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Antinociception produced by Thalassia testudinum extract BM-21 is mediated by the inhibition of acid sensing ionic channels by the phenolic compound thalassiolin B.

Garateix A, Salceda E, Menéndez R, Regalado EL, López O, García T, Morales RA, Laguna A, Thomas OP, Soto E - Mol Pain (2011)

Bottom Line: 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 antinociceptive effects of BM-21 and thalassiolin B may be partially because of this action on the ASICs.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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.

ABSTRACT

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.

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Effects of BM-21 on the thermal nociception and acetic acid writhing test. A) In the hot plate test the use of BM-21 (40 - 1000 mg kg-1) and 15 mg kg-1 indomethacin increased the latency of response measured 90 min after drug administration. Control = 3.3 s (dotted line). * P ≤ 0.05, ** P ≤ 0.001. In this and following graphs each bar represents mean ± SE, marks * and ** indicate significantly different from control (P ≤ 0.05, P ≤ 0.001) (one-way ANOVA and Student's t-tests). B) Number of contortions and stretches generated by the intraperitoneal injection of acetic acid measured in control and after 90 min of BM-21 or indomethacin administration.
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Figure 2: Effects of BM-21 on the thermal nociception and acetic acid writhing test. A) In the hot plate test the use of BM-21 (40 - 1000 mg kg-1) and 15 mg kg-1 indomethacin increased the latency of response measured 90 min after drug administration. Control = 3.3 s (dotted line). * P ≤ 0.05, ** P ≤ 0.001. In this and following graphs each bar represents mean ± SE, marks * and ** indicate significantly different from control (P ≤ 0.05, P ≤ 0.001) (one-way ANOVA and Student's t-tests). B) Number of contortions and stretches generated by the intraperitoneal injection of acetic acid measured in control and after 90 min of BM-21 or indomethacin administration.

Mentions: The BM-21 was used in concentrations ranging from 4 to 1000 mg kg-1 in the diverse models of nociception. In the hot plate test, the administration of 4 and 20 mg kg-1 BM-21 (n = 6 each) produced no significant effect. However BM-21 (40, 100, 400, and 1000 mg kg-1; n = 12 each) and indomethacin (15 mg kg-1; n = 16) produced a significant increase in the response latency tested 90 min after its administration (P ≤ 0.05; Figure 2A), although the action of 400 and 1000 mg.kg-1 BM-21 had a lower amplitude than that produced with 40 mg kg-1.


Antinociception produced by Thalassia testudinum extract BM-21 is mediated by the inhibition of acid sensing ionic channels by the phenolic compound thalassiolin B.

Garateix A, Salceda E, Menéndez R, Regalado EL, López O, García T, Morales RA, Laguna A, Thomas OP, Soto E - Mol Pain (2011)

Effects of BM-21 on the thermal nociception and acetic acid writhing test. A) In the hot plate test the use of BM-21 (40 - 1000 mg kg-1) and 15 mg kg-1 indomethacin increased the latency of response measured 90 min after drug administration. Control = 3.3 s (dotted line). * P ≤ 0.05, ** P ≤ 0.001. In this and following graphs each bar represents mean ± SE, marks * and ** indicate significantly different from control (P ≤ 0.05, P ≤ 0.001) (one-way ANOVA and Student's t-tests). B) Number of contortions and stretches generated by the intraperitoneal injection of acetic acid measured in control and after 90 min of BM-21 or indomethacin administration.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3037906&req=5

Figure 2: Effects of BM-21 on the thermal nociception and acetic acid writhing test. A) In the hot plate test the use of BM-21 (40 - 1000 mg kg-1) and 15 mg kg-1 indomethacin increased the latency of response measured 90 min after drug administration. Control = 3.3 s (dotted line). * P ≤ 0.05, ** P ≤ 0.001. In this and following graphs each bar represents mean ± SE, marks * and ** indicate significantly different from control (P ≤ 0.05, P ≤ 0.001) (one-way ANOVA and Student's t-tests). B) Number of contortions and stretches generated by the intraperitoneal injection of acetic acid measured in control and after 90 min of BM-21 or indomethacin administration.
Mentions: The BM-21 was used in concentrations ranging from 4 to 1000 mg kg-1 in the diverse models of nociception. In the hot plate test, the administration of 4 and 20 mg kg-1 BM-21 (n = 6 each) produced no significant effect. However BM-21 (40, 100, 400, and 1000 mg kg-1; n = 12 each) and indomethacin (15 mg kg-1; n = 16) produced a significant increase in the response latency tested 90 min after its administration (P ≤ 0.05; Figure 2A), although the action of 400 and 1000 mg.kg-1 BM-21 had a lower amplitude than that produced with 40 mg kg-1.

Bottom Line: 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 antinociceptive effects of BM-21 and thalassiolin B may be partially because of this action on the ASICs.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus