Modulatory potentials of zerumbone isolated from ginger (Zingiber zerumbet) on eicosanoids: evidence from LPS induced peripheral blood leukocytes

Several bioactive molecules from plant origin have been studied for their anti-inflammatory properties. In this study, we deciphered the anti-eicosanoid properties of zerumbone (sesquiterpene) isolated from ginger ( Zingiber zerumbet ) in LPS induced peripheral blood leukocytes from rats. Molecular interaction between zerumbone (Z) and eicosanoid metabolizing enzymes (COX-2, 5-LOX, FLAP, and LTA 4 -hydrolase) and receptors (EP-4, BLT-1, and ICAM-1) along with NOS-2 were assessed using Auto-Dock 4.2 docking software. Further, the rat peripheral blood leukocytes were isolated and treated with zerumbone (5μM) and activated using bacterial lipopolysaccharide (10nM). Oxidative stress (OS) markers, reactive oxygen species, antioxidant enzymes, COX-2, 5-LOX, BLT-1, EP-4 were assessed along with the activity of COX-2. Zerumbone showed a higher binding affinity with mPGES-1, NOS-2, FLAP, COX-2, LTA-4-hydrolase, and BLT-1 mediators of the eicosanoid pathway. Further, zerumbone significantly (p<0.05) inhibited COX-2, 5-LOX, NOS-2, EP-4, BLT-1, and ICAM-1 expression in LPS induced peripheral blood leukocytes from rats. Zerumbone positively modulates critical enzymes and receptors of eicosanoids in leukocytes activated with lipopolysaccharides. Thus, zerumbone offers a promising therapeutic strategy in the management of inflammation.