Fucosterol inhibits the cholinesterase activities and reduces the release of pro-inflammatory mediators in lipopolysaccharide and amyloid-induced microglial cells

Wong, Chun Hoong; Gan, Sook Yee; Tan, Swee Ching; Gany, Siti Aisya; Ying, Tiong; Gray, Alexander; Igoli, John O.; Chan, Elaine Wan Ling; Phang, Siew Moi

doi:10.1007/s10811-018-1495-1

Cited by 32 publications

(17 citation statements)

References 68 publications

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“…However, AD pathology is accompanied by the cholinergic deficit, which could be compensated by the AChE inhibitor. Previous studies showing the inhibitory activity of fucosterol against AChE [12,28] and our molecular docking findings suggest that fucosterol could be a promising AChE inhibitor having clinical application in AD.…”

Section: Discussionsupporting

confidence: 67%

“…Fucosterol is an algal sterol, which is isolated mostly from brown algae, indicating its abundance in this particular algal class. Evidence from the literatures supports its various biological activities, including antioxidant [6,7,8,9], anti-inflammatory [7,8,10,11,12,13], anticancer [14,15], antidiabetic [16], cholesterol homeostasis [17], cholesterol-lowering [18], antihyperlipidemic [19], hepatoprotective [6,20,21], immunostimulatory [22], antimicrobial [23], antiobesity [24,25], and antidepressant [26] potentials. Moreover, fucosterol exhibits inhibitory activity against acetyl- and butyryl-cholinesterase (AChE and BChE) [27,28] and β-secretase (an enzyme responsible for Aβ production, which is related to Alzheimer’s disease) [29].…”

Section: Introductionmentioning

confidence: 99%

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Deciphering Molecular Mechanism of the Neuropharmacological Action of Fucosterol through Integrated System Pharmacology and In Silico Analysis

et al. 2019

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Fucosterol is an algae-derived unique phytosterol having several medicinal properties, including antioxidant, anti-inflammatory, anticholinesterase, neuroprotective, and so on. Accumulated evidence suggests a therapeutic promise of fucosterol in neurodegeneration; however, the in-depth pharmacological mechanism of its neuroprotection is poorly understood. Here, we employed system pharmacology and in silico analysis to elucidate the underlying mechanism of neuropharmacological action of fucosterol against neurodegenerative disorders (NDD). Network pharmacology revealed that fucosterol targets signaling molecules, receptors, enzymes, transporters, transcription factors, cytoskeletal, and various other proteins of cellular pathways, including tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), neurotrophin, and toll-like receptor (TLR) signaling, which are intimately associated with neuronal survival, immune response, and inflammation. Moreover, the molecular simulation study further verified that fucosterol exhibited a significant binding affinity to some of the vital targets, including liver X-receptor-beta (LXR-β), glucocorticoid receptor (GR), tropomyosin receptor kinase B (TrkB), toll-like receptor 2/4 (TLR2/4), and β-secretase (BACE1), which are the crucial regulators of molecular and cellular processes associated with NDD. Together, the present system pharmacology and in silico findings demonstrate that fucosterol might play a significant role in modulating NDD-pathobiology, supporting its therapeutic application for the prevention and treatment of NDD.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Deciphering Molecular Mechanism of the Neuropharmacological Action of Fucosterol through Integrated System Pharmacology and In Silico Analysis

et al. 2019

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“…In brief, fucosterol exhibited anti-inflammatory action [ 82 ] and attenuated LPS-induced inflammation in RAW 264.7 macrophage [ 72 ]; [ 83 ] and alveolar macrophage [ 84 ]. Fucosterol also protected against LPS- or Aβ-mediated neuroinflammation in activated microglial cells [ 85 ]. Several phlorotannins, such as dieckol [ 86 ], phlorofucofuroeckol A [ 87 ] and phlorofucofuroeckol B [ 88 ], 6,6’-bieckol [ 89 ], and 8,8’-bieckol [ 90 ] isolated from Ecklonia spp have been reported for their anti-inflammatory activities that involved suppression of NF-κB and MAPK pathways.…”

Section: Neuropharmacological Potentials Of Marine Algae and Theirmentioning

confidence: 99%

“…For example, fucosterol and 24-hydroperoxy 24-vinylcholesterol isolated from E. stolonifera showed inhibitory activity against butyrylcholinesterase (BChE) [ 114 ]. Another study also demonstrated anticholinesterase activity of fucosterol [ 85 ]. Enzyme kinetics and computational analysis indicated a non-competitive mode of acetylcholinesterase (AChE) inhibition of fucosterol [ 115 ].…”

Section: Neuropharmacological Potentials Of Marine Algae and Theirmentioning

confidence: 99%

Neuroprotective Potentials of Marine Algae and Their Bioactive Metabolites: Pharmacological Insights and Therapeutic Advances

et al. 2020

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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.

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“…Mounting evidence suggests anti-inflammatory potentials of marine sterols. Fucosterol treatment of lipopolysaccharide (LPS)- or Aβ-stimulated microglial cells ameliorated inflammation by lowering the secretion of IL-1β, IL-6, TNF-α, nitric oxide (NO), and PGE2 [ 24 ]. Fucosterol attenuated the inflammatory response in LPS-stimulated RAW 264.7 macrophages by downregulating COX-2 and iNOS expression and suppressing NF-κB signaling [ 21 ].…”

Section: Effects Of Marine Sterols Against Pathobiology Of Admentioning

confidence: 99%

Prospects of Marine Sterols against Pathobiology of Alzheimer’s Disease: Pharmacological Insights and Technological Advances

et al. 2021

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Alzheimer’s disease (AD) is a degenerative brain disorder characterized by a progressive decline in memory and cognition, mostly affecting the elderly. Numerous functional bioactives have been reported in marine organisms, and anti-Alzheimer’s agents derived from marine resources have gained attention as a promising approach to treat AD pathogenesis. Marine sterols have been investigated for several health benefits, including anti-cancer, anti-obesity, anti-diabetes, anti-aging, and anti-Alzheimer’s activities, owing to their anti-inflammatory and antioxidant properties. Marine sterols interact with various proteins and enzymes participating via diverse cellular systems such as apoptosis, the antioxidant defense system, immune response, and cholesterol homeostasis. Here, we briefly overview the potential of marine sterols against the pathology of AD and provide an insight into their pharmacological mechanisms. We also highlight technological advances that may lead to the potential application of marine sterols in the prevention and therapy of AD.

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Fucosterol inhibits the cholinesterase activities and reduces the release of pro-inflammatory mediators in lipopolysaccharide and amyloid-induced microglial cells

Cited by 32 publications

References 68 publications

Deciphering Molecular Mechanism of the Neuropharmacological Action of Fucosterol through Integrated System Pharmacology and In Silico Analysis

Deciphering Molecular Mechanism of the Neuropharmacological Action of Fucosterol through Integrated System Pharmacology and In Silico Analysis

Neuroprotective Potentials of Marine Algae and Their Bioactive Metabolites: Pharmacological Insights and Therapeutic Advances

Prospects of Marine Sterols against Pathobiology of Alzheimer’s Disease: Pharmacological Insights and Technological Advances

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