A brown seaweed Sargassum fusiforme polysaccharides protect against ischemic stroke by mediating angiogenic factors through the modulation of the HIF-1α/VEGF pathway

Abstract

Ischemic stroke (IS) has emerged as one of the leading causes of mortality and disability in adults worldwide. Hypoxia-inducible factor 1α (HIF-1α) signaling pathway plays a critical role in endogenous neuroprotective mechanisms following IS. Sargassum fusiforme is a significant marine algal resource. In previous research, we isolated bioactive fucoidan from acid-processed S. fusiforme, and demonstrated its anti-inflammatory and antioxidant efficacy. This study aimed to elucidate the role of S. fusiforme polysaccharides (SFPS) in promoting angiogenesis via the HIF 1α/vascular endothelial growth factor (VEGF) pathway following IS and to investigate the underlying mechanisms involved. In this study, we employed a hypoxia model in human cerebral microvascular endothelial cells (hCMECs/ D3) and a zebrafish IS model to elucidate the therapeutic mechanisms of SFPS in mitigating cerebral ischemic injury. Cellular assays confirmed the ability of fucoidan to prevent apoptosis and promote neovascularization in hCMEC/D3 cells under hypoxic stress. Furthermore, in a zebrafish IS model, fucoidan increased blood flow velocity and locomotor activity, while reducing neuronal apoptosis. Mechanistically, fucoidan activated the HIF-1α/VEGF signaling pathway in both cellular and animal models, thereby ameliorating hypoxic injury and stimulating angiogenesis. Results demonstrated the angiogenic activity of fucoidan in both in vitro and in vivo models, and revealed its key targets and associated pathways underlying its anti-ischemic effects. Findings collectively highlight the prospective utility of fucoidan as a marine-derived therapeutic agent from traditional Chinese medicine for neurovascular repair.

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