The semi-synthetic molecule [4″,5″] dihydro-obovatin isolated from Tephrosia Toxicaria pers reduces zymosan-induced temporomandibular joint inflammatory hypernociception in rats

Arthritis possesses inflammatory components and flavonoids of well-known structures exert anti-inflammatory activity. Here, we aim to evaluate the effects of [4″,5″] dihydro-obovatin and three structurally-defined flavonoids from Tephrosia toxicaria Pers roots on the zymosan-induced temporomandibular joint inflammatory hypernociception in rats as well as their toxicity. Rats were pretreated with the flavonoids (1 and 10 mg/kg) and [4″,5″] dihydro-obovatin (0.1 and 1.0 mg/kg) 1 h before intra-articular zymosan injection (2 mg, 40 μL). Von Frey test was used to evaluate the nociceptive threshold at the 4th hour after zymosan injection. Six hours after zymosan injection, synovial lavage was collected for total cell counting. Acute toxicity assay for [4″,5″] dihydro-obovatin (1, 10, and 100 mg/kg) were performed along with the subchronic toxicity assay by administering [4″,5″] dihydro-obovatin (0.01 mg/kg) or saline solution for 14 consecutive days and the rota-rod test was carried out to determine whether [4″,5″] dihydro-obovatin would impair motor functions. The tested flavonoids and [4″,5″] dihydro-obovatin increased nociceptive threshold and reduced the cell counting in the synovial lavage in the temporomandibular joint compared with the zymosan group. [4″,5”] dihydro-obovatin did not induce toxic effects as well as did not alter the motor function in the rota-rod test. The flavonoids and [4″,5″] dihydro-obovatin exerted antinociceptive and anti-inflammatory effects on the zymosan-induced temporomandibular joint inflammatory hypernociception in rats and the latter did not show significant toxic effects. Therefore, [4″,5″] dihydro-obovatin would be a promising anti-inflammatory and antinociceptive agent.