Antinociception Produced by Thalassia Testudinum Extract BM-21 is Mediated by the Inhibition of Acid Sensing Ionic Channels by the Phenolic Compound Thalassiolin B

Abstract

BackgroundAcid-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.ResultsBehavioral 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.ConclusionsTo 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.

Lignan from Thyme Possesses Inhibitory Effect on ASIC3 Channel Current

“…In the same manner, a polypeptide toxin APETx2 specifically inhibits transient ASIC3 currents with IC 50 63 nM, without affecting sustained ASIC3 currents (32). Another natural component, thalassiolin B, from the extract of sea grass Thalassia testudinum shows small inhibitory effects of about 30% only on the transient currents (IC 50 27 M), but produces significant antinociceptive effects (33). Other non-peptide compounds such as salicylic acid (IC 50 260 M) or diclofenac (IC 50 92 M) inhibit the sustained component of the ASIC3 current, but not the transient component (21).…”

Modulation of biotransformation and elimination systems by BM-21, an aqueous ethanolic extract from Thalassia testudinum, and thalassiolin B on human hepatocytes

“…Phenols are the main fraction and thalassiolin B (TB) (Fig. 1) is the most abundant component (Garateix et al, 2011;Regalado et al, 2009).…”

“…Cytoprotective effects of BM-21 are likely related to its antioxidative properties. In addition, in vitro and in vivo neuroprotective effects have recently been reported, which could represent potential applications of the extract as medicine food (Garateix et al, 2011).…”

STUDY OF THE INTERACTION OF AN EXTRACT OBTAINED FROM THE MARINE PLANT Thalassia testudinum WITH PHASE I METABOLISM IN RATS

“…The results were: total phenolic content (29.5 ± 1.2 %), flavonoids (4.6 ± 0.2 %), proanthocyanidins (21.0 ± 2.3 %), polysaccharides (5.8 ± 1.6 %), lipids (0.59 ± 0.01 %), soluble proteins (16.2 ± 0.7 %) and chlorophylls a and b (3.43 and 1.44 μg/mL, respectively) . Thalassiolin B (5.8 ± 0.9 %) was quantified as reported previously (Garateix et al 2011). Details are available as supplementary data on Regalado et al (2012).…”

“…The pharmacological properties of the extract include anti-inflammatory and antioxidant effects (Nuñez et al 2006, Rodeiro et al 2008a. Neuroprotective properties have also been reported in rodents, which may represent a therapeutic application of the extract (Garateix et al 2011, Menendez et al 2014). Due to these beneficial effects, a food supplement is being developed from the extract.…”