Introduction During the past few decades, the number of patients suffering from immune disorders such as allergy, autoimmune diseases, and relapsed infections has shown a steady increase worldwide [1–3]. An urgent need exists for efficient prevention and/or treat- ment methods as evidenced by the many attempts to develop a novel therapy for immune diseases. Ye et al. [4] pointed out that improved strategies and targets for immunomodulation of aller- gic diseases should consider aspects such as fewer side effects, antigen-specific modulation for long-term effects, and non-injec- tion routes. Mucosal immunotherapy is therefore an ideal choice based on these considerations. The health-promoting functions of some phytochemical constituents are receiving increasing at- tention with many studies revealing that their daily intake contrib- utes to reducing the number of patients with diseases such as allergy, arteriosclerosis, and cancer [5–7]. Some of the immune- modulating effects might be achieved through enhancement of Authors Shiho Murakami 1 , Yutaka Miura 1 , Makoto Hattori 1 , Hiroshi Matsuda 2 , Christiaan J. Malherbe 3 , Christo J. F. Muller 4 , Elizabeth Joubert 3,5 , Tadashi Yoshida 1 Affiliations 1 Department of Applied Biological Science, Tokyo Univer- sity of Agriculture and Technology, Tokyo, Japan 2 Division of Animal Life Science, Tokyo University of Agri- culture and Technology, Tokyo, Japan 3 Plant Bioactives Group, Post-Harvest and Agro-Processing Technologies Division, Agricultural Research Council, Stellenbosch, South Africa 4 Biomedical Research and Innovation Platform, South Afri- can Medical Research Council, Tygerberg, South Africa 5 Department of Food Science, Stellenbosch University, Stellenbosch, South Africa Key words Cyclopia Vent., cytokines, Foxp3 + , T cell proliferation, Th1, Th2, Th17 received June 2, 2017 revised October 3, 2017 accepted October 6, 2017 Bibliography DOI https://doi.org/10.1055/s-0043-121270 Published online November 2, 2017 | Planta Med 2018; 84: 311–319 © Georg Thieme Verlag KG Stuttgart · New York | ISSN 0032‑0943 Correspondence Dr. Tadashi Yoshida Department of Applied Biological Science, Tokyo University of Agriculture and Technology 3-5-8 Saiwai-cho, Fuchu City, Tokyo 183-8509, Japan Phone: + 81 4 23 67 57 11, Fax: + 81 4 23 67 57 11 tyoshi@cc.tuat.ac.jp ABSTRACT Cyclopia genistoides, one of the traditional South African me- dicinal plants, and other species of the same genus offer note- worthy phenolic profiles, in particular high levels of the anti- allergic xanthone mangiferin. Hot water and 40% ethanol- water (v/v) extracts, prepared from C. genistoides, Cyclopia subternata, and Cyclopia maculata, were tested for immune- regulating activity in vitro using murine splenocytes and mes- enteric lymph node cells. The 40% ethanol-water extracts of C. genistoides and C. subternata significantly enhanced pro- duction of several types of cytokines, including IL-4, IL-17, and IFN-γ, by antigen-stimulated splenocytes. A concentra- tion-dependent response was observed, noticeably for IFN-γ production. The activity of the extracts did not correlate with the content of any of the major phenolic compounds, in- dicative that other extract constituents also play a role in immunomodulation. Additionally, the increased ratio of CD4 + CD25 + Foxp3 + Treg cells to total CD4 + cells indicated in- duction of Foxp3 + cells when mesenteric lymph node cells were cultured in the presence of these two extracts. This study is the first reporting immunostimulatory activity for Cy- clopia, which are widely consumed as the herbal tea known as honeybush, underpinning further investigations into the po- tential use of its extracts as adjuvants for mucosal immuno- therapy. Cyclopia Extracts Enhance Th1-, Th2-, and Th17-type T Cell Responses and Induce Foxp3 + Cells in Murine Cell Culture Original Paper 311 Murakami S et al. Cyclopia Extracts Enhance … Planta Med 2018; 84: 311–319 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.