of treatment with samples was measured by enzyme linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and Western blot.

RESULTS

The extract of F. rhynchophylla Hance and its chemical constituent, α-amyrin acetate, which was isolated via bioassay-guided isolation, significantly inhibited Th17 polarization as revealed when interleukin (IL)-17, a characteristic cytokine produced by Th17 cells, was measured. Furthermore, the inhibitory effect of α-amyrin acetate was compared to the amyrin derivatives, α-amyrin and β-amyrin. All displayed a suppressive effect on Th17 polarization and all reduced the expression of single transducer and activator of transcription 3 (STAT3) and retinoic acid receptor-related orphan receptor γt (RORγt), which are crucial transcription factors regulating Th17 differentiation. α-Amyrin acetate, however, exhibited the most prominent effects, which indicates that the functional group, acetate, might strengthen the inhibitory effect on Th17 differentiation.

CONCLUSION

Taken together, these results suggest that the extract of F. rhynchophylla and its active constituent, α-amyrin acetate, could be applied as a potential therapeutic agent for autoimmune disorders such as rheumatoid arthritis.