Novel kojic acid derivatives with anti-inflammatory effects from Aspergillus versicolor

Abstract

Two novel kojic acid derivatives, kojicones A and B (1 and 2), along with the precursors kojic acid (3) and (2R,4R)-4-hydroxy-5-methoxy-2,4-dimethyl-2- [(2R)-2-methylbutyryloxy]-5-cyclohexen-1,3-dione (4), were isolated from a fungal strain Aspergillus versicolor. Their structures and absolute configurations were accurately confirmed by HRESIMS data, NMR analysis, and electronic circular dichroism (ECD) calculations. Kojicones A and B were the first examples of kojic acid adducts with cyclohexen-1,3-dione possessing unprecedented tricycle skeletons. Compounds 1–3 were found to have inhibition on the NO production of murine RAW 264.7 cells. They can also reduce the mRNA expression of four cytokines (IL-6, IL-1β, TNF-α, and iNOS) and promote the expression of IL-4 at 20 μM. Moreover, kojic acid (3) could treat the DSS (dextran sulfate sodium)-induced colitis on mice with the effectiveness similar to that of the positive control. The results suggested that kojic acid and its derivatives could be a promising anti-inflammatory source for the medicinal and cosmetic industry.