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

• C.oil inhibits cytokine production by targeting the TLR4–IRAK1–ROS–MAPK–NFκB axis.
• C.oil inhibits LPS induced inflammation by blocking recruitment of MyD88 to TLR4.
• C.oil prevents LPS induced mice and human whole blood inflammation.
• C.oil ameliorates LPS induced endothelial dysfunction and inflammation in mice.
• C.oil attenuates oxidative stress induced deleterious effects in mice.

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.