Neuroprotective potential of esterified indole-3-propionic acid with curcumin against high glucose stress: targeting oxidative damage, Akt/mTOR, and BDNF/TrkB pathways.

INTRODUCTION

Type 2 diabetes mellitus (T2DM) is increasingly linked to neurodegenerative changes driven by oxidative stress, mitochondrial dysfunction, and dysregulated signaling pathways, particularly under chronic hyperglycemia.

AIM: This study aimed to assess the neuroprotective effects of novel curcumin-indole-3-propionic acid conjugate (CUR-IPA) against high glucose (HG)-induced damage in SH-SY5Y neuronal cells.

METHODS

Cells were exposed to HG to simulate diabetic stress and co-treated with CUR-IPA (6.25-25 µM). Cell viability, oxidative stress markers, mitochondrial membrane potential (MMP), and apoptosis were evaluated. Flow cytometry was used to quantify the expression of apoptotic (p53, Bax, caspase-3, and Bcl-2), survival (p-Akt and mTOR), and neurotrophic (BDNF, p-TrkB, and CREB) proteins.

RESULTS

HG induced oxidative stress, loss of MMP, apoptosis, and suppression of PI3K/Akt/mTOR and BDNF/TrkB/CREB pathways.

CONCLUSION

In conclusion, CUR-IPA demonstrates strong neuroprotective potential under HG stress by modulating redox status, mitochondrial function, and survival signaling. The findings suggest its promise as a multi-target therapy for diabetes-linked neurodegeneration, and warrant an in vivo study.

CLINICAL TRIAL NUMBER: Not applicable.