Baicalein triazole prevents respiratory tract infection by RSV through suppression of oxidative damage

Abstract

Baicalein, an isolate of secutellaria baicalensis is known for its anti-inflammatory activity. In the present study, 12-triazole derivatives of baicalein were synthesized and evaluated against RSV infected BEAS-2B cells in vitro and in mice model in vivo. The preventive effect of most active compound 5f against RSV infection was studied in detail. The compound 5f treatment increased IFN-β1 expression in BEAS-2B cells infected with RSV. In BEAS-2B cells treatment with compound 5f inhibited RSV-induced secretion of interleukin-6 and -8 cytokines. It decreased RSV-induced nitric oxide & malondialdehyde production and inhibited the RSV-mediated activation of NF-κB, COX-2, Stat3 and MAPK. The p38 phosphorylation was enhanced significantly in RSV infected cells by compound 5f pre-treatment. RT-qPCR showed that compound 5f treatment of the RSV-infected mice significantly (P < 0.05) decreased viral load through reduction in the viral replication. In the mice model of RSV-infection compound 5f treatment decreased interleukin-6, -8 and tumor necrosis factor-α expression. The level of MPO, nitric oxide and malondialdehyde was also decreased significantly by compound 5f in the RSV infected mice BALF. It also reduced the infiltration of neutrophils and lymphocytes in the BALF of RVS-infected mice. In summary, compound 5f inhibits RSV-infection and prevents pulmonary airway inflammation through the activation of IFN signalling pathway.