Indole-3-propionic acid attenuates high glucose induced ER stress response and augments mitochondrial function by modulating PERK-IRE1-ATF4-CHOP signalling in experimental diabetic neuropathy

Abstract

Objectives

We aimed to evaluate the neuroprotective effect of Indole-3-propionic acid (IPA) against streptozotocin (STZ) induced diabetic peripheral neuropathy (DPN) in rats and in high glucose (HG) induced neurotoxicity in neuro2a (N2A) cells.

Methods

Diabetes was induced in male SD rats STZ (55 mg/kg, i.p.) and IPA (10 and 20 mg/kg, p.o.) was administered for two weeks, starting from sixth week after diabetes induction. Neurobehavioral, functional assessments were made, and various molecular studies were performed to evaluate the effect of IPA on HG induced ER stress and mitochondrial dysfunction in sciatic nerves, DRGs and in N2A cells.

Results

Diabetic rats and high glucose exposed N2A cells showed marked increase in oxidative damage accompanied by ER stress and mitochondrial dysfunction along with increased apoptotic markers. IPA treatment for two weeks markedly alleviated these changes and attenuated pain behaviour.

Conclusion

IPA exhibited neuroprotective activity against hyperglycaemic insults.

Keywords:

• Indole-3-propionic acid
• ER stress
• mitochondrial dysfunction
• diabetic neuropathy
• neuro2a cells

Disclosure statement

The authors have no conflicts of interest to declare.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author upon reasonable request.

Additional information

Funding

The authors are grateful for the financial support of Department of Science and Technology (DST), Women Scientist Scheme-A (WOS-A) [grant number: SR/WOS-A/LS-485/2017] to carry out this study and NIPER-Hyderabad, India, in the preparation of this paper.