| Summary: | Marine cyanobacteria represent a large untapped source of functional glycolipids enriched with polyunsaturated fatty acids (PUFAs) for human health. However, advanced methods for scalable isolation of diverse species containing high-purity PUFA-rich glycolipids will have to be developed and their possible pharmaceutical and nutraceutical functions identified. This paper introduces a novel solid matrix-supported supercritical CO<sub>2</sub> extraction method for scalable isolation of the PUFA γ-linolenic acid (GLA)-enriched glycolipids from the cyanobacterium <i>Arthrospira</i> (<i>Spirulina</i>) <i>platensis</i>, which has been the most widely used among microalgae in the nutraceutical and pharmaceutical industries. Of various porous materials studied, diatomite was the best to facilitate extraction of GLA-rich glycolipids, resulting in an extraction efficiency of 98%. Gamma-linolenic acid made up 35% of total fatty acids (TFAs) in the extracts, which was considerably greater than that obtained with ethanol (26%), Bligh and Dyer (24%), and in situ transesterification (24%) methods, respectively. Lipidomics analysis revealed that GLA was exclusively associated with galactolipids. Pharmaceutical functions of GLA-rich galactolipids were investigated on a zebrafish caudal fin regeneration model. The results suggested that GLA extracted from <i>A. platensis</i> possessed anti-oxidative, anti-inflammatory, and anti-allergic activities, which acted in a concerted manner to promote post-injury regeneration of zebrafish.
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