Abstract
Beyond their significant contribution to the dietary and industrial supplies, marine algae are considered to be a potential source of some unique metabolites with diverse health benefits. The pharmacological properties, such as antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance and anti-amyloidogenic potentials of algal metabolites endorse their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis which are known to be implicated in the pathophysiology of neurodegenerative disorders and the associated complications after cerebral ischemia and brain injuries. As was evident in various preclinical studies, algal compounds conferred neuroprotection against a wide range of neurotoxic stressors, such as oxygen/glucose deprivation, hydrogen peroxide, glutamate, amyloid β, or 1-methyl-4-phenylpyridinium (MPP+) and, therefore, hold therapeutic promise for brain disorders. While a significant number of algal compounds with promising neuroprotective capacity have been identified over the last decades, a few of them have had access to clinical trials. However, the recent approval of an algal oligosaccharide, sodium oligomannate, for the treatment of Alzheimer’s disease enlightened the future of marine algae-based drug discovery. In this review, we briefly outline the pathophysiology of neurodegenerative diseases and brain injuries for identifying the targets of pharmacological intervention, and then review the literature on the neuroprotective potentials of algal compounds along with the underlying pharmacological mechanism, and present an appraisal on the recent therapeutic advances. We also propose a rational strategy to facilitate algal metabolites-based drug development.
Highlights
Neurons and supporting cells of the brain encounter degenerative changes during physiological or pathological aging, ischemic stroke, or other brain injuries [1]
Ina and colleagues demonstrated that the neurodifferentiation of PC12 cells by pheophytin a of Sargassum fulvellum required the presence of nerve growth factor (NGF) and involved the activation of an mitogen-activated protein kinase (MAPK) signaling pathway [147]
The current review highlights several neuropharmacological attributes, such as antioxidant, anti-inflammatory, anti-cholinesterase, anti-amyloidogenic, antiaging, protein clearance, cholesterol homeostasis, and neuritogenic capacity of algae-derived metabolites that underlie their neuroprotective functions against a wide range of neurotoxic stimuli (Figure 5)
Summary
Neurons and supporting cells of the brain encounter degenerative changes during physiological or pathological aging, ischemic stroke, or other brain injuries [1]. Algal metabolites, such as phenolics, alkaloids, terpenoids, carotenoids, phytosterols, and polysaccharides have attracted much attention to medicinal chemistry due to their structural uniqueness and functional diversity [17,18,19,20] These biofunctional compounds have shown to provide neuroprotection in preclinical models of neurodegenerative diseases, ischemic stroke, brain trauma, diabetes, and obesity, among many others, owing to their antioxidant, anti-inflammatory, and immunomodulatory capacities [21,22,23,24,25,26,27,28]. Addressing the knowledge gap and the possible limitations, offering a comprehensive review updating information on the neuroprotective effects of algal compounds and their therapeutic advances is timely In this comprehensive review, we first briefly outline the pathobiology of neurodegenerative disorders, ischemic stroke, and traumatic brain injury and provide pharmacological insights into the neuroprotective potentials of algal metabolites and highlight the recent progress in algae-based drug discovery. The rational strategy for algal compounds-based drug development has been discussed
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