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

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.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.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.IPA exhibited neuroprotective activity against hyperglycaemic insults.