Anti-allergic Activity of Sesquiterpenes from the Rhizomes of Cyperus rotundus

From the 70% ethanol extract of the rhizomes of Cyperus rotundus (CRE), several major constituents including the sesquiterpene derivatives (valencene, nootkatone, and caryophyllene alpha-oxide), monoterpenes (beta-pinene, 1,8-cineole, and limonene) and 4-cymene were isolated and examined for their anti-allergic activity in vitro and in vivo. In rat basophilic leukemia (RBL)-1 cells, the sesquiterpenes strongly inhibited 5-lipoxygenase-catalyzed leukotrienes production. In addition, they inhibited beta-hexosaminidase release by antigen-stimulated RBL-2H3 cells, with valencene having the highest inhibitory effect. CRE inhibited leukotrienes production and beta-hexosaminidase release at 300 mu g/mL. It was also found that the most active sesquiterpene (valencene) and CRE inhibited beta-hexosaminidase degranulation by inhibiting the initial activation reaction, Lyn phosphorylation, in IgE-stimulated RBL-2H3 cells. Moreover, CRE, valencene and nootkatone significantly inhibited the delayed-type hypersensitivity reaction in mice when administered orally at 50 - 300 mg/kg. In conclusion, C. rotundus and its constituents, valencene, nootkatone, and caryophyllene alpha-oxide, exert anti-allergic activity in vitro and in vivo. These sesquiterpenes, but not monoterpenes, certainly contribute to the anti-allergic activity of the rhizomes of C. rotundus.