Fucoxanthin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE and Nrf2-autophagy pathways

Abstract

Fucoxanthin is abundant in seaweed and is considered as a powerful antioxidant. It has been proposed to possess anti-cancer, anti-obesity and anti-diabetes effects. However, its roles in brain injury models have not been fully understood. The objective of this study was to investigate the neuroprotection of fucoxanthin in models of traumatic brain injury (TBI) and the role of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant-response element (ARE) and Nrf2-autophagy pathways in the putative neuroprotection. We found that fucoxanthin alleviated TBI-induced secondary brain injury, including neurological deficits, cerebral edema, brain lesion and neuronal apoptosis. Moreover, the up-regulation of malondialdehyde (MDA) and the activity of glutathione peroxidase (GPx) were reversed by fucoxanthin treatment. Furthermore, our in vitro studies demonstrated that fucoxanthin increased the neuron survival and reduced the reactive oxygen species (ROS) level. In addition, fucoxanthin activated the Nrf2-ARE pathway and autophagy both in vivo and in vitro, which was proven by the results of immunohistochemistry, western blot and electrophoretic mobility shift assay (EMSA). However, fucoxanthin failed to provide neuroprotection and activated autophagy following TBI in Nrf2−/− mice. In conclusion, our studies indicated that fucoxanthin provided neuroprotective effects in models of TBI, potentially via regulation of the Nrf2-ARE and Nrf2-autophagy pathways.

Antioxidant Therapies in Traumatic Brain Injury

“…Results showed that astaxanthin administration improved sensorimotor performance and enhanced cognitive recovery. In addition, reduction of lesion size in the cortex and expressions comparable to controls of brain-derived neurotrophic factor (BDNF), growth-associated protein-43 (GAP-43), synapsin, and synaptophysin (SYP), indicating the induction of neuronal survival and plasticity, were recorded [105].…”

Role of mitochondrial calcium uniporter‐mediated Ca2+ and iron accumulation in traumatic brain injury

“…The culture of mouse cortical neurons was performed according to previous studies. 17,18 In brief, mouse cortical neurons were isolated from the embryos of time-mated pregnant mice and subsequently cultured in poly-D-lysine-coated six-well dishes at a density of 1 × 10 6 cells per well. Then, the neurons were cultured in neurobasal medium (Life Technologies, USA, catalogue number: 21103049) supplemented with 2% B27 (Life Technologies, USA, catalogue number: 17504044) and 1 mmol/L glutamate (Sigma Aldrich, USA, catalogue number: G3291) at 37°C on 5% CO 2 incubator.…”

“…based on our previous studies. 18 In brief, the sections were incubated with labelling solution containing TUNEL at 37°C for 1 hour.…”

Fucoxanthinol from the Diatom Nitzschia Laevis Ameliorates Neuroinflammatory Responses in Lipopolysaccharide-Stimulated BV-2 Microglia

“…Moreover, Fuol possesses various beneficial biological activities such as antioxidation [26], prevention of different types of cancers [27], and protection of central nervous system neurons [28]. Although some reports suggest that fucoxanthin could alleviate TBI-induced secondary brain injury and attenuate scopolamine-induced cognitive impairments in mice, seldom reports have claimed the role of Fuol in those brain diseases [29,30]. In particular, the effects of Fuol on neuroinflammation in microglia and neuroinflammatory-related diseases are unclear.…”