Sinomenine modulates the metabolic reprogramming induced by sepsis via CHRNA7

Abstract

Background and purpose

Sepsis is a condition capable of causing systemic inflammation and metabolic reprogramming. Previous studies have shown that sinomenine (SIN) can mitigate sepsis by reducing inflammation, while the effect on metabolic reprogramming is unclear. The aim of this study is to investigate the function of SIN in metabolic reprogramming in sepsis.

Experimental approach

Differential metabolites in lung tissue and serum were analyzed by 1H Nuclear Magnetic Resonance (¹H NMR) and metabolomics were used to compare metabolic changes in septic mice. Nicotinic acetylcholine receptors alpha7 subunit (CHRNA7)-Knockdown (KD) mice and other techniques, were used to detect the expression of markers of several metabolic pathways.

Key results

Metabolomics studies showed that SIN could affect energy metabolism, particularly glucose metabolism, and this effect may be related to the activation of CHRNA7. Further studies showed that SIN could inhibit aerobic glycolysis, promote glutamine anaplerosis, reduce pentose phosphate pathway flux and ultimately mediate metabolic reprogramming.

Conclusion and implications

SIN restores glycolysis and glutamine anaplerosis by interacting with CHRNA7, thereby mediating metabolic reprogramming and mitigating sepsis. These findings shed light on the mechanism of SIN in attenuating sepsis from a metabolic perspective.