Background: Acute kidney injury (AKI) is one of the most critical care conditions with various etiologies and high mortality. LPS induces AKI by activation of renal inflammatory cascade, promotes the release of numerous pro-inflammatory cytokines, and ultimately results in kidney damage. Gentiopicroside, a natural secoiridoid glycoside extracted from Gentiana lutea with gastroprotective and hepatoprotective effects. In this study, the renoprotective and anti-inflammatory effects of gentiopicroside were investigated in a mouse model of LPS-induced acute kidney injury.
Method: AKI induced in mice by LPS 10mg/kg/day intraperitoneally and euthanized 24 hrs later. Mice in the treatment groups received either 40mg or 80mg/kg/day of oral gentiopicroside for 5 consecutive days prior to LPS injection.
Results: The renoprotective effect of gentiopicroside (40mg/kg/day) resulted from the significant reduction of kidney injury marker (KIM-1) mRNA expression level in kidney tissue (5.23±1.06 vs. 25.46±2.32) compared to nontreated mice. An interested dose dependent renoprotective effect observed with further significant reduction of KIM-1 mRNA level when 80mg/kg/day were used (2.42±0.65 vs. 25.46±2.32) compared to nontreated mice. Pretreatment with Gentiopicroside 40 and 80 mg/kg/day revealed strong and dose dependent anti-inflammatory effect as observed from the significant attenuation of the inflammatory markers IL-1β (21.66±2.17 and 7.13±1.50 vs. 49.08±5.23) and iNOS (9.73±1.85 and 3.98±1.44 vs. 40.87±5.59) mRNA expression levels in kidney tissue compared to nontreated mice. Further investigation of the upstream mediators revealed that gentiopicroside exerted strong hampering effects on NF-κB (0.42±0.07 and 0.21±0.12 vs. 7.66±1.39), AP-1 (1.59±0.60 and 0.71±0.21 vs. 15.27±1.66) and IRF3 (4.89±0.76 and 4.16±1.015 vs. 19.21±3.06) mRNA expression level in kidney tissue compared to nontreated mice significantly.
Conclusion: This study clearly revealed that gentiopicroside exerted a dose dependent anti-inflammatory and kidney protective effects in LPS-induced acute kidney injury. The observed effects were resulted through hampering of NF-κB, AP-1 and IRF3 pathways.
