Background: Systemic acute inflammation is the hallmark of sepsis and is associated with multiple organ dysfunction. Objective: This study investigated the potential of Stingless Bee Honey (SBH) to suppress lipopolysaccharide (LPS)-induced systemic acute inflammation in rats and to reveal the probable mechanism of action. Methods: Rats received 4.6 and 9.2 g/kg SBH for 7 days followed by a single injection of LPS after which blood samples were taken 6h later. Results: LPS induced liver, kidney, heart, and lung injury, were manifested by increased serum transaminases, alkaline phosphatase, creatine kinase, creatinine, and urea, along with multiple histological alterations, particularly leukocyte infiltration. Pro-inflammatory cytokines were elevated in the serum, and NF-κB p65, p38 MAPK, and HMGB-1 were significantly increased in different tissues of LPS-challenged rats. SBH prevented tissue injury, ameliorated pro-inflammatory cytokines, and suppressed NF-κB p65, p38 MAPK, and HMGB-1 in rats that had received LPS. In addition, SBH diminished reactive oxygen species (ROS) production, lipid peroxidation, and oxidative DNA damage, and enhanced glutathione and Nrf2 in LPS-treated rats. Conclusion: SBH prevents systemic acute inflammation by suppressing NF-κB, p38 MAPK, HMGB-1, oxidative stress, and tissue injury in rats. Thus, SBH may represent an effective anti-inflammatory nutraceutical, pending further mechanistic studies.
