Bullatine A, a diterpenoid alkaloid of the genus Aconitum, could attenuate ATP-induced BV-2 microglia death/apoptosis via P2X receptor pathways.

Bullatine A (BLA), a diterpenoid alkaloid of the genus Aconitum, possesses anti-rheumatic, anti-inflammatory and anti-nociceptive effects. The mechanism underlying the effects was examined in the present study. The effect of BLA on extracellular ATP induced cell death/apoptosis and pro-inflammatory cytokines release were investigated using BV-2 microglia cell line. The mediation/efficacy of inflammatory cytokines and P2X receptors was evaluated by detecting the mRNA levels of iNOS, IL-6, IL-1ß and P2X receptors, respectively. The results demonstrated that BV-2 cells could be damaged after incubation with higher dose of ATP, leading to activation of pro-inflammatory cytokines, transcriptional activation of iNOS and overproduction of NO via activation of P2X receptor. The BLA (1-50µM) potently inhibits ATP-induced BV-2 cell death/apoptosis and P2X receptor-mediated inflammatory responses via selectively suppressing the up-regulation of P2X7 receptor mRNA. Since P2X7 receptors have an important role in immune and pain response, inflammation and inflammatory disease, this discovery of BLA as a potent P2X7 antagonist indicated that BLA may be a potential useful candidate for the treatment of neurodegenerative diseases such as arthritis.

Ethanolic extract of Aconiti Brachypodi Radix attenuates nociceptive pain probably via inhibition of voltage-dependent Na⁺ channel.

Aconiti Brachypodi Radix, belonging to the genus of Aconitum (Family Ranunculaceae), are used clinically as anti-rheumatic, anti-inflammatory and anti-nociceptive in traditional medicine of China. However, its mechanism and influence on nociceptive threshold are unknown and need further investigation. The analgesic effects of ethanolic extract of Aconiti Brachypodi Radix (EABR) were thus studied in vivo and in vitro. Three pain models in mice were used to assess the effect of EABR on nociceptive threshold. In vitro study was conducted to clarify the modulation of the extract on the tetrodotoxin-sensitive (TTX-S) sodium currents in rat's dorsal root ganglion (DRG) neurons using whole-cell patch clamp technique. The results showed that EABR (5-20 mg/kg, i.g.) could produce dose-dependent analgesic effect on hot-plate tests as well as writhing response induced by acetic acid. In addition, administration of 2.5-10 mg/kg EABR (i.g.) caused significant decrease in pain responses in the first and second phases of formalin test without altering the PGE2 production in the hind paw of the mice. Moreover, EABR (10 µg/ml -1 mg/ml) could suppress TTX-S voltage-gated sodium currents in a dose-dependent way, indicating the underlying electrophysiological mechanism of the analgesic effect of the folk plant medicine. Collectively, our results indicated that EABR has analgesic property in three pain models and useful influence on TTX-S sodium currents in DRG neurons, suggesting that the interference with pain messages caused by the modulation of EABR on TTX-S sodium currents in DRG neurones may explain some of its analgesic effect.