Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway

Area of Science:

• Pharmacology
• Immunology
• Molecular Biology

Background:

• Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection.
• Lipopolysaccharide (LPS) is a key component of Gram-negative bacteria that triggers inflammatory responses in sepsis.
• Traditional Chinese Medicine (TCM) formulations, like Fangji Fuling Decoction (FFD), are explored for their therapeutic potential in sepsis.

Purpose of the Study:

• To investigate the therapeutic effects of Fangji Fuling Decoction (FFD) on sepsis.
• To elucidate the underlying molecular mechanisms of FFD action using network pharmacology.
• To validate findings through in vitro and in vivo experimental models.

Main Methods:

• Sepsis models were established in mice (LPS injection) and RAW264.7 macrophages (LPS stimulation).
• Network pharmacology identified key pathways involved in FFD's action on sepsis.
• In vitro and in vivo experiments assessed FFD's impact on organ damage, inflammation, cell apoptosis, and the MAPK14/FOXO3A signaling pathway.

Main Results:

• FFD significantly reduced organ damage and inflammation in LPS-induced septic mice.
• FFD suppressed LPS-induced macrophage apoptosis and inflammation in vitro.
• Network pharmacology and experimental validation confirmed FFD inhibits the MAPK14/FOXO3A signaling pathway, mitigating sepsis-induced inflammation and apoptosis.

Conclusions:

• FFD demonstrates therapeutic potential in ameliorating sepsis.
• Inhibition of the MAPK14/FOXO3A signaling pathway is a key mechanism by which FFD exerts its anti-inflammatory and anti-apoptotic effects in sepsis.
• FFD offers a promising therapeutic strategy for managing sepsis-related inflammatory responses.