Brazilian green propolis and its constituent, Artepillin C inhibits allogeneic activated human CD4 T cells expansion and activation

• Published in: Journal of ethnopharmacology Vol. 138; no. 2; pp. 463 - 471
• Main Authors: Cheung, Ka-Wai, Sze, Daniel Man-Yuen, Chan, Wing Keung, Deng, Rui-Xia, Tu, Wenwei, Chan, Godfrey Chi-Fung
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 18.11.2011; Elsevier
• Subjects: apoptosis; Artepillin C; Biological and medical sciences; Brazilian green propolis; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Cell Division - drug effects; Cell Line; cell proliferation; Chromatography, High Pressure Liquid; cytokines; cytotoxicity; Enzyme-Linked Immunosorbent Assay; General pharmacology; hosts; human cell lines; Humans; interferon-gamma; interleukins; Lymphocyte Activation - drug effects; mechanism of action; Medical sciences; Mixed leukocyte reaction; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phenylpropionates - pharmacology; Propolis; Propolis - chemistry; Propolis - pharmacology; T cell; T cell activation; T-lymphocytes; traditional medicine; South America; Brazil; America; IL; T cell activation; Propolis; T cell; Treg; CFSE; GVHD; FK506; Mixed leukocyte reaction; PBMC; Brazilian green propolis; Art-C; CsA; IFN-γ; APC; TNF-α; Artepillin C; PBrazil; PBL; Foxp3; Allo-HSCT; Human; Leukocyte; Pharmacognosy; Animal origin; Allogeneic system; Medicinal plant; Folk medicine; Cinnamic acid derivatives; T-Lymphocyte; Plant origin
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2011.09.031

Propolis has long been used as a popular folk medicine by various ethnic groups due to its wide spectrum of alleged biological and pharmaceutical properties including anti-microbial, anti-cancer and anti-inflammatory functions. All these can be linked to the modulation of immune function. Therefore, it will be relevant for us to find out whether there is any novel compound that can account for such action and the mechanism involved. We investigated the immune modulating effect of Brazilian green propolis (PBrazil) and its constituent Artepillin C (Art-C) by using mixed leukocytes reaction. The cytotoxic effect of Art-C on non-tumorigenic human liver cell line miHA and non-tumorigenic human kidney cell line HK-2 as well as human peripheral blood mononuclear cells (PBMCs) were measured by XTT cell proliferation assay. The effect of PBrazil and Art-C on T cell proliferation and activation were determined by using carboxyfluorescein succinimidyl ester (CFSE) and by CD25 expression, respectively. Cytokines including tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), interleukins such as IL-2, IL-17 were measured by intracellular cytokine staining and IL-10 was measured by ELISA. The effect of PBrazil and Art-C on regulatory T cells (Treg) induction was determined by the Foxp3 expression. The apoptotic effect of these compounds on CFSE labeled alloreactive T cells was measured by using Annexin V. Using mixed leukocytes reaction we demonstrated for the first time that both Art-C and PBrazil significantly inhibited the alloreactive CD4 T cell proliferation, activation, and suppressed the expressions of IL-2, IFN-γ and IL-17 in these alloreactive CD4 T cells. The inhibitions of Art-C and PBrazil on CD4 T cells were not due to direct cytotoxic effect on PBMC or inducing regulatory T cells differentiation. Both Art-C and PBrazil were found to selectively induce apoptosis in proliferating T cells. The anti-proliferative effect of Art-C and PBrazil were reversible and were also applied to the activated T cells. In conclusion, our results indicated that Art-C and PBrazil can suppress alloreactive CD4 T cell responses in vitro, suggesting that Art-C could be used as a potential immunosuppressant, either solely or as adjunct agent in treating graft versus host disease.