Crebanine

Crebanine is an isoquinoline-like alkaloid that can be derived from Stephania. Crebanine is an antagonist of the α7-nAChR with an IC₅₀ of 19.1 μM. Crebanine suppresses the proliferation, migration, and invasion of cancer cells, triggers reactive oxygen species (ROS) burst, and promotes apoptosis. Crebanine inhibits the AKT/FoxO3a, NF-κB and MAPK signaling pathways. Crebanine attenuates NOX2 hyperactivation, exhibits antioxidant properties by reducing reactive oxygen species and peroxidation in microglia cells. Crebanine inhibits voltage-dependent Na⁺ current in guinea-pig ventricular myocytes. Crebanine has high inhibitory activity against gram-positive animal pathogenic bacteria. Crebanine ameliorates ischemia-reperfusion brain damage in middle cerebral artery occlusion and reperfusion (MCAO/R) rats. Crebanine significantly improves Scopolamine (HY-N0296)-induced cognitive deficits in ICR mice. Crebanine can be used for the study of hepatocellular carcinoma (HCC), cerebral ischemia and Alzheimer's disease^{[1][2][3][4][5][6]}. In Vitro:Crebanine (0-280 μM, 24-72 h) suppresses cell growth, reduces colony formation ability and inhibits migration and invasion of HepG2 cells^[1].
Crebanine (35-175 μM, 24 h) reduces mitochondrial membrane potential (MMP) and induces apoptosis rate in HepG2 cells^[1].
Crebanine (35-175 μM, 24 h) increases intracellular ROS levels, enhances MDA production, and decreases SOD and GSH-PX activities in HepG2 cells, an effect that can be reversed by Acetylcysteine (NAC) (HY-B0215) pretreatment^[1].
Crebanine (35-175 μM, 24 h) down-regulates p-AKT and p-FoxO3a (Ser253) in HepG2 cells in a dose-dependent manner without affecting total AKT and FoxO3a levels^[1].
Crebanine (1-20 μM, pretreated for 2 h, then co-treated with LPS for 24 h) inhibits NOX2 activation in BV-2 cells by reducing NADP⁺/NADPH levels, downregulating gp91^phox and p47^phox expression, and decreasing p47phox membrane translocation^[2].
Crebanine (1-20 μM, pretreated for 2 h, then co-treated with LPS (HY-D1056) for 24 h) reduces intracellular superoxide anion, ROS, and MDA levels, suppresses NO, iNOS, IL-1β, IL-6, and TNF-α expression, and inhibits NF-κB and MAPK signaling pathways^[2].
Crebanine (0-30 µg/mL, 48 h) inhibits proliferation of HL-60, U937, K562, HT1080, KB-3-1 and KB-V1 cells in a concentration-dependent manner with IC₅₀ values of 9, 12, 13, 20, 24 and 16 µg/mL respectively, and shows slight toxicity to normal fibroblast cells (72% survival at 30 µg/mL)^[3].
Crebanine (0-30 µg/mL, 24 h) induces G0/G1 phase arrest and induces apoptosis in HL-60 and U937 cells^[3].
Crebanine (20 µg/mL, 0-24 h) down-regulates the expression of cyclins A, D1, PCNA, Bcl-2 and Bcl-xl and enhances Bax expression in HL-60 cells, while cyclin E expression remains unchanged^[3].
Crebanine (0.0368-0.7366 mM) reversibly inhibits voltage-dependent Na⁺ current in guinea-pig ventricular myocytes in a concentration-dependent manner, with an IC₅₀ of 0.283 mM; the effect partially recovers after 5 min washout^[4].
Crebanine (10 μM) significantly inhibits the binding of (±)-[³H]-epibatidine to Ls-AChBP, Ac-AChBP and AcY55W-AChBP, with K_i values of 179 nM, 538 nM and >1000 nM respectively^[5].
Crebanine (10.3 μM) exhibits antagonistic effects on α7-nAChR, α4β2-nAChR, (α1)2β1δγ-nAChR and 5-HT3A receptor in mammalian cells, with inhibition percentages of 100.7%, 29.0%, 81.7% and 55.3% respectively^[5].
Crebanine exhibits high inhibitory activity against gram-positive animal pathogenic bacteria, with an MIC of 0.312 g/L against Micrococcus lysodeikticus, Bacillus megaterium, Bacillus subtilis and Staphylococcus aureus, and an MIC of 0.213 g/L against Bacillus cereus^[6].
Crebanine inhibits hyphal growth of these 5 plant pathogenic fungi (EC₅₀: 0.111 g/L for Cercospora kaki; 6.47×10^-2 g/L for Gymnosporangium haraeanum; 1.89×10^-2 g/L for Pyricularia oryzae; 4.25×10^-2 g/L for Rhizoctonia solani; 4.05×10^-2 g/L for Colletotrichum graminicola)^[6].
Crebanine (0.4 g/L) inhibits spore germination of Thielaviopsis paradoxa (94.96%), Fusarium oxysporum f. sp. niveum (100%), Sphaceloma fawcettii (100%) and Gymnosporangium haraeanum (100%)^[6].
In Vivo:Crebanine (250-500 μg/kg, after 2 h MCAO occlusion followed by 24 h reperfusion) ameliorates neurological deficits, reduces brain water content and infarct volume in MCAO/R rats^[2].
Crebanine (8.5 mg/kg (25 μmol/kg), i.p., single dose) significantly improves Scopolamine (HY-N0296)-induced cognitive deficits in ICR mice^[5].