Dauricine combined with clindamycin inhibits severe pneumonia co-infected by influenza virus H5N1 and Streptococcus pneumoniae in vitro and in vivo through NF-κB signaling pathway

Dauricine, isolated from Menispermum dauricum, has been widely used for treatment of various diseases, including cardiac ischemia and inflammation-related diseases. However, little is known regarding to the effect of dauricine on severe pneumonia. Therefore, the aim was to investigate the effect of dauricine on severe pneumonia and its mechanism during progress. Herein, H5N1 and Streptococcus pneumoniae (D39) were conducted to induce severe pneumonia in both BEAS-2B cells and mice. In vitro, dauricine reversed the protein and mRNA expressions of TNF-α, IL-6 and IL-1β, examined by ELISA and qRT-PCR assay, respectively. In addition, the nuclear translocation of NF-κB/p65 and the phosphorylation expressions of IκBα and IKKα/β, examined by western blotting, were dose-dependently dropped by dauricine. However, dauricine had no significant effect on MAPKs, including JNK, ERK and p38. In vivo, dauricine significantly decreased MPO activity, the lung wet/dry weight ratio, the protein and mRNA expression of TNF-α, IL-6 and IL-1β, the expressions of NF-κB/p65, and attenuated the lung histological alterations. Besides, compared to dauricine alone, combined with clindamycin had more remarkably effects on severe pneumonia in vitro. Overall, the results suggested that dauricine, a relatively drug that targets NF-κB, in combination with clindamycin, maybe a novel therapeutic strategy for severe pneumonia.