An eco-friendly enantioselective access to (R)-Naringenin as inhibitor of proinflammatory cytokine release.

(R/S)-Naringenin is a flavanone, well-known for its beneficial health-related properties, such as anti-inflammatory activity. The preparative enantioselective chromatographic resolution of commercial (R/S)-Naringenin was performed on Chiralpak® AD-H column (500 x 50 mm I.D., dp = 20 μm) using methanol as eluent. The developed method is in accordance with the principles of green chemistry, since the environmental impact was lowered through the recycle of eluent. In this way, g-amounts of each enantiomer were recovered with high purity (chemical purity > 99%, enantiomeric excess > 94%). The racemic and enantiomeric Naringenin were subjected to an exhaustive in vitro investigation of anti-inflammatory activity, aimed at evaluating the relevance of chirality. The assay on cultured human peripheral blood mononuclear cells activated by Phytohemagglutinin A revealed that (R)-Naringenin is the most effective in inhibiting the T-cell proliferation, showed to be still active at lowest concentration. Moreover, (R)-Naringenin significantly reduced pro-inflammatory cytokines levels such as TNF-α and, with less potency, IL-6. These results evidenced the anti-inflammatory potential of Naringenin and the highest capacity of (R)-Naringenin to inhibit both in vitro PBMC proliferation and cytokines secretion at non toxic doses. Thus, (R)-Naringenin is a promising candidate for in vivo investigation.