Identification of a novel natural compound that acts on the membrane progestin receptor α (paqr7) from the marine algae Padina

Previously, we identified water-soluble compounds with membrane progestin receptor α (mPRα)-binding activity from the marine algae Padina arborescens. The compounds inhibited fish oocyte maturation. These compounds are potentially novel antagonists of mPR and are of interest as novel inhibitors of the nongenomic pathway of steroids. In this study, a compound with mPRα binding activity was purified from the methanol extract of Padina tarries. The structure of one of the major compounds in the fraction was identified as 1-carboxybutyl-2-hydroxypentanoate (1-CB 2-HPNA) using nuclear magnetic resonance spectroscopy and ESI-MS analysis. 1-CB 2-HPNA showed substantial competitive binding affinity for human mPRα (hmPRα) in the graphene quantum dot (GQD)-hmPRα binding assay. The physiological activity of 1-CB 2-HPNA was then evaluated using an in vitro and in vivo zebrafish oocyte maturation and ovulation assay. 1-CB 2-HPNA inhibited the maturation and ovulation of fish oocytes. In addition, 1-CB 2-HPNA inhibited ovulation in mice. These results indicate that 1-CB 2-HPNA, identified from Padina arborescens, is a novel natural mPRα antagonist.