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 mu M) inhibited nitrite release in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Compounds 7 and 14 (at 3-30 mu M) also down-regulated proinflammatory biomarkers, including cytokines (TNF-alpha, IL-6, and IL-1 beta), protein expression (iNOS and COX-2), and transcription factor nuclear translocation (NF-kappa B) 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.