title: Bullatine A, a diterpenoid alkaloid of the genus Aconitum, could attenuate ATP-induced BV-2 microglia death/apoptosis via P2X receptor pathways.
abstract: 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-1β 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.
authors.affiliation: College of Pharmacy, South-Central University for Nationalities, Wuhan 430074, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.forename: Xian-Ju
authors.initials: XJ
authors.lastname: Huang
authors.forename: Da-Jiang
authors.initials: DJ
authors.lastname: Zou
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
mesh_terms: D031841:Aconitum / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D058848:Receptors, Purinergic P2X4 / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism
chemical_list: D000470:Alkaloids; D016207:Cytokines; D004224:Diterpenes; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; C587049:bullatine A; D000255:Adenosine Triphosphate
keywords: Anti-inflammation; BV-2; Bullatine A; P2X receptor; Pain