Bacterial endotoxin stimulates macrophages / monocytes to release various cytokines
early (e.g., TNF-α, IL-1β, and IFN-γ) and late (HMGB-1) which then mediate sepsis
(or endotoxemia). HMGB1 recently discovered as late mediator of sepsis, is now seen
as one of main mediator of sepsis lethality and prompting investigations for
development of new drugs. Present study was undertaken to screen some novel target
for ameliorating HMGB1 release and investigate their effect in mice model of
endotoxemia.
Here we demonstrate that psychosine increases the HMGB1 in primary peritoneal
macrophage cells. The psychosine induced HMGB1 may have some interesting role
in pathobiology of Krabbe disease.
Aloe-emodin was seen to abrogate HMGB1 release dose dependently in both RAW
264.7 cells and primary peritoneal macrophage cells. The aloe-emodin was observed
to attenuate the release of pro-inflammatory cytokines (TNF-α, IL1β) and LPS –
induced oxidative stress markers iNOS, HO-1. The aloe-emodin showed protective
effect in endotoxemia rescuing mice from endotoxemia lethality. Aloe-emodin also
decreased the systemic accumulation of proinflammatory mediators (TNF-α, IL1-β)
within hours in endotoxemic mice. Endotoxemia induced multi-organ dysfunction
was also ameliorated by aloe-emodin treatment depicted by serum biochemistry
(ALT, ALP, BUN and creatinine) and histopathology of lung, liver and kidney. The
neutrophil infiltration was also reduced in lung tissues of aloe-emodin treated mice.
The inhibition of HMGB1 release by aloe-emodin and rescue of endotoxemic mice
makes aloe-emodin a potential candidate for sepsis therapy
