Background and objectives

Cytokine storm (CS) is an acute systemic inflammatory response with limited effective interventions up to now. The treatment experience of the COVID-19 pandemic suggests great potential in the intervention of CS by herbal medicine. This study aimed to investigate whether Schisanhenol (SSH), an active component of the Chinese herbal medicine Schisandra chinensis, has the potential to interfere with CS.

Methods

The effect of SSH on nuclear factor-kappa B (NF-κB) signaling pathway activity was observed with THP-1/NF-κB cells. THP-1 and abdominal macrophages were used as cell models to observe the effect of SSH on inflammatory responses. The lipopolysaccharide-induced acute inflammatory response in mice was used to observe the effect of SSH on systemic inflammatory response and induced acute lung injury. The potential biological mechanism of SSH against inflammatory storm was explored by network pharmacology and molecular docking methods.

Results

SSH significantly inhibited NF-κB pathway activity and suppressed macrophage and systemic inflammatory responses in mice. SSH also effectively alleviated lipopolysaccharide-induced acute lung injury. The network pharmacology results showed that estimated glomerular filtration rate, matrix metalloproteinase 9, proto-oncogene tyrosine-protein kinase Src, and mammalian target of rapamycin are potential key target proteins of SSH.

Conclusions

The findings of this study demonstrate that SSH inhibited the macrophage inflammatory response and cytokine production at both the systemic and local levels in mice. Additionally, SSH effectively mitigated acute lung injury resulting from CS. Furthermore, network pharmacological analysis revealed that SSH has the ability to suppress inflammatory response through multiple mechanisms.