Volume 151, Issue 1, 10 January 2014, Pages 299–306
Immunosuppressive activity of an aqueous Viola tricolor herbal extract
Abstract
Ethnopharmacological relevance
Heartsease (Viola tricolor L.), a member of the Violaceae
family, has a long history as a medicinal plant and has been documented
in the Pharmacopoeia of Europe. Due to its anti-inflammatory properties
it is regarded as a traditional remedy against skin diseases, for
example for the treatment of scabs, itching, ulcers, eczema or
psoriasis, and it is also used in the treatment of inflammation of the
lungs and chest such as bronchitis or asthma. Because T-cells play an
important role in the pathological process of inflammatory diseases we
investigated the effect of an aqueous Viola extract on lymphocyte functions and explored the ‘active’ principle of the extract using bioactivity-guided fractionation.
Material and Methods
An aqueous Viola extract was prepared by C18
solid-phase extraction. Effects on proliferation of activated
lymphocytes (using the cell membrane permeable fluorescein dye CFSE),
apoptosis and necrosis (using annexin V and propidium iodide staining),
interleukin-2 (IL-2) receptor expression (using fluorochrome-conjugated
antibodies) and IL-2 cytokine secretion (using an ELISA-based bead array
system) were measured by flow cytometry. Influence on lymphocyte
polyfunctionality was characterized by Viola extract-induced
production of IFN-γ and TNF-α, as well as its influence on lymphocyte
degranulation activity. Fractionation and phytochemical analysis of the
extract were performed by RP-HPLC and mass spectrometry.
Results
The aqueous Viola
extract inhibited proliferation of activated lymphocytes by reducing
IL-2 cytokine secretion without affecting IL-2 receptor expression.
Similarly, effector functions were affected as indicated by the
reduction of IFN-γ and TNF-α production; degranulation capacity of
activated lymphocytes remained unaffected. Bioassay-guided fractionation
and phytochemical analysis of the extract led to identification of
circular plant peptides, so called cyclotides, as bioactive components.
Conclusion
An aqueous Viola
extract contains bioactive cyclotides, which inhibit proliferation of
activated lymphocytes in an IL-2 dependent manner. The findings provide a
rationale for use of herbal Viola preparations in the therapy
of disorders related to an overactive immune system. However, further
studies to evaluate its clinical potency and potential risks have to be
performed.
Graphical abstract
Keywords
- Violaceae;
- Viola tricolor L.;
- Immunosuppression;
- Cyclotides;
- Psoriasis;
- Anthroposophical medicine;
- Phytotherapy
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