Anti-influenza A Virus Effects and Mechanisms of Emodin and Its Analogs via Regulating PPARα/γ-AMPK-SIRT1 Pathway and Fatty Acid Metabolism

Figure 8

PPARα/γ-AMPK pathway and fatty acid metabolism played important roles in emodin-mediated inhibition of IAV infection in mice. In the normal control (normal), mice were not infected with IAV but intranasally shammed with VGM medium. In the only IAV-infected (IAV) and oseltamivir- (Ose-) and emodin- (EMO-) treated groups, mice were infected with 10x MLD50 of IAV (PR8) and treated with PBS+DMSO (<0.5%), oseltamivir (10 mg/kg/d), and emodin (75 mg/kg/d) from -1 to 5 d p.i., respectively. In the antagonism groups, IAV-infected mice were treated with emodin (75 mg/kg/d) by oral gavage and simultaneously treated with the inhibitors of PPARα (MK886, 1 mg/kg/d), PPARγ (GW9662, 2 mg/kg/d), AMPK (CC, 20 mg/kg/d), β-oxidation inhibitor (ETO, 30 mg/kg/day), and fatty acid palmitate (PA, 300 mg/kg/day) by intraperitoneal injection from -1 to 5 p.i., respectively. The survival rates were observed for 14 days. The pulmonary cytokine and viral load were determined by ELISA and TCID50 assays, respectively. The lung index was evaluated by determining the percent of lung wet weight (g) to body weight (g) (). vs. the IAV-infected group; ^# vs. the IAV+emodin group.

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