Ponicidin

Ponicidin is an apoptosis inducer, cell growth inhibitor and neuroprotective agent, with a K_a of 135 nM for mouse RIPK1. Ponicidin regulates the JAK2/STAT3 pathway to induce apoptosis, activates the PI3K/Akt pathway, upregulates SIRT1 expression, alleviates oxidative stress, inhibits inflammatory responses and necroptosis, and blocks cell cycle progression. Ponicidin induces ROS production to exert antiproliferative and antiviral effects, while also improving cognitive function and reducing Aβ plaque deposition. Ponicidin is applicable to research related to hepatocellular carcinoma, Alzheimer's disease and gastric cancer^[1][2][3][4]. IC50 & Target:Apoptosis^[1] In Vitro:Ponicidin (5-40 μmol/L; 24-72 h) inhibits the viability of QGY-7701 and HepG-2 human hepatocellular carcinoma cells in a dose- and time-dependent manner, with 40 μmol/L for 72 h reducing viability to 9.3% (QGY-7701) and 12.7% (HepG-2)^[1].
Ponicidin (40 μmol/L; 48 or 72 h) down-regulates Survivin and Bcl-2 (mRNA and protein) and up-regulates Bax (mRNA and protein) in QGY-7701 and HepG-2 human hepatocellular carcinoma cells^[1].
Ponicidin (1-50 μM; 24 h) shows no significant cytotoxicity to HT-22 mouse hippocampal neuronal cells, and ponicidin (10 μM; 2 h pre-incubation) significantly restores cell viability reduced by Aβ_1-42 exposure^[2].
Ponicidin (10 μM; 2 h pre-incubation) significantly mitigates Aβ_1-42-induced neuroinflammation in HT-22 mouse hippocampal neuronal cells by downregulating pro-inflammatory cytokines (TNF-α, IL-1β) and upregulating anti-inflammatory IL-10^[2].
Ponicidin (10 μM; 2 h pre-incubation) significantly reduces Aβ_1-42-induced intracellular ROS generation and oxidative stress in HT-22 mouse hippocampal neuronal cells by lowering lipid peroxidation and restoring antioxidant enzyme activity^[2].
Ponicidin (10 μM; 2 h pre-incubation) significantly upregulates SIRT1 expression and modulates PI3K/Akt pathway activation in Aβ_1-42-treated HT-22 mouse hippocampal neuronal cells, with effects reversed by SIRT1 inhibition^[2].
Ponicidin (10 μM; 2 h pre-incubation) significantly enhances BDNF and NGF expression in Aβ_1-42-treated HT-22 mouse hippocampal neuronal cells via a SIRT1-mediated mechanism^[2].
Ponicidin (10-50 μmol/L; 48 h) induces dose-dependent apoptosis of human gastric carcinoma MKN28 cells, with early apoptotic cell levels reaching 59.03%% at 50 μmol/L^[3].
Ponicidin (10-50 μmol/L; 48 h) induces a dose-dependent G0-G1 cell cycle arrest in human gastric carcinoma MKN28 cells, increasing G0-G1 phase cells to 60.68% ± 0.78% at 50 μmol/L while reducing S and G2-M phase cell populations^[3].
Ponicidin (10-50 μmol/L; 1-48 h) induces time- and dose-dependent activation of caspase-3 in human gastric carcinoma MKN28 cells, with activity reaching 28.76% ± 0.38% at 50 μmol/L for 48 h^[3].
Ponicidin (0.781-25 nM; association and dissociation phases monitored over time) binds directly and stably to recombinant mouse RIPK1 protein with a K_d of 135 nM^[4].
Ponicidin (1.56-100 μM; 8 h) has a CC₅₀ of 59.360 ± 3.58 μM in BV2 microglial cells, showing low cytotoxicity at 5 μM^[4].
Ponicidin (5 μM; 30 min (pre-incubation); 8 h (LZ stimulation)) inhibits LZ-induced secretion of TNF-α (IC₅₀ 3.56 ± 0.421 μM) and IL-6 (IC₅₀ 2.635 ± 0.306 μM) in BV2 microglial cells, with significant suppression observed at 5 μM^[4].
Ponicidin (5 μM; 30 min (pre-incubation); 8 h (TZ stimulation)) inhibits TZ-induced LDH release, protecting HT22 neuronal cells from membrane damage associated with necroptosis^[4].
Ponicidin (5 μM; 30 min (pre-incubation); 4 h (TZ stimulation)) inhibits neuronal necroptosis by blocking the RIPK1-RIPK3-MLKL signaling cascade, reducing phosphorylation of RIPK1, RIPK3, and MLKL in TZ-stimulated HT22 neuronal cells^[4]. In Vivo:Ponicidin (5-10 mg/kg/day; oral; daily; 30 days) significantly improves cognitive function, reduces Aβ plaque deposition, and inhibits neuroinflammation and necroptosis in 5×FAD transgenic mice^[4].