Turmerone enriched standardized Curcuma longa extract alleviates LPS induced inflammation and cytokine production by regulating TLR4-IRAK1-ROS-MAPK-NFκB axis

In the present study turmerone enriched curcuma oil (C.oil) obtained from Curcuma longa L. was evaluated in lipopolysaccharide (LPS) induced inflammation in THP-1 human monocytes, J774.2 murine macrophages and Swiss mice. THP-1, J774.2 and mice or human whole blood pre-treated with C.oil (1-30 μg/ml; 14 h) and stimulated with LPS (50 ng/ml-1 μg/ml) showed significant reduction in TNF-α, IL-1β and IL-6 production compared to respective control. C.oil significantly attenuated LPS induced TLR4-MyD88 interaction and IRAK1, MAPK, ROS and NFκB pathway activation in a dose dependent manner. Plasma TNF-α, IL-1β, IL-6, nitrite, aortic iNOS expression and p38 MAPK activation, endothelial dysfunction and oxidative stress markers namely lipid hydroperoxide, 8-hydroxydeoxyguanosine, 8-isoprostane and protein carbonyl were also attenuated in C.oil (100, 300 mg/kg; 10 days p.o.) pre-treated and LPS (10 mg/kg) challenged Swiss mice when compared to LPS alone. The present study gives a mechanistic insight into the nutraceutical potential of C.oil for preventing endotoxin induced inflammatory sepsis.