Ether Phosphatidylserine from Soft Coral Sclerophytum heterospiculatum Reveals Antioxidant Activity and Modulates Lipid Composition in LPS-Activated Human Microglial HMC-3 Cells.

Ether phospholipids from marine organisms represent an understudied class of bioactive lipids with unique structural features. In this study, we isolated, for the first time, an ether phosphatidylserine (ePS) species from the soft coral Sclerophytum heterospiculatum and assessed its biological activity on human microglial clone 3 (HMC-3) cells. The isolated ePS contained an ether bond at the sn-1 position and very-long-chain polyunsaturated fatty acids (PUFA) (24:5) at the sn-2 position. Using an MTS assay, we demonstrated that ePS was non-cytotoxic at all tested concentrations (0.39-100 μg/mL) and even increased microglial proliferation at 50-100 μg/mL. In microglial cells activated by lipopolysaccharide (LPS-activated), ePS significantly reduced production of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). A lipidomic analysis by HPLC-MS/MS revealed that ePS modulated the membrane lipid composition of microglial cells, increasing the content of polyunsaturated phosphatidylserines (PS 36:3, PS 40:5) and decreasing the levels of phosphatidylinositols (PI 18:1/20:4; PI 18:0/20:4, 18:1/20:3). Furthermore, a fatty acid analysis showed that ePS prevented LPS-induced accumulation of saturated fatty acids and preserved PUFA levels in HMC-3 cells. These findings suggest that marine-derived ePS can be considered as promising agents with antioxidant and anti-inflammatory properties.