Astragaloside IV as Potential Antioxidant Against Diabetic Ketoacidosis in Juvenile Mice Through Activating JNK/Nrf2 Signaling Pathway

Abstract

Astragaloside IV (AS IV) has antioxidative and anti-apoptotic properties, however, its effects on juvenile mice with diabetic ketoacidosis (DKA) have not been determined. This study aims to explore the effect and mechanism of Astragaloside IV (AS-IV) on juvenile mice with DKA. DKA model was established through intraperitoneal injection of streptozotocin (STZ) and alloxan (ALX). DKA mice were divided into Control group, DKA group, DKA+AS-IV group, DKA+AS-IV+SP600125 group, DKA+AS-IV+Anisomycin group, DKA+AS-IV+GV248 group and DKA+AS-IV+GV248-Nrf2 group. To verify the implication of JNK signal pathway, JNK inhibitor SP600125 and activator Anisomycin were injected. The effects of AS-IV on antioxidant capacity and pathologies of pancreatic tissues in DKA juvenile mice were assessed. The expression of JNK/Nrf2 signal pathway was measured by Western blot. DKA juvenile mouse models were successfully established, evidenced by elevated blood glucose and blood ketone, suppressed insulin and pH value, and notable injuries in pancreatic tissues. Gavage of AS-IV can enhance antioxidant capacity of pancreatic tissue and ameliorate injuries in pancreatic tissues. AS-IV increased insulin level, in addition to suppressing blood glucose in DKA juvenile mice. In pancreatic tissues of DKA juvenile mice, protein level of p-JNK/JNK in pancreatic tissue and Nrf2 in the nuclei were increased after administration of AS-IV. Inhibition on JNK/Nrf2 signal pathway would impair the favorable effect of AS-IV on DKA juvenile mice, while antioxidant capacity, insulin level and blood glucose were improved in DKA juvenile mice injected an activator of JNK/Nrf2 pathway. Collectively, AS-IV can enhance the antioxidant capacity of DKA juvenile mice to decrease blood glucose and to increase serum insulin secretion. The mechanism of action may be realized through the JNK/Nrf2 pathway.