Bullatine A

Bullatine A, a diterpenoid alkaloid, is a potent P2X7 antagonist. Bullatine A possesses anti-rheumatic, anti-inflammatory and anti-nociceptive effects. Bullatine A inhibits ATP-induced BV-2 cell death/apoptosis and P2X receptor-mediated inflammatory responses. Bullatine A suppresses glioma cell growth by targeting SIRT6. Bullatine A specifically attenuates pain hypersensitivity in rats. Bullatine A attenuates LPS (HY-D1056)-induced systemic inflammatory response by inhibiting the ROS/JNK/NF-κB pathway in mice. Bullatine A improves despair behavior in Chronic chronic social defeat stress (CSDS) mice. Bullatine A can be used for the study of inflammation, glioblastoma (GBM) and depression^{[1][2][3][4][5]}. In Vitro:Bullatine A (1-50 μM, 24 h) inhibits ATP-induced BV-2 cell death, down-regulates mRNA levels of IL-6、IL-1β、iNOS, reduces overproduction of NO and IL-6, and selectively inhibits up-regulation of P2X7 receptor mRNA (without effect on P2X4 mRNA) in BV-2 cells^[1]. Bullatine A (1-100 μM, 6 h) dose-dependently stimulates prodynorphin expression in primary microglia with an EC₅₀ of 3.2 μM^[2].
Bullatine A (10-80 μM, 6 h) significantly inhibits LPS (HY-D1056)-induced mRNA expression of IL-1β, IL-6, iNOS and TNF-α in BV2 microglia and iBMDMs^[3].
Bullatine A (80 μM) inhibits LPS-induced IKKα/β、IκBα phosphorylation and NF-κB p65 nuclear translocation, decreases JNK phosphorylation but not p38、ERK1/2 phosphorylation in iBMDMs^[3].
Bullatine A (80 μM, 24 h) reduces LPS-induced intracellular ROS generation in iBMDMs^[3].
Bullatine A (50-800 nM, 7 days) dose-dependently reduces the colony-forming ability of U87MG and U251 cells^[4].
Bullatine A (5-45 μM, 24 h) dose-dependently increases the early and late apoptosis rates of U87MG cells, reduces mitochondrial membrane potential and induces G2/M phase cell cycle arrest in U87MG and U251 cells^[4].
Bullatine A (5-45 μM, 24 h) downregulates p-ERK and Myc and dose-dependently inhibits H3K9Ac、H3K56Ac while upregulating SIRT6 in U87MG cells^[4].
Bullatine A (50 μM, 24 h) inhibits eATP-induced mitochondrial calcium overload, increased ER-mitochondria colocalization, activation of PERK-elF-2α UPR, lysosome production, elevated NLRP3 inflammasome protein expression, and reduced viability in BV-2 cells^[5].
In Vivo:Bullatine A (0.3-30 mg/kg, s.c., cumulative doses at 1 h intervals ) dose-dependently attenuates mechanical allodynia and thermal hyperalgesia in spinal nerve ligation-induced neuropathic rats and Complete Freund’s adjuvant (CFA)-induced inflammatory pain rats^[2].
Bullatine A (0.3-30 mg/kg, s.c., cumulative doses at 1 h intervals ) mitigates mechanical allodynia in Walker 256-induced bone cancer pain rats and Streptozotocin (HY-13753)-induced neuropathic rats^[2].
Bullatine A (0.3-30 μg (10 μL), i.t., single dose) inhibits mechanical allodynia in neuropathic rats^[2].
Bullatine A (5-20 mg/kg, i.p., twice at 12 h and 1 h prior to LPS injection) attenuates LPS-induced systemic inflammatory response in mice^[3].
Bullatine A (10 μg/kg, i.g., once daily, 2 weeks) improves despair behavior in CSDS mice^[5].
Bullatine A (10 μg, intra-hippocampal microinjection, every two days, 10 days) partially ameliorates CSDS-induced depressive-like behaviors in hippocampal MAMs^[5].