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Stroke is the second leading cause of death and a major cause of disability worldwide. Ischemic stroke accounts for approximately &gt;60% of all stroke, and &gt;80% of strokes can be prevented. Middle cerebral artery occlusion (MCAO) is a common cause of stroke in humans. MCAO is associated with blood vessel-related problems, such as reduced vascular plasticity and hypertension. These problems can be attenuated by the use of nutraceuticals such as laminarin. Laminarin is a storage glucan commonly found in brown algae. Accumulating evidence and studies have revealed that laminarin is a promising candidate drug for treating ischaemic stroke. However, details on pharmaceutical targets and molecular mechanisms underlying laminarin’s beneficial effects for treating ischaemic stroke remains largely unknown. Herein, we applied network pharmacology, bioinformatic analysis, and middle cerebral artery occlusion model to delineate the protective role of laminarin. By comparing the laminarin- and MCAO-associated genes, we identified 23 potential targets including tumour necrosis factor (TNF), vascular endothelial growth factor A, selectin P, presenilin 1, fibroblast growth factor 2, microtubule-associated protein tau, caspase 3, matrix metallopeptidase 1, 5-hydroxytryptamine receptor 2A, telomerase reverse transcriptase, interleukin 2, signal transducer and activator of transcription 3 (STAT3), ATP binding cassette subfamily B member 1, catalase, superoxide dismutase 2, adenosine A1 receptor, adenosine A2a receptor, 5-hydroxytryptamine receptor 1B, heat shock protein 90 alpha family class A member 1, matrix metallopeptidase 8, BCL2-like 1, galectin 3, and epoxide hydrolase 2 of laminarin against ischaemic stroke. The gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses highlighted the importance of this gene cluster in the development of blood vessels, neuronal cell death, brain functions, and neuroinflammation. Furthermore, molecular docking analysis suggested a direct binding of laminarin to its target proteins STAT3 and TNF. Our results provide the pharmaceutical targets and delineate the details regarding the molecular mechanisms underlying the beneficial effects of laminarin against ischaemic stroke. Moreover, our findings support those of previous studies suggesting laminarin as a promising drug for treating ischaemic stroke.

Molecular mechanisms and biomarkers underlying the protective roles of the nutraceutical laminarin against ischaemic strokes