Siji Antiviral Mixture Protects against CA16 Induced Brain Injury through Inhibiting PERK/STAT3/NF-κB Pathway

Coxsackievirus 16 (CA16) causes hand, foot, and mouth disease (HFMD) in young children and infants, and it can lead to fatal neurological complications. This study investigated antiviral effects of Siji Antiviral Mixture (SAM) on CA16 in neonatal mice and the protective effects of SAM on CA16 induced brain injuries. Neonatal BALB/c mice and SH-SY5Y cells were used and injected with CA16 stains to study the efficacy. ELISA and Western blotting were used to measure the cytokines levels and proteins expression. Genes transduction was also used to verify interaction mechanism. As the results shown, SAM could reduce the clinical scores at the beginning and delay disease development in vivo. Treatment with SAM decreased the levels of LDH, CK-MB, caspase 3 and Bax, ER stress, and inflammatory reaction induced by CA16 infection. Further siRNA transfection results showed that CA16 induced ER stress and inflammatory reaction through PERK/STAT3/NF-κB signaling and the protective effects of SAM might be through inhibiting PERK/STAT3/NF-κB signaling. HPLC analysis showed fingerprint profiles of SAM had 42 chromatographic peaks. Collectively, our study highlighted distinct roles of SAM in inhibiting CA16 infection and brain injury. The molecular mechanism of SAM might be through inhibiting PERK/STAT3/NF-κB signaling.