Soy lysolecithin attenuates hypertension and behavioral impairments in mice fed a high-salt diet through receptor-specific regulation of prostaglandin signaling and arachidonic acid-derived prostaglandin production.

High salt (HS) intake is a major risk factor of hypertension and has been implicated in emotional and cognitive decline. On the other hand, dietary supplementation may represent a potential preventive strategy against health risks induced by HS intake. Soybean lecithin is widely used as a phospholipid supplement. Here, we investigated the effects of lysolecithin enriched in lysophosphatidylcholine (>70% of total phospholipids; LPC70) on hypertension and behavioral impairments under high-salt diet (HSD) conditions in mice. To further characterize these effects, we examined changes in prostaglandin (PG)-related pathways by integrating gene expression and lipidomic analyses. Mice were fed an HSD (chow containing 8% NaCl) with or without LPC70 for 10 weeks. HSD elevated systolic blood pressure and impaired social behavior and object recognition memory in mice. Quantitative gene expression analyses revealed that HSD increased renal expression of cyclooxygenase-2 (COX-2) and EP3 (PGE2 receptor), and reduced expression of DP1 (PGD2 receptor) in the prefrontal cortex. LPC70 attenuated these changes in behavior, blood pressure, and PG-related gene expression. Furthermore, lipidomic analyses revealed that HSD reduced circulating arachidonic acid (AA) levels, whereas LPC70 increased AA-derived PG, such as PGE2 and PGD2, in HSD-fed mice. These findings demonstrate that LPC70 may protect against hypertension and behavioral impairments under HSD conditions in mice, potentially in association with modulation of PG signaling. LPC70 may serve as a functional dietary component that reshapes lipid mediator signaling under HSD conditions.