New Monoterpene Acid and Gallic Acid Glucose Esters with Anti-Inflammatory Activity from Blue Gum ( Eucalyptus globulus ) Leaves.

Blue gum ( Eucalyptus globulus ) is a widely used botanical in the cosmeceutical and food industries. Although blue gum leaves are known for abundant essential oils, their nonvolatile phytochemical constituents and bioactivities remain unclear. Herein, a phytochemical investigation of blue gum leaves led to the identification of eight new monoterpene acid and gallic acid glucose esters ( 1-4 and 14-17 ; glubosides A-H, respectively) and 12 known analogues ( 5-13 and 18-20 ). Their structures were determined based on extensive spectroscopic data analysis, chemical degradation, and chiral separation. Oleuropeic acid conjugated glucose esters ( 1-13 , 15 , 16 , 18 , and 20 ) are reported as epimeric mixtures. Compounds 7 , 12 , 14 , 19 , and 20 (at 30 μM) inhibited nitrite release in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Compounds 7 and 14 (at 3-30 μM) also down-regulated proinflammatory biomarkers, including cytokines (TNF-α, IL-6, and IL-1β), protein expression (iNOS and COX-2), and transcription factor nuclear translocation (NF-κB) in LPS-stimulated RAW264.7 cells. This work highlights the anti-inflammatory potential of phytochemicals from blue gum leaves, which supports their further development as cosmeceutical and/or nutraceutical products.