Proanthocyanidin-rich fractions prepared from blueberry leaf hot-water extracts inhibits interleukin-1β production in RAW264 cells and induces autophagy.

Blueberry leaves (Vaccinium virgatum Aiton), cultivated in Miyazaki Prefecture, Japan, represent a promising natural health-promoting resource. This study investigated the anti-inflammatory effects of blueberry leaf extract (BLEx) using lipopolysaccharide-stimulated RAW264 macrophage cells. BLEx (up to 100 μg/mL) significantly suppressed nitric oxide production and reduced both the secretion and mRNA expression of interleukin (IL)-1β and IL-6, while showing no significant effect on tumor necrosis factor-α, indicating selective anti-inflammatory activity. Highly polymerized proanthocyanidins, one of the major components of BLEx, contributed to the suppression of IL-1β production. BLEx treatment also induced morphological changes, including intracellular vacuole formation, suggesting the involvement of autophagy. Consistently, the expression of autophagy-related factors increased in a concentration-dependent manner, and inhibition of autophagy attenuated the suppressive effect of BLEx on IL-1β. Overall, BLEx exerts anti-inflammatory effects partly via autophagy activation and may be useful for preventing IL-1β-related inflammatory disorders.