Abstract
This study is the first demonstration of the neuroprotective activity of the marine alga, Spirulina maxima, fermented by Lactobacillus plantarum HY-08, which was freshly isolated from fermented vegetables. The combined process of the fermentation with ultrasonic extraction at 40 kHz for 4 hr greatly increased the amounts of β-carotene in the extract up to 1.62 mg/g, along with a high extraction yield of 18.26%, compared to 1.03 mg/g and 12.8% from ultrasonic extraction itself, and even much higher than 0.81 mg/g and 10.6% from conventional water extraction. It was also proved that the neuroprotective activities of the extract were enhanced possibly by higher contents of β-carotene in the extract, compared to those from water extraction or ultrasonic extraction itself. This extract was found to have strong antioxidant properties, with 49.01% 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, which resulted in 90.30% neuroprotective activity. Specifically, the fermented extract markedly enhanced the brain-derived neurotrophic factor (BDNF)/p-CREB signaling pathways, which can effectively prevent memory impairment in mice caused by oxidative stress. β-Carotene also increased the expression of p-CREB and BDNF, and a mechanism of their upregulation by β-carotene is first proposed in this study. It can be concluded that the strong neuroprotective effect of the extract was markedly influenced by the antioxidant activities, due to the synergistic effects of high amounts of β-carotene and other biologically active substances in the extract that can be obtained by lactic acid fermentation, combined with ultrasonic processing.
Highlights
Dementia is a degenerative brain disease characterized by a decline in learning, and there is a considerable increase of social interest in its prevention and treatment [1]
This study clearly showed, for the first time, that the extraction yield of β-carotene in the extracts of S. maxima was significantly increased by combining lactic acid fermentation with a nonthermal ultrasonic extraction process, using water as a solvent
This study was the first to prove that the increase of β-carotene content in the extracts greatly enhances its neuroprotective effects by efficiently suppressing the production of reactive oxygen species (ROS) and intracellular calcium ions in glutamate-induced HT22 cells, in addition to enhancing glutathione synthesis enzyme activity
Summary
Dementia is a degenerative brain disease characterized by a decline in learning, and there is a considerable increase of social interest in its prevention and treatment [1]. The mechanisms underlying the phenomena of the decline in memory and cognitive functions have been understood to be an excessive accumulation of amyloid β protein in the brain [2]. Neurological degeneration resulting from nerve cell damage occurring during the decomposition of acetylcholine (ACh) by acetylcholinesterase (AChE) has been considered to be a major mechanism that is associated with dementia [2,3]. Prolyl endopeptidase (PEP) is a protease that is known to be highly involved in the generation of amyloid β protein, and it digests proline, and it is one of key neuropeptides in the cerebral cortex of the brain [4,5]; PEP inhibitors have been developed as therapeutic agents to overcome declines in memory and cognitive function.
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