Tubeimoside III inhibits lipopolysaccharide-induced inflammatory
responses by reprogramming glycolytic metabolism
Abstract
OBJECTIVE To investigate how tubeimoside III inhibits
lipopolysaccharide(LPS)-induced inflammatory responses by reprogramming
glucose metabolism. METHOD A mouse model of LPS-induced acute
inflammation was constructed, and the protective effect of tubeimoside
III against LPS-induced injury was investigated using histochemistry and
real-time quantitative PCR. Western blotting, Seahorse extracellular
flux analyser assays, and pyruvate content assays were used in
LPS-induced RAW264.7 cells to explore how tubeimoside III exerts its
anti-inflammatory effects. The potential mechanism was also validated
using inhibitors. RESULTS Tubeimoside III significantly
attenuated the expression of inflammatory cytokines IL-6, IL-1β, and
iNOS in lung and liver tissue homogenates and RAW264.7 cells. This agent
inhibited inflammatory cell infiltration in alveoli and prevented
necrosis in liver lesions in LPS-treated mice. Extracellular flux
analyser assays revealed that tubeimoside III regulated glucose
metabolism in RAW264.7 cells. Real-time quantitative PCR and western
blot revealed that tubeimoside III had similar effects on the downstream
effector molecule of itaconic acid. An inhibitor weakened the inhibitory
effect of tubeimoside III on the expression of inflammatory factors.
CONCLUSIONS Tubeimoside III protects against LPS-induced lung
and liver injury by attenuating inflammatory factor secretion and
inflammatory cell infiltration, and its mechanism of action involves
reprogramming macrophage glucose metabolism and increasing itaconic acid
levels.