Epicatechin oligomers longer than trimers have anti-cancer activities, but not the catechin counterparts.

Since procyanidins (oligomeric catechin or epicatechin) were reported to exhibit health benefits, much attention has been paid to the synthesis of these compounds, especially those that are longer than trimers. In the present study, syntheses of cinnamtannin A3 (epicatechin pentamer), A4 (epicatechin hexamer), catechin tetramer, pentamer, arecatannin A2 (epicatechin-epicatechin-epicatechin-catechin) and A3 (epicatechin-epicatechin-epicatechin-epicatechin-catechin) were achieved. The key reaction was a Lewis acid mediated equimolar condensation. The antitumor effects of these synthesized compounds against a human prostate cancer cell line (PC-3) were investigated. Among the tested compounds, cinnamtannin A3, A4 and arecatannin A3, which possess epicatechin oligomers longer than tetramers as the basic scaffold, showed significant activities for suppression of cell growth, invasion and FABP5 (fatty acid-binding protein 5) gene expression. Effects on cell cycle distribution showed that cell cycle arrest in the G2 phase was induced. Furthermore, these epicatechin oligomers suppressed significantly the expression of the cancer-promoting gene, FABP5, which is related to cell proliferation and metastasis in various cancer cells. Interestingly, the suppressive activities were associated with the degree of oligomerization of epicatechin. Thus, synthetic studies clearly demonstrate that epicatechin oligomers longer than trimers have significant anti-tumorigenic activities, but not the catechin counterparts.

Procyanidin B2 gallates inhibit IFN-γ and IL-17 production in T cells by suppressing T-bet and RORγt expression.

Procyanidins are widely found in plants and have anti-inflammatory activities. Procyanidin B2 (PCB2) inhibits production of proinflammatory cytokines in macrophages. However, there has been no study that has attempted to determine the effects of PCB2 gallates on T cell functions. In the present study, murine splenocytes were isolated and treated with PCB2 or PCB2 gallates in the presence of an anti-CD3 monoclonal antibody (mAb). PCB2 gallates, but not PCB2, inhibited proliferation and T cell activation of splenocytes after stimulation with the anti-CD3 mAb. In addition, PCB2 gallates, particularly 3,3″-di-O-gallate (3,3″-di-OG), significantly inhibited production of interferon (IFN)-γ, interleukin (IL)-12p40, and IL-17 in splenocytes, but did not suppress IL-10 production. Intracellular staining revealed that the expression of IFN-γ and IL-17 in both CD4+ and CD8+ T cells was obviously decreased by PCB2 3,3″-di-OG compared with PCB2, PCB2 3-OG, and PCB2 3″-OG. Treatment of isolated CD4+ and CD8+ T cells with procyanidins in the presence of the anti-CD3 mAb led to significant inhibition of IFN-γ production by PCB2 3,3″-di-OG in both cell types. Furthermore, PCB2 3,3″-di-OG suppressed the expression of transcription factors T-bet and RORγt that regulate IFN-γ and IL-17, respectively. In conclusion, we revealed a new mechanism through which PCB2 gallates inhibit IFN-γ and IL-17 production in T cells by down-regulation of T-bet and RORγt expression. Our results suggest that PCB2 gallates have a potential role in Th1/Th17-mediated diseases such as inflammatory and autoimmune diseases.