title: Mechanism of action of antiepileptic ceramide from Red Sea soft  coral Sarcophyton auritum.
abstract: Chemical investigation of the Red Sea soft coral Sarcophyton auritum led to the isolation and structure elucidation of a new ceramide N-((2S,3R,4E,6E)-1,3-dihydroxyhenicosa-4,6-dien-2-yl)tridecanamide (1). Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The anticonvulsant activity of the isolated ceramide was measured in vivo using the pentylenetetrazole (PTZ)-induced seizure model, where it successfully antagonized the lethality of pentylenetetrazole in mice. In addition, the isolated ceramide showed good anxiolytic activity when used in the light–dark transition box and the elevated plus maze compared to diazepam. The molecular modeling studies for the antiepileptic and antianxiety mechanism of the isolated ceramide suggested a CNS depressing activity possibly through GABA and serotonin receptors modulation. The pharmacological activity of the ceramide involved agonistic activity on GABA-A receptors but not 5HT3 receptors.
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
authors.forename: Nermeen A
authors.initials: NA
authors.lastname: Eltahawy
authors.forename: Amany K
authors.initials: AK
authors.lastname: Ibrahim
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Radwan
authors.forename: Sawsan A
authors.initials: SA
authors.lastname: Zaitone
authors.forename: Mohamed
authors.initials: M
authors.lastname: Gomaa
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: ElSohly
authors.forename: Hashim A
authors.initials: HA
authors.lastname: Hassanean
authors.forename: Safwat A
authors.initials: SA
authors.lastname: Ahmed
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D037421:Anthozoa / Q000737:chemistry* / Q000378:metabolism; D000927:Anticonvulsants / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use; D001665:Binding Sites; D002518:Ceramides / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use; D004195:Disease Models, Animal; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D018782:Maze Learning; D051379:Mice; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D010433:Pentylenetetrazole / Q000633:toxicity; D017434:Protein Structure, Tertiary; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D055672:Static Electricity
chemical_list: D000927:Anticonvulsants; D002518:Ceramides; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; C000610148:ceramide N-((2S,3R,4E,6E)-1,3-dihydroxyhenicosa-4,6-dien-2-yl)tridecanamide; D010433:Pentylenetetrazole