title: Lignan from thyme possesses inhibitory effect on ASIC3 channel current.
abstract: A novel compound was identified in the acidic extract of Thymus armeniacus collected in the Lake Sevan region of Armenia. This compound, named "sevanol," to our knowledge is the first low molecular weight natural molecule that has a reversible inhibition effect on both the transient and the sustained current of human ASIC3 channels expressed in Xenopus laevis oocytes. Sevanol completely blocked the transient component (IC(50) 353 ± 23 μM) and partially (∼45%) inhibited the amplitude of the sustained component (IC(50) of 234 ± 53 μM). Other types of acid-sensing ion channel (ASIC) channels were intact to sevanol application, except ASIC1a, which showed more than six times less affinity to it as compared with the inhibitory action on the ASIC3 channel. To elucidate the structure of sevanol, the set of NMR spectra in two solvents (d(6)-DMSO and D(2)O) was collected, and the complete chemical structure was confirmed by liquid chromatography-mass spectrometry with electrospray ionization (LC-ESI(+)-MS) fragmentation. This compound is a new lignan built up of epiphyllic acid and two isocitryl esters in positions 9 and 10. In vivo administration of sevanol (1-10 mg/kg) significantly reversed thermal hyperalgesia induced by complete Freund's adjuvant injection and reduced response to acid in a writhing test. Thus, we assume the probable considerable role of sevanol in known analgesic and anti-inflammatory properties of thyme.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya Street, 117997 Moscow, Russian Federation. maxim@nmr.ru
authors.forename: Maxim A
authors.initials: MA
authors.lastname: Dubinnyi
authors.forename: Dmitry I
authors.initials: DI
authors.lastname: Osmakov
authors.forename: Sergey G
authors.initials: SG
authors.lastname: Koshelev
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Kozlov
authors.forename: Yaroslav A
authors.initials: YA
authors.lastname: Andreev
authors.forename: Naira A
authors.initials: NA
authors.lastname: Zakaryan
authors.forename: Igor A
authors.initials: IA
authors.lastname: Dyachenko
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Bondarenko
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Arseniev
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Grishin
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D046930:Thymus Plant / Q000737:chemistry*; D014982:Xenopus laevis
chemical_list: C568266:ASIC1 protein, human; C112231:ASIC3 protein, human; D062565:Acid Sensing Ion Channels; D000894:Anti-Inflammatory Agents, Non-Steroidal; D017705:Lignans