Ribisins and Certain Analogues Exert Neuroprotective Effects through Activation of the Keap1‐Nrf2‐ARE Pathway
| Autor: | Shen H. Tan, Muthukumar Karuppasamy, Ping Lan, Yaochun Zhang, Jiayi Hu, Xingchen Lai, Belinda Siok‐Cheng Lim, Weiliang Liu, Jing Chen, Eng‐Hui Chew, Martin G. Banwell |
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| Rok vydání: | 2022 |
| Předmět: |
Pharmacology
Biological Products Kelch-Like ECH-Associated Protein 1 NF-E2-Related Factor 2 Organic Chemistry NAD Biochemistry Antioxidants Rats Iodoacetamide Mice Neuroblastoma Oxidative Stress Neuroprotective Agents Heme Oxygenase (Decyclizing) Drug Discovery Animals Humans Molecular Medicine Cysteine General Pharmacology Toxicology and Pharmaceutics |
| Zdroj: | ChemMedChem. 17 |
| ISSN: | 1860-7187 1860-7179 |
| Popis: | Oxidative stress contributes to the pathogenesis of various neurodegenerative diseases and induction of the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is a validated neuroprotective strategy. Synthetically-derived samples of members of the ribisin class of natural product together with a range of analogues were evaluated for their neuroprotective capacities. Four of the twenty-four compounds tested were found to strongly stimulate antioxidant response element-dependent transcriptional activity in human-derived SH-SY5Y cells. Further, in rat pheochromocytoma PC12 cells and mouse brain cortical cultures these compounds upregulated levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target gene products, namely heme oxygenase (HO-1) and NAD(P)H quinone reductase 1 (NQO1). Functionally speaking, the compounds conferred protection in these cell models challenged with H |
| Databáze: | OpenAIRE |
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