Discovery of powerful multifaceted antioxidant for combating oxidative stress associated with neurodegenerative disorders.
10.1016/j.apsb.2025.04.024
- Author:
Juhee KHAN
1
;
Prabir Kumar GHARAI
1
;
Shubham GARG
2
;
Sanju GUPTA
2
;
Mohammad Umar ARSHI
2
;
Rathnam MALLESH
1
;
Surajit GHOSH
1
Author Information
1. Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India.
2. Department of Bioscience and Bioengineering, Indian Institute of Technology, Rajasthan 342037, India.
- Publication Type:Journal Article
- Keywords:
Antioxidant;
Hydrogen peroxide;
Ischemic stroke;
Neuroprotection;
Nrf2/ARE pathway;
Oxidative stress;
Polyphenol;
tBCCAO
- From:
Acta Pharmaceutica Sinica B
2025;15(9):4844-4871
- CountryChina
- Language:English
-
Abstract:
Amidst the tangled web of neurons, antioxidants stand as silent sentinels, shielding the delicate threads from the raging storm of oxidative stress in the realm of neurological affliction. Herein, we showcased an innovative design strategy to develop a novel powerful antioxidant small molecule (AOX), designed with the synergistic integration of EGCG (epigallocatechin gallate), gallic acid, and coupled with the metal-chelating capabilities of 8-hydroxy quinoline functional moieties that exhibit multifunctional activity in combating oxidative stress via activating the anti-oxidative, anti-apoptotic and anti-inflammatory activity, showcasing the potential for a transformative impact in neuroprotection from oxidative insults. Our work addresses oxidative stress in neuronal systems by providing a thorough examination of oxidative stress caused by hydrogen peroxide in PC12 cell line-derived neurons by shedding light on the antioxidative mechanisms orchestrated by our novel small molecule. Particularly our designed molecule (AOX) provides neuroprotection by mitigating mitochondrial impairment and activating the Nrf2/ARE (nuclear factor erythroid 2-related factor 2/antioxidant response element) pathway and it also demonstrates remarkable resilience against neuroinflammation, as evidenced by minimal alterations in neuroinflammatory markers such as GFAP, IBA1, and S100β in a transient bilateral common carotid artery occlusion (tBCCAO) ischemic stroke model.
