Abstract
Viola tricolor is a medicinal plant with documented application as an anti-inflammatory herb. The
standard of care for the treatment of inflammatory bowel disease is
immunosuppressive therapeutics or biologics, which often have undesired effects. We
explored V. tricolor herbal preparations that are rich in an emerging class of phytochemicals with
drug-like properties, so-called cyclotides. As an alternative to existing inflammatory
bowel disease medications, cyclotides have immunomodulatory properties, and their
intrinsic stability
allows for application in the gastrointestinal tract, for instance, via oral administration.
We optimized the isolation procedure to improve the yield of cyclotides and compared
the cellular
effects of violet-derived organic solvent-extracts, aqueous preparations, and an isolated
cyclotide from this plant on primary human T lymphocytes and macrophages, i.e., cells
that are
crucial for the initiation and progression of inflammatory bowel disease. The hot
water herbal decoctions have a stronger immunosuppressive activity towards proliferation,
interferon-γ, and interleukin-21 secretion of primary human T cells than a DCM/MeOH cyclotide-enriched
extract, and the isolated cyclotide kalata S appears as one of the active
components responsible for the observed effects. This effect was increased by a longer
boiling duration. In contrast, the DCM/MeOH cyclotide-enriched extract was more effective
in reducing
the levels of cytokines interleukin-6, interleukin-12, interleukin-23, tumor necrosis
factor-α, and C – X-C motif chemokine ligand 10, secreted by human monocyte-derived macrophages.
Defined cyclotide preparations of V. tricolor have promising pharmacological effects in modulating immune cell responses at the
cytokine levels. This is important towards
understanding the role of cyclotide-containing herbal drug preparations for future
applications in immune disorders, such as inflammatory bowel disease.
Key words
violet - cyclotide - macrophage - T cell - kalata S -
Viola tricolor
- Violaceae
