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Modulation of TRP channels by resveratrol and other stilbenoids.

Yu L, Wang S, Kogure Y, Yamamoto S, Noguchi K, Dai Y - Mol Pain (2013)

Bottom Line: Otherwise, trans-stilbene showed no any effect on I AITC or I CAP.By contrast, the inhibition of TRPV1 by PME did not change the capsaicin-induced maximum response but did cause a right shift of the EC50.These data suggest that resveratrol and other stilbenoids may have an inhibitory effect on TRP channels.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530, Japan.

ABSTRACT

Background: Resveratrol (3,5,4' - trihydroxy-trans-stilbene), a widely distributed natural stilbenoid, was proposed to account for the unique effects of red wine on life span and health. It has been reported to possess various biological and pharmacological activities, such as anti-oxidant, anti-inflammatory, and anti-carcinogenic effects. Here, using whole-cell patch-clamp techniques and behavioral analyses, we investigated whether resveratrol and other stilbenoids can modulate TRP channels in sensory neurons in vitro, and have analgesic effects in vivo.

Results: We found that resveratrol dose-dependently suppressed the allyl isothiocyanate (AITC)-induced currents (I AITC) in HEK293 cells that express TRPA1, as well as in rat dorsal root ganglion (DRG) neurons. Instead, pinosylvin methyl ether (PME), another derivate of stilbene which has a similar structure to resveratrol, dose-dependently blocked the capsaicin-induced currents (I CAP) in HEK293 cells that express TRPV1 as well as in DRG neurons. Interestingly, resveratrol had no inhibitory effect on the I CAP, and PME had no effect on the I AITC. Otherwise, trans-stilbene showed no any effect on I AITC or I CAP. The concentration response curve of AITC showed that resveratrol inhibited the action of TRPA1 not by changing the EC50, but by suppressing the AITC-induced maximum response. By contrast, the inhibition of TRPV1 by PME did not change the capsaicin-induced maximum response but did cause a right shift of the EC50. Moreover, pre-administration of resveratrol suppressed intraplantar injections of AITC-evoked nocifensive behaviors, as well as that PME suppressed capsaicin-evoked one.

Conclusions: These data suggest that resveratrol and other stilbenoids may have an inhibitory effect on TRP channels. In addition, these stilbenoids modulate TRP channel activity in different ways.

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Resveratrol but not PME inhibits AITC-induced pain behavior. Resveratrol (RES, 300 μM, 50 μl) or PME (300 μM, 50 μl) was pre-treated subcutaneously 5 min before AITC (3% in 50 μl liquid paraffin) or vehicle (VEH) injection. A, C: Time course of the number of paw flinches (A) or duration of paw licks (C) induced by AITC or VEH after resveratrol or PME pretreatment, respectively. The number of flinches and duration of licks were counted per 5 min interval in the initial 30 min period after AITC injection. * p < 0.05, ** p < 0.01, versus VEH + AITC (one-way ANOVA followed by Fisher’s PLSD); # p < 0.05, versus VEH + AITC group (two-way repeated ANOVA followed by Fisher’s PLSD). B, D: Cumulative number of paw flinches (B) or duration of paw licks (D) in the initial 30 min period after AITC - or VEH - injection. $ p < 0.05, versus VEH + AITC, (one way ANOVA followed by Fisher’s PLSD). Numbers in parentheses indicate number of rats used in each group.
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Figure 7: Resveratrol but not PME inhibits AITC-induced pain behavior. Resveratrol (RES, 300 μM, 50 μl) or PME (300 μM, 50 μl) was pre-treated subcutaneously 5 min before AITC (3% in 50 μl liquid paraffin) or vehicle (VEH) injection. A, C: Time course of the number of paw flinches (A) or duration of paw licks (C) induced by AITC or VEH after resveratrol or PME pretreatment, respectively. The number of flinches and duration of licks were counted per 5 min interval in the initial 30 min period after AITC injection. * p < 0.05, ** p < 0.01, versus VEH + AITC (one-way ANOVA followed by Fisher’s PLSD); # p < 0.05, versus VEH + AITC group (two-way repeated ANOVA followed by Fisher’s PLSD). B, D: Cumulative number of paw flinches (B) or duration of paw licks (D) in the initial 30 min period after AITC - or VEH - injection. $ p < 0.05, versus VEH + AITC, (one way ANOVA followed by Fisher’s PLSD). Numbers in parentheses indicate number of rats used in each group.

Mentions: Then we tested the effects of pretreatment resveratrol or PME on AITC- or capsaicin-induced behaviors. We found these two derivatives of stilbene did not cause any inflammatory reactions (e.g. redness, swelling) or acute nocifensive behavior (e.g. paw lifting, flinching or licking). After pre-treatment with resveratrol (300 μM) or PME (300 μM), AITC or capsaicin was injected into the same area of the hind paw, as previously described [30,31]. Pre-treatment with resveratrol significantly decreased the number of paw flinches induced by AITC (but not capsaicin) from 15 min post-injection period in a continuously gradual manner (Figure 7A, B). Pre-treatment with PME also significantly decreased the number of paw flinches induced by capsaicin (but not AITC) injection (Figure 8A, B). However, the AITC- or capsaicin-induced paw licks were not significantly changed by pretreatment of either resveratrol or PME, respectively (Figure 7C, D and Figure 8C, D).


Modulation of TRP channels by resveratrol and other stilbenoids.

Yu L, Wang S, Kogure Y, Yamamoto S, Noguchi K, Dai Y - Mol Pain (2013)

Resveratrol but not PME inhibits AITC-induced pain behavior. Resveratrol (RES, 300 μM, 50 μl) or PME (300 μM, 50 μl) was pre-treated subcutaneously 5 min before AITC (3% in 50 μl liquid paraffin) or vehicle (VEH) injection. A, C: Time course of the number of paw flinches (A) or duration of paw licks (C) induced by AITC or VEH after resveratrol or PME pretreatment, respectively. The number of flinches and duration of licks were counted per 5 min interval in the initial 30 min period after AITC injection. * p < 0.05, ** p < 0.01, versus VEH + AITC (one-way ANOVA followed by Fisher’s PLSD); # p < 0.05, versus VEH + AITC group (two-way repeated ANOVA followed by Fisher’s PLSD). B, D: Cumulative number of paw flinches (B) or duration of paw licks (D) in the initial 30 min period after AITC - or VEH - injection. $ p < 0.05, versus VEH + AITC, (one way ANOVA followed by Fisher’s PLSD). Numbers in parentheses indicate number of rats used in each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585750&req=5

Figure 7: Resveratrol but not PME inhibits AITC-induced pain behavior. Resveratrol (RES, 300 μM, 50 μl) or PME (300 μM, 50 μl) was pre-treated subcutaneously 5 min before AITC (3% in 50 μl liquid paraffin) or vehicle (VEH) injection. A, C: Time course of the number of paw flinches (A) or duration of paw licks (C) induced by AITC or VEH after resveratrol or PME pretreatment, respectively. The number of flinches and duration of licks were counted per 5 min interval in the initial 30 min period after AITC injection. * p < 0.05, ** p < 0.01, versus VEH + AITC (one-way ANOVA followed by Fisher’s PLSD); # p < 0.05, versus VEH + AITC group (two-way repeated ANOVA followed by Fisher’s PLSD). B, D: Cumulative number of paw flinches (B) or duration of paw licks (D) in the initial 30 min period after AITC - or VEH - injection. $ p < 0.05, versus VEH + AITC, (one way ANOVA followed by Fisher’s PLSD). Numbers in parentheses indicate number of rats used in each group.
Mentions: Then we tested the effects of pretreatment resveratrol or PME on AITC- or capsaicin-induced behaviors. We found these two derivatives of stilbene did not cause any inflammatory reactions (e.g. redness, swelling) or acute nocifensive behavior (e.g. paw lifting, flinching or licking). After pre-treatment with resveratrol (300 μM) or PME (300 μM), AITC or capsaicin was injected into the same area of the hind paw, as previously described [30,31]. Pre-treatment with resveratrol significantly decreased the number of paw flinches induced by AITC (but not capsaicin) from 15 min post-injection period in a continuously gradual manner (Figure 7A, B). Pre-treatment with PME also significantly decreased the number of paw flinches induced by capsaicin (but not AITC) injection (Figure 8A, B). However, the AITC- or capsaicin-induced paw licks were not significantly changed by pretreatment of either resveratrol or PME, respectively (Figure 7C, D and Figure 8C, D).

Bottom Line: Otherwise, trans-stilbene showed no any effect on I AITC or I CAP.By contrast, the inhibition of TRPV1 by PME did not change the capsaicin-induced maximum response but did cause a right shift of the EC50.These data suggest that resveratrol and other stilbenoids may have an inhibitory effect on TRP channels.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530, Japan.

ABSTRACT

Background: Resveratrol (3,5,4' - trihydroxy-trans-stilbene), a widely distributed natural stilbenoid, was proposed to account for the unique effects of red wine on life span and health. It has been reported to possess various biological and pharmacological activities, such as anti-oxidant, anti-inflammatory, and anti-carcinogenic effects. Here, using whole-cell patch-clamp techniques and behavioral analyses, we investigated whether resveratrol and other stilbenoids can modulate TRP channels in sensory neurons in vitro, and have analgesic effects in vivo.

Results: We found that resveratrol dose-dependently suppressed the allyl isothiocyanate (AITC)-induced currents (I AITC) in HEK293 cells that express TRPA1, as well as in rat dorsal root ganglion (DRG) neurons. Instead, pinosylvin methyl ether (PME), another derivate of stilbene which has a similar structure to resveratrol, dose-dependently blocked the capsaicin-induced currents (I CAP) in HEK293 cells that express TRPV1 as well as in DRG neurons. Interestingly, resveratrol had no inhibitory effect on the I CAP, and PME had no effect on the I AITC. Otherwise, trans-stilbene showed no any effect on I AITC or I CAP. The concentration response curve of AITC showed that resveratrol inhibited the action of TRPA1 not by changing the EC50, but by suppressing the AITC-induced maximum response. By contrast, the inhibition of TRPV1 by PME did not change the capsaicin-induced maximum response but did cause a right shift of the EC50. Moreover, pre-administration of resveratrol suppressed intraplantar injections of AITC-evoked nocifensive behaviors, as well as that PME suppressed capsaicin-evoked one.

Conclusions: These data suggest that resveratrol and other stilbenoids may have an inhibitory effect on TRP channels. In addition, these stilbenoids modulate TRP channel activity in different ways.

Show MeSH
Related in: MedlinePlus