Polygalasaponin F

Polygalasaponin F is an orally active triterpenoid saponin monomer. Polygalasaponin F downregulates the expression of Bax, p53, caspase-3, NF-κB p65 and MEK1; restores and upregulates the expression of Bcl-2; activates the PI3K/Akt signaling pathway; inhibits the phosphorylation of p38 MAPK, nuclear translocation of NF-κB, TLR4-mediated signaling pathway, mitophagy (Mitophagy) and ROS production; enhances cell viability and suppresses apoptosis (Apoptosis). Polygalasaponin F maintains mitochondrial function, alleviates Ca²⁺ overload, upregulates pCREB and BDNF, preserves cell viability and inhibits the release of inflammatory cytokines. Polygalasaponin F alleviates lung injury induced by influenza A H1N1 and cerebral ischemia-reperfusion injury. Polygalasaponin F is applicable to researches related to Parkinson's disease, cerebral ischemia, pneumonia induced by influenza A H1N1, stroke and Alzheimer's disease^{[1][2][3][4][5][6][7]}. IC50 & Target:TLR4-PI3K/AKT-NF-kB^[1] In Vitro:Polygalasaponin F (0.1-10.0 μM; 24-48 h) increases the survival rate of PC12 cells damaged by Rotenone (HY-B1756), reduces cell apoptosis, inhibits intracellular ROS production, preserves mitochondrial membrane potential, reverses cellular ATP depletion, suppresses the release of cytochrome c from mitochondria to the cytoplasm, regulates the expression of apoptotic proteins, decreases p53 levels, restores the normal Bax/Bcl-2 ratio, and inhibits the activation of caspase-3^[1].
Polygalasaponin F (0.1-10 μM) significantly increases the viability of PC12 cells and primary rat cortical neurons treated with oxygen-glucose deprivation/reoxygenation (OGD/R), and upregulates the Bcl-2/Bax ratio in the cells^[2].
Polygalasaponin F (0.1-10 μM) downregulates the expression of activated caspase-3 in primary rat cortical neurons treated with OGD/R, suggesting a reduction in the level of cellular apoptosis^[2].
Polygalasaponin F (1-10 μM) activates the PI3K/Akt signaling pathway in OGD/R-treated PC12 cells^[2].
Polygalasaponin F (0.1-10 μM; 1 h pre-treatment followed by 24 h incubation with LPS) dose-dependently inhibits LPS (HY-D1056)-induced TNF-α secretion in BV-2 microglia, suppresses the production of NO and iNOS protein in cells, inhibits p38 MAPK phosphorylation, and increases cell viability^[3].
Polygalasaponin F (0.1-10 μM; 1 h pretreatment, 24 h LPS co-incubation) inhibits LPS-induced NF-κB activation in BV-2 microglia in a dose-dependent manner by reducing p65 nuclear translocation and increasing cytoplasmic p65 and IkB-α levels^[3].
Polygalasaponin F (10^-5 M; 24 h) inhibits LPS-induced nuclear translocation of the NF-κB p65 subunit in BV-2 microglia and reduces the phosphorylation level of AKT in cells via a PI3K/AKT-dependent mechanism^[4].
Polygalasaponin F exerts anti-inflammatory effects in LPS-stimulated RAW264.7 macrophages and BV2 microglia by inhibiting the production of nitric oxide and prostaglandin E₂, reducing the mRNA expression levels of pro-inflammatory cytokines, and suppressing the activation of the NF-κB pathway^[5].
Polygalasaponin F (2-10 μM; 30 min pre-incubation followed by 24 h co-treatment with 100 μM glutamate) concentration-dependently increases the survival rate of primary cultured rat embryonic hippocampal neurons subjected to glutamate-induced cytotoxicity^[6].
Polygalasaponin F (10 μM; 24 h co-treatment with 100 μM glutamate) inhibits glutamate-induced apoptosis of primary cultured rat embryonic hippocampal neurons and increases the count of caspase-3-positive cells^[6].
Polygalasaponin F (10 μM; 4 h co-treatment with 100 μM glutamate) inhibits glutamate-induced intracellular Ca²⁺ overload in primary cultured rat embryonic hippocampal neurons by blocking extracellular Ca²⁺ influx^[6].
Polygalasaponin F (10 μM) partially blocks NMDAR-mediated currents in primary cultured rat embryonic hippocampal neurons, inhibiting the current amplitude by 47.7%. It reverses the dysregulated expression of NMDAR subunits induced by glutamate in neurons, restores the levels of NR2A and NR2B to near those of the control group, and reverses the downregulated expression of pCREB and BDNF^[6].
Polygalasaponin F (40 μM; 6 h) protects HT22 mouse hippocampal neurons against OGD/R injury by alleviating oxidative stress, preserving mitochondrial function, inhibiting excessive mitophagy, and attenuating apoptosis^[7]. In Vivo:Polygalasaponin F (p.o., once daily for 5-7 days at 50-200 mg/kg) protects mice against pneumonia injury induced by influenza A (H1N1) virus by alleviating body weight loss, improving survival rate, reducing pulmonary inflammatory responses and viral load, inhibiting the production of proinflammatory cytokines and prostaglandins, and suppressing the expression of NF-κB and Raf/MEK/ERK pathway proteins^[5].
Polygalasaponin F (i.p., once daily for 10 days, 15-30 mg/kg) dose-dependently alleviates cerebral ischemia-reperfusion injury in male KM mice; at the dose of 30 mg/kg, it reduces cerebral infarct volume by approximately 55% compared with the model group, while inhibiting neuronal apoptosis and blocking excessive mitophagy^[7].