Gallic acid functions as a TRPA1 antagonist with relevant antinociceptive and antiedematogenic effects in mice

Abstract

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.

Oral Administration of the Japanese Traditional Medicine Keishibukuryogan-ka-yokuinin Decreases Reactive Oxygen Metabolites in Rat Plasma: Identification of Chemical Constituents Contributing to Antioxidant Activity

“…The following compounds were also identified in plasma at relatively-high concentrations; tumulosic acid, paeoniflorin, 4- O -methylgallic acid, gallic acid, manderonitrile, and ( E )-cinnamic acid. These constituents have been reported to have various pharmacological effects in cell culture systems and animal models focusing on dermatitis and blood flow [ 17 , 18 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

Methanolic Extract of Clinacanthus nutans Exerts Antinociceptive Activity via the Opioid/Nitric Oxide‐Mediated, but cGMP‐Independent, Pathways

“…Although MECN as a crude extract contains various types of bioactive compounds, flavonoid-based compounds, in part, have been reported to demonstrate antinociceptive activity. Of those detected compounds, at least gallic acid [ 35 ], caffeic acid [ 36 ], ferulic acid [ 37 ], vitexin [ 38 ], and apigenin [ 39 ] have been reported to exert antinociceptive activity when given orally. These compounds are suggested to work synergistically to exert the observed antinociceptive activity in MECN.…”

Cyclophosphamide-induced hepatotoxicity in wistar rats: The modulatory role of gallic acid as a hepatoprotective and chemopreventive phytochemical

“…GA an endogenous plant phenol is known to have antioxidant, anti-cancer, anti-inflammatory, neuroprotective, and free radical scavenging activity. [ 12 32 33 34 35 36 37 38 ]…”