title: Isolation of a diterpenoid substance with potent neuroprotective activity from fetal calf serum.
abstract: Excess activation of glutamate receptors and production of free radicals including nitric oxide may result in severe and irreversible damage to the mammalian central nervous system (CNS), but endogenous defense systems that protect neurons from these insults are poorly understood. Here, we purified and isolated a neuroprotective substance, which has been named "serofendic acid," from a lipophilic fraction of FCS based on the ability to protect rat primary cortical neurons against nitric oxide cytotoxicity. Mass spectrometry and NMR spectroscopy revealed the chemical structure of serofendic acid (15-hydroxy-17-methylsulfinylatisan-19-oic acid) as a sulfur-containing atisane-type diterpenoid, which is unique among known endogenous substances. Synthetic serofendic acid exhibited potent protective actions on cortical neurons against cytotoxicity of a nitric oxide donor as well as of glutamate, although it did not show appreciable influences on glutamate receptor-mediated responses in these neurons. Electron spin resonance analysis demonstrated that serofendic acid had no direct scavenging activity on nitric oxide radicals but was capable of inhibiting the generation of hydroxyl radical, a presumed "executor" radical in the nitric oxide-mediated neurotoxic cascade. These findings suggest that serofendic acid is a low-molecular-weight bioactive factor that promotes survival of CNS neurons, probably through the attenuation of free radical-mediated insults.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kume
authors.forename: Naoki
authors.initials: N
authors.lastname: Asai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Nariyasu
authors.initials: N
authors.lastname: Mano
authors.forename: Taro
authors.initials: T
authors.lastname: Terauchi
authors.forename: Ryota
authors.initials: R
authors.lastname: Taguchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Shirakawa
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Osakada
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mori
authors.forename: Naoki
authors.initials: N
authors.lastname: Asakawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yonaga
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Hachiro
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katsuki
authors.forename: Shuji
authors.initials: S
authors.lastname: Kaneko
authors.forename: Akinori
authors.initials: A
authors.lastname: Akaike
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats
chemical_list: D004224:Diterpenes; D018696:Neuroprotective Agents; C452642:serofendic acid