Discovery of Gallic Acid-Based Mitochondriotropic Antioxidant Attenuates LPS-Induced Neuroinflammation.

Autor: Garg S; Department of Bioscience and Bioengineering, Indian Institute of Technology, Jodhpur, NH 62, Surpura Bypass Road, Karwar, Rajasthan 342037, India., Jana A; Smart Healthcare, Interdisciplinary Research Platform, Indian Institute of Technology Jodhpur, Karwar, Rajasthan, 342037, India., Gupta S; Department of Bioscience and Bioengineering, Indian Institute of Technology, Jodhpur, NH 62, Surpura Bypass Road, Karwar, Rajasthan 342037, India., Arshi MU; Department of Bioscience and Bioengineering, Indian Institute of Technology, Jodhpur, NH 62, Surpura Bypass Road, Karwar, Rajasthan 342037, India., Gharai PK; Department of Bioscience and Bioengineering, Indian Institute of Technology, Jodhpur, NH 62, Surpura Bypass Road, Karwar, Rajasthan 342037, India; Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Raja S. C. Mullick Road, Jadavpur, Kolkata-700 032, West Bengal, India., Khan J; Department of Bioscience and Bioengineering, Indian Institute of Technology, Jodhpur, NH 62, Surpura Bypass Road, Karwar, Rajasthan 342037, India; Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Raja S. C. Mullick Road, Jadavpur, Kolkata-700 032, West Bengal, India., Roy R; Department of Bioscience and Bioengineering, Indian Institute of Technology, Jodhpur, NH 62, Surpura Bypass Road, Karwar, Rajasthan 342037, India., Ghosh S; Department of Bioscience and Bioengineering, Indian Institute of Technology, Jodhpur, NH 62, Surpura Bypass Road, Karwar, Rajasthan 342037, India; Smart Healthcare, Interdisciplinary Research Platform, Indian Institute of Technology Jodhpur, Karwar, Rajasthan, 342037, India; Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Raja S. C. Mullick Road, Jadavpur, Kolkata-700 032, West Bengal, India. Electronic address: sghosh@iitj.ac.in.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2024 Nov 18. Date of Electronic Publication: 2024 Nov 18.
DOI: 10.1016/j.freeradbiomed.2024.11.020
Abstrakt: Mitochondria are complex organelle that plays a pivotal role in energy metabolism, regulation of stress responses, and also serve as a major hub for biosynthetic processes. In addition to their well-established function in cellular energetics, it also serves as the primary site for the origin of intracellular reactive oxygen species (ROS), which function as signaling molecules and can lead to oxidative stress when generated in excess. Moreover, mitochondrial dysfunction is one of the leading cause of neuroinflammation. In this regard, we have rationally designed a triazine derived mitochondriotropic antioxidants (Mito-TBA), based on gallic acid and triphenylphosphonium (TPP) cation to specifically target mitochondria to mitigate neuroinflammation. In vitro Mito-TBA-3 inhibits mitoautophagy, offers neuroprotection by inhibiting the LPS induced TLR-4 activation and activating the Nrf-2/ ARE pathway in PC-12 derived neurons. In vivo Mito-TBA-3 rescue memory deficit, reversed depression like behavior, inhibited neuroinflammation, and decreased proinflammatory cytokines in LPS induced neuroinflammation rat model. Overall, based on biophysical, in vitro and in vivo analysis, Mito-TBA-3 offers valuable insights as a potent therapeutic lead molecule to combat neurodegeneration even outperforming a well-known non-steroidal anti-inflammatory drug (Aspirin), it also has the potential to use as a promising therapeutic candidate for other mitochondrial oxidative stress related disorders.
Competing Interests: Declaration of Competing Interest The authors of this manuscript declare that this manuscript was written without the use of generative AI or AI-assisted technology to improve readability, language, or any other part of the writing. The thoughts, analyses, and conclusions provided are the outcome of human endeavour and intellectual contribution.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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