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

Abstract

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.

• Authors: Dae-Gun Seo, Sunggun Kim, Da Kyung Lee, Na Yeon Kim, Jae-Sun Lee, Kwang Woo Hwang, So-Young Park
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 63 Pg. 153056 (Oct 2019) ISSN: 1618-095X [Electronic] Germany
• PMID: 31398661 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier GmbH. All rights reserved.

Chemical References

• Il17a protein, mouse
• Interleukin-17
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Plant Extracts
• Rorc protein, mouse
• STAT3 Transcription Factor
• Stat3 protein, rat
• Oleanolic Acid
• beta-amyrin acetate

Topics

• Animals
• CD4-Positive T-Lymphocytes (drug effects)
• Cell Differentiation (drug effects)
• Cell Polarity (drug effects, immunology)
• Fraxinus (chemistry)
• Interleukin-17 (genetics, metabolism)
• Male
• Mice, Inbred C57BL
• Nuclear Receptor Subfamily 1, Group F, Member 3 (genetics, metabolism)
• Oleanolic Acid (analogs & derivatives, isolation & purification, pharmacology)
• Plant Extracts (chemistry, pharmacology)
• STAT3 Transcription Factor (genetics, metabolism)
• Th17 Cells (drug effects)