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Neuroprotective potential of esterified indole-3-propionic acid with curcumin against high glucose stress: targeting
Jayanthi Sidhambaram1, Chitra Loganathan2, Penislusshiyan Sakayanathan3
1Department of Biochemistry, Periyar University, Salem, Tamil Nadu, 636011, India.
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.
Insights
This study shows that curcumin-indole-3-propionic acid conjugate (CUR-IPA) protects against high glucose-induced neurodegeneration in neuronal cells. CUR-IPA improves cell viability and reduces oxidative stress, suggesting potential for treating diabetes-related brain changes.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Type 2 diabetes mellitus (T2DM) is associated with neurodegeneration, driven by oxidative stress and mitochondrial dysfunction.
- Chronic hyperglycemia in T2DM exacerbates these neurodegenerative processes.
- Understanding these mechanisms is crucial for developing effective therapies.
Purpose of the Study:
- To evaluate the neuroprotective effects of a novel curcumin-indole-3-propionic acid conjugate (CUR-IPA).
- To assess CUR-IPA's efficacy against high glucose (HG)-induced neuronal damage in SH-SY5Y cells.
- To investigate CUR-IPA's impact on oxidative stress, mitochondrial function, and key signaling pathways.
Main Methods:
- SH-SY5Y cells were exposed to high glucose (HG) to mimic diabetic conditions.
- Cells were co-treated with varying concentrations of CUR-IPA.
- Assays included cell viability, oxidative stress markers, mitochondrial membrane potential (MMP), and apoptosis.
- Flow cytometry quantified protein expression related to apoptosis, survival, and neurotrophic signaling.
Main Results:
- HG exposure induced significant oxidative stress, reduced MMP, and increased apoptosis in neuronal cells.
- HG suppressed the PI3K/Akt/mTOR and BDNF/TrkB/CREB survival pathways.
- CUR-IPA treatment dose-dependently counteracted HG-induced damage, preserving cell viability and restoring signaling pathways.
Conclusions:
- CUR-IPA exhibits significant neuroprotective properties against high glucose-induced cellular damage.
- The conjugate modulates redox status, enhances mitochondrial function, and supports survival signaling pathways.
- CUR-IPA shows promise as a multi-target therapeutic agent for neurodegeneration associated with T2DM, meriting further in vivo investigation.