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Life sciences · Journal article
Journal of Natural Products · October 9, 2026
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Abstract The rising prevalence of obesity calls for the development of novel treatments. Spirulina is known for its beneficial effects on metabolic health; however, the specific bioactive compounds have not yet been identified. This work aims to address this gap through the bioassay-guided isolation of lipid-reducing compounds from Limnospira platensis using zebrafish larvae. The primary bioactive compounds identified were the stereoisomers of 132-hydroxypheophytin a (132-hpa), with 132-(R)-hpa (2) (EC50 = 1.7 μM) that showed seven times higher lipid-reducing potential than 132-(S)-hpa (1) (EC50 = 11.7 μM). Both isomers prevented lipid accumulation in an in vitro steatosis model using oleic acid-overloaded HepG2 cells, and both remediated steatosis following prior lipid accumulation. Both compounds reduced Paramecia intake with similar EC50 values, but only 132-(S)-hpa (1) suppressed liposome intake (EC50 = 22.5 μM), which indicates different mechanisms of appetite regulation. No effects were observed on tissue glucose uptake or β-cell regeneration after ablation. Together, these findings identify the isomers of 132-hpa (1 and 2) as the principal bioactive compounds of spirulina, with differing lipid reduction potencies and appetite suppression, underscoring the importance of C-132 configuration for biological activity.