Abstract
BACKGROUND: Diabetes Mellitus (DM) poses a serious health problem worldwide and several inflammatory mediators are involved in the pathogenesis of this disease. Honey composed of various constituents which have been proven to have immunomodulatory and anti-inflammatory properties. The aim of this study is to investigate the in vitro and in vivo effects of Ziziphus honey and its isolated crude proteins in modulation of immune system and inflammation involved in the pathogenesis of diabetes. METHODOLOGY: The proteins from Ziziphus honey were isolated by ammonium sulfate precipitation and estimated by Bradford method. In vitro anti-inflammatory activities were evaluated by inhibition of reactive oxygen species (ROS) from phagocytes via chemiluminescence immunoassay and nitric oxide (NO) by Griess method. Cytotoxicity was evaluated by MTT Assay. The comparative effect of oral and IP routes of honey and isolated proteins was observed in streptozotocin (STZ) induced diabetic male Wistar rats. qRT-PCR technique was utilized for gene expression studies. RESULTS: The honey proteins suppressed phagocyte oxidative burst and nitric oxide (NO) at significantly lower concentrations as compared to crude honey. The isolated proteins showed promising anti-inflammatory and hypoglycemic effects along with maintenance of body weight of rodents via both oral and IP routes, with significant down-regulation of inflammatory markers TNF-α, IL-1β, IFN-γ, iNOS, caspase 1, Calgranulin A (S100A8) and NF-κB expression in diabetic rats. CONCLUSION: The isolated honey proteins showed better immunomodulatory and therapeutic potential at significantly lower doses as compared to crude honey.