Antinociception produced by Thalassia testudinum extract BM-21 is mediated by the inhibition of acid sensing ionic channels by the phenolic compound thalassiolin B.
BACKGROUND
Acid-sensing ion channels (ASICs) have a significant role in the sensation of pain and constitute an important target for the search of new antinociceptive drugs. In this work we studied the antinociceptive properties of the BM-21 extract, obtained from the sea grass Thalassia testudinum, in chemical and thermal models of nociception in mice. The action of the BM-21 extract and the major phenolic component isolated from this extract, a sulphated flavone glycoside named thalassiolin B, was studied in the chemical nociception test and in the ASIC currents of the dorsal root ganglion (DRG) neurons obtained from Wistar rats.


RESULTS
Behavioral antinociceptive experiments were made on male OF-1 mice. Single oral administration of BM-21 produced a significant inhibition of chemical nociception caused by acetic acid and formalin (specifically during its second phase), and increased the reaction time in the hot plate test. Thalassiolin B reduced the licking behavior during both the phasic and tonic phases in the formalin test. It was also found that BM-21 and thalassiolin B selectively inhibited the fast desensitizing (τ < 400 ms) ASIC currents in DRG neurons obtained from Wistar rats, with a nonsignificant action on ASIC currents with a slow desensitizing time-course. The action of thalassiolin B shows no pH or voltage dependence nor is it modified by steady-state ASIC desensitization or voltage. The high concentration of thalassiolin B in the extract may account for the antinociceptive action of BM-21.


CONCLUSIONS
To our knowledge, this is the first report of an ASIC-current inhibitor derived of a marine-plant extract, and in a phenolic compound. The antinociceptive effects of BM-21 and thalassiolin B may be partially because of this action on the ASICs. That the active components of the extract are able to cross the blood-brain barrier gives them an additional advantage for future uses as tools to study pain mechanisms with a potential therapeutic application.
Centro de Bioproductos Marinos, Agencia de Medio Ambiente, Ministerio de Ciencia, Tecnología y Medio Ambiente, Loma y 37, Alturas del Vedado, CP 10600 La Habana, Cuba.
Anoland
A
Garateix
Emilio
E
Salceda
Roberto
R
Menéndez
Erik L
EL
Regalado
Omar
O
López
Teidy
T
García
Ruth A
RA
Morales
Abilio
A
Laguna
Olivier P
OP
Thomas
Enrique
E
Soto
D062565:Acid Sensing Ion Channels; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D045424:Complex Mixtures; D005419:Flavonoids / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D031321:Hydrocharitaceae / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D010147:Pain Measurement; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011522:Protons; D051381:Rats; D045442:Rotarod Performance Test; D015222:Sodium Channels / Q000378:metabolism; D013696:Temperature
D062565:Acid Sensing Ion Channels; D045424:Complex Mixtures; D005419:Flavonoids; D009419:Nerve Tissue Proteins; D010636:Phenols; D010936:Plant Extracts; D011522:Protons; D015222:Sodium Channels; C471629:thalassiolin B; D000584:Amiloride
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