Neutrophil Immunomodulatory Activity of (-)-Borneol, a Major Component of Essential Oils Extracted from Grindelia squarrosa .

Grindelia squarrosa (Pursh) Dunal is used in traditional medicine for treating various diseases; however, little is known about the immunomodulatory activity of essential oils from this plant. Thus, we isolated essential oils from the flowers (GEO Fl ) and leaves (GEO Lv ) of G. squarrosa and evaluated the chemical composition and innate immunomodulatory activity of these essential oils. Compositional analysis of these essential oils revealed that the main components were α-pinene (24.7 and 23.2% in GEO Fl and GEO Lv , respectively), limonene (10.0 and 14.7%), borneol (23.4 and 16.6%), p -cymen-8-ol (6.1 and 5.8%), β-pinene (4.0 and 3.8%), bornyl acetate (3.0 and 5.1%), trans -pinocarveol (4.2 and 3.7%), spathulenol (3.0 and 2.0%), myrtenol (2.5 and 1.7%), and terpinolene (1.7 and 2.0%). Enantiomer analysis showed that α-pinene, β-pinene, and borneol were present primarily as (-)-enantiomers (100% enantiomeric excess (ee) for (-)-α-pinene and (-)-borneol in both GEO Fl and GEO Lv ; 82 and 78% ee for (-)-β-pinene in GEO Fl and GEO Lv ), while limonene was present primarily as the (+)-enantiomer (94 and 96 ee in GEO Fl and GEO Lv ). Grindelia essential oils activated human neutrophils, resulting in increased [Ca 2+ ] i (EC 50 = 22.3 µg/mL for GEO Fl and 19.4 µg/mL for GEO Lv ). In addition, one of the major enantiomeric components, (-)-borneol, activated human neutrophil [Ca 2+ ] i (EC 50 = 28.7 ± 2.6), whereas (+)-borneol was inactive. Since these treatments activated neutrophils, we also evaluated if they were able to down-regulate neutrophil responses to subsequent agonist activation and found that treatment with Grindelia essential oils inhibited activation of these cells by the N -formyl peptide receptor 1 (FPR1) agonist f MLF and the FPR2 agonist WKYMVM. Likewise, (-)-borneol inhibited FPR-agonist-induced Ca 2+ influx in neutrophils. Grindelia leaf and flower essential oils, as well as (-)-borneol, also inhibited f MLF-induced chemotaxis of human neutrophils (IC 50 = 4.1 ± 0.8 µg/mL, 5.0 ± 1.6 µg/mL, and 5.8 ± 1.4 µM, respectively). Thus, we identified (-)-borneol as a novel modulator of human neutrophil function.