Gallic acid functions as a TRPA1 antagonist with relevant antinociceptive and antiedematogenic effects in mice.
The transient receptor potential ankyrin 1 (TRPA1) has been identified as a relevant target for the development of novel analgesics. Gallic acid (GA) is a polyphenolic compound commonly found in green tea and various berries and possesses a wide range of biological activities. The goal of this study was to identify GA as a TRPA1 antagonist and observe its antinociceptive effects in different pain models. First, we evaluated the ability of GA to affect cinnamaldehyde-induced calcium influx. Then, we observed the antinociceptive and antiedematogenic effects of GA (3-100 mg/kg) oral administration after the intraplantar (i.pl.) injection of TRPA1 agonists (allyl isothiocyanate, cinnamaldehyde, or hydrogen peroxide-H2O2) in either an inflammatory pain model (carrageenan i.pl. injection) or a neuropathic pain model (chronic constriction injury) in male Swiss mice (25-35 g). GA reduced the calcium influx mediated by TRPA1 activation. Moreover, the oral administration of GA decreased the spontaneous nociception triggered by allyl isothiocyanate, cinnamaldehyde, and H2O2. Carrageenan-induced allodynia and edema were largely reduced by the pretreatment with GA. Moreover, the administration of GA was also capable of decreasing cold and mechanical allodynia in a neuropathic pain model. Finally, GA was absorbed after oral administration and did not produce any detectable side effects. In conclusion, we found that GA is a TRPA1 antagonist with antinociceptive properties in relevant models of clinical pain without detectable side effects, which makes it a good candidate for the treatment of painful conditions.
Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Chemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Avenida Roraima, 1000, Camobi, Santa Maria-RS, 97105-900, Brazil, gabitrev@hotmail.com.
Gabriela
G
Trevisan
Mateus F
MF
Rossato
Raquel
R
Tonello
Carin
C
Hoffmeister
Jonatas Z
JZ
Klafke
Fernanda
F
Rosa
Kelly V
KV
Pinheiro
Francielle V
FV
Pinheiro
Aline A
AA
Boligon
Margareth L
ML
Athayde
Juliano
J
Ferreira
D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D000700:Analgesics / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D005707:Gallic Acid / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006861:Hydrogen Peroxide; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D005707:Gallic Acid; D000171:Acrolein; D006861:Hydrogen Peroxide; C012843:cinnamaldehyde