The anti-rotavirus effect of baicalin via the gluconeogenesis-related p-JNK-PDK1-AKT-SIK2 signaling pathway.

Rotavirus (RV) infection is a leading cause of severe, dehydrating gastroenteritis in children < 5 years of age, and by now, the prevention and treatment of RV are still the major public health problems due to a lack of specific clinical drugs. Thus, the aims of this study are to explore the anti-RV effect of baicalin and its influence on glucose metabolism. Here, we demonstrated for the first time that baicalin had an anti-RV attachment effect with the strongest effect at a concentration of 100 μM, and also inhibited the replication of RV at concentrations of 100, 125, 150, 175, and 200 μM. Moreover, baicalin helped to overcome the weight loss and reduced the diarrhea rate and score with the best therapeutic effect at a concentration of 0.3 mg/g in RV-infected neonatal mice. Interestingly, baicalin decreased glucose consumption in RV-infected Caco-2 cells with the optimal concentration of 125 μM. Next, metabolomic analysis indicated that there were 68 differentially expressed metabolites, including an increase in pyruvic acid, asparagine, histidine and serine, and a decrease in dihydroxyacetone phosphate, which suggested that the underlying signaling pathway was gluconeogenesis. Further studies demonstrated that baicalin inhibited gluconeogenesis via improving glucose 6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxylase (PEPCK). Moreover, baicalin upregulated the potential gluconeogenesis proteins named salt inducible kinase 2, pyruvate dehydrogenase kinase 1, AKT serine/threonine kinase 1 and down-regulated phosphorylated c-Jun NH2-terminal kinase, which are associated with G-6-Pase and PEPCK expressions. Therefore, baicalin improved the gluconeogenesis disruption caused by RV.