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

Abstract：

OBJECT: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. METHODS: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. RESULTS: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. CONCLUSION: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.

journal_name

Arch Med Res

journal_title

Archives of medical research

authors

Deng LL

doi

10.1016/j.arcmed.2020.06.013

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

654-663

issue

eissn

0188-4409

issn

1873-5487

pii

S0188-4409(19)30969-5

journal_volume

pub_type

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