Protective effects of Manuka honey on LPS-treated RAW 264.7 macrophages. Part 2: Control of oxidative stress induced damage, increase of antioxidant enzyme activities and attenuation of inflammation.

The redox-system is altered by oxidative stress that is initiated by oxidative agents such as lipopolysaccharides (LPS) and reactive oxygen species (ROS), which are strongly involved in chronic inflammation. Even if Manuka honey (MH) is a good source of polyphenol rich antioxidants, its antioxidant and anti-inflammatory effects are still elusive. The aim of the present work was to explore the protective effects of MH against E.coli LPS stimulated oxidative stress and inflammatory condition and the underlying mechanisms on murine RAW 264.7 macrophages. Pre-treatment with MH markedly inhibited LPS induced ROS and nitrite accumulation and increased the protection against cellular biomolecules such as lipids, proteins, and DNA. Stimulation by LPS suppressed both antioxidant enzyme activities and expressions, and Keap1-Nrf2 signaling pathway which was significantly (p < 0.05) increased in the presence of MH. The pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6, and other inflammatory mediators (iNOS) were enhanced after LPS treatment, whereas MH suppressed the expression of these inflammatory markers. Moreover, MH also inhibited the expression of TLR4/NF-кB via IкB phosphorylation in LPS-stressed RAW 264.7 macrophages. In conclusion, MH acted as a natural agent for preventing oxidative and inflammatory-related diseases.