Protection Activity of 1,4-Naphthoquinones in Rotenone-Induced Models of Neurotoxicity
-
Published:2024-01-25
Issue:2
Volume:22
Page:62
-
ISSN:1660-3397
-
Container-title:Marine Drugs
-
language:en
-
Short-container-title:Marine Drugs
Author:
Agafonova Irina1ORCID, Chingizova Ekaterina1, Chaikina Elena1, Menchinskaya Ekaterina1, Kozlovskiy Sergey1ORCID, Likhatskaya Galina1, Sabutski Yuri1ORCID, Polonik Sergey1, Aminin Dmitry12ORCID, Pislyagin Evgeny1ORCID
Affiliation:
1. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, 690022 Vladivostok, Russia 2. Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, No. 100, Shin-Chuan 1st Road, Sanmin District, Kaohsiung City 80708, Taiwan
Abstract
The MTS cell viability test was used to screen a mini library of natural and synthetic 1,4-naphthoquinone derivatives (1,4-NQs) from marine sources. This screening identified two highly effective compounds, U-443 and U-573, which showed potential in protecting Neuro-2a neuroblastoma cells from the toxic effects of rotenone in an in vitro model of neurotoxicity. The selected 1,4-NQs demonstrated the capability to reduce oxidative stress by decreasing the levels of reactive oxygen species (ROS) and nitric oxide (NO) in Neuro-2a neuroblastoma cells and RAW 264.7 macrophage cells and displayed significant antioxidant properties in mouse brain homogenate. Normal mitochondrial function was restored and the mitochondrial membrane potential was also regained by 1,4-NQs after exposure to neurotoxins. Furthermore, at low concentrations, these compounds were found to significantly reduce levels of proinflammatory cytokines TNF and IL-1β and notably inhibit the activity of cyclooxygenase-2 (COX-2) in RAW 264.7 macrophages. The results of docking studies showed that the 1,4-NQs were bound to the active site of COX-2, analogically to a known inhibitor of this enzyme, SC-558. Both substances significantly improved the behavioral changes in female CD1 mice with rotenone-induced early stage of Parkinson’s disease (PD) in vivo. It is proposed that the 1,4-NQs, U-443 and U-573, can protect neurons and microglia through their potent anti-ROS and anti-inflammatory activities.
Funder
Russian Science Foundation
Subject
Drug Discovery,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Pharmaceutical Science
Reference58 articles.
1. Shen, X., Liang, X., He, C., Yin, L., Xu, F., Li, H., Tang, H., and Lv, C. (2023). Structural and pharmacological diversity of 1,4-naphthoquinone glycosides in recent 20 years. Bioorg. Chem., 138. 2. Epidemiology of Parkinson’s disease;Breteler;Lancet. Neurol.,2006 3. The prevalence of Parkinson’s disease: A systematic review and meta-analysis;Pringsheim;Mov. Disord.,2014 4. Parkinson’s disease;Kalia;Lancet,2015 5. Cacabelos, R. (2017). Parkinson’s Disease: From Pathogenesis to Pharmacogenomics. Int. J. Mol. Sci., 18.
|
|