Tabersonine

Tabersonine is a selective, orally active NLRP3 inhibitor. Tabersonine directly binds to the NACHT domain of NLRP3, inhibiting its ATPase activity and oligomerization, thereby blocking ASC spot formation and caspase-1 activation, and reducing the release of pro-inflammatory cytokines such as IL-1β. Tabersonine also inhibits K63-linked ubiquitination of TRAF6, blocking NF-κB, PI3K/Akt, and p38 MAPK signaling pathways. Tabersonine can inhibit inflammatory responses, induce apoptosis of liver cancer cells through mitochondrial pathways and death receptor pathways, reduce mitochondrial membrane potential, promote cytochrome c release, and activate caspase proteins. Tabersonine is mainly used in the study of NLRP3-driven inflammatory diseases (such as acute lung injury, sepsis, peritonitis) and tumors such as liver cancer^[1][2][3]. In Vitro:Tabersonine (0.78-25 μM; 24 h) inhibits the cell viability of human liver cancer cells SMMC-7721, HepG2 and human normal liver cells HL-7702, with a stronger inhibitory effect on liver cancer cells^[1].
Tabersonine (6.25-25 μM; 24 h) induces apoptosis of human liver cancer cells SMMC-7721, upregulates the expression of Bax, cleaved-caspase-3, and cleaved-PARP proteins, and downregulates the expression of Bcl-2 protein^[1].
Tabersonine (12.5-25 μM; 24 h) arrests the cell cycle of SMMC-7721 cells at the G0/G1 phase, and downregulates the expression of CDK4 and Cyclin D1 proteins^[1].
Tabersonine (25 μM; 6 h, 12 h, 24 h) inhibits the mRNA and protein expressions of NLRP3, ASC, cleaved-caspase-1, and IL-1β in SMMC-7721 cells^[1].
Tabersonine (6-30 μM; 18 h) induces apoptosis in HepG2 cells, resulting in mitochondrial function impairment, and PI3K/Akt pathway inhibition^[2].
Tabersonine inhibits NLRP3-mediated IL-1β production in BMDM cells with an IC₅₀ of 0.71 μM^[3]. In Vivo:Tabersonine (10-40 mg/kg; intraperitoneal injection; once a day; 30 days) reduces lung tissue pathological damage, inhibits neutrophil infiltration, reduces MPO activity and TNF-α, IL-6, and IL-1β levels in the mouse LPS-induced acute lung injury model^[1].
Tabersonine (25, 50 mg/kg; oral gavage; once a day; 3 weeks) significantly inhibits tumor growth in the nude mouse HepG2 liver cancer xenograft model, induces the expression of cleaved Caspase-3 in tumor tissues and promotes cell apoptosis^[2].
Tabersonine (10 mg/kg; gavage; 3 times a day; 48-120 h) inhibits NLRP3 inflammasome activation, reduces IL-1β release and inflammatory cell infiltration in the mouse LPS-induced acute lung injury and Alum-induced peritonitis models; and increases the 48-hour survival rate of mice to 60% in the Escherichia coli-induced sepsis model^[3].