Protective effect of isoliquiritigenin against cerebral injury in septic mice via attenuation of NF-κB.
Inflammopharmacology. 2019 Aug ;27(4):809-816. Epub 2018 Jun 26. PMID: 29943151
BACKGROUND: The study was conducted to scrutinize the outcome of isoliquiritigenin (ISL) against cerebral injury in septic mice.
METHODS: The sepsis was introduced using cecal ligation and puncture (CLP) method in experimental mice. The effect of ISL was quantified using the content of brain water and blood brain barrier (BBB) permeability. The effect on the levels of myeloperoxidase (MPO), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in brain homogenates was also determined. The effect of ISL on the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in serum was also estimated. The levels of various inflammatory biomarkers (COX-2 and PGE2) were also studied. The expression of NF-κB signalling cascade and inducible nitric oxide synthase (iNOS) was estimated by Western blot.
RESULTS: Compared with CLP group, the brain water content was found to be reduced significantly together with the enhanced BBB integrity in ISL treated group. The level of MDA was reduced together with enhanced level of SOD and GSH in the ISL treated group. The levels of TNF-α, IL-1β, and IL-6 were also found to be modulated in ISL group. The level of COX-2 and PGE2 was reduced to near normal after ISL administration together with increase in the IκBα expression and reduction of p65 and p-p65 expression in a concentration-dependent manner. The expression of iNOS wasalso found to be reduced in ISL group.
CONCLUSION: These results demonstrate that ISL causes protection of CLP-induced sepsis in experimental mice via multiple pathways.