Protection Activity of 1,4-Naphthoquinones in Rotenone-Induced Models of Neurotoxicity

• Published in: Marine drugs Vol. 22; no. 2; p. 62
• Main Authors: Agafonova, Irina, Chingizova, Ekaterina, Chaikina, Elena, Menchinskaya, Ekaterina, Kozlovskiy, Sergey, Likhatskaya, Galina, Sabutski, Yuri, Polonik, Sergey, Aminin, Dmitry, Pislyagin, Evgeny
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-01-2024
• Subjects: 1,4-naphthoquinones; Analysis; Antioxidant properties; Antioxidants; Biocompatibility; Care and treatment; Cell cycle; Cell death; Cell viability; Cells; Cyclooxygenase-2; Cytokines; Cytotoxicity; Diagnosis; Health aspects; In vivo methods and tests; Inflammation; Low concentrations; Macrophages; Membrane potential; Microglia; Movement disorders; Neuroblastoma; Neuroblasts; Neurodegenerative diseases; neuronal cells; neuroprotection; Neurotoxicity; Neurotoxins; Nitric oxide; Oxidative stress; Parkinson's disease; Piscicides; Reactive oxygen species; Rotenone; Toxins; Russia; rotenone; 1,4-naphthoquinones; neuronal cells; macrophages; neuroprotection; Parkinson’s disease
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md22020062

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,
and
, 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,
and
, can protect neurons and microglia through their potent anti-ROS and anti-inflammatory activities.