Pongamol

Pongamol is an orally active flavonoid with an IC₅₀ of 75 μM and a K_i of 58 μM against PTPase-1B, and an IC₅₀ of 103.5 μM against intestinal α-Glycosidase. Pongamol reduces the release of IL‑1β, TNF‑α, COX‑2 and iNOS in cells, reverses the nuclear translocation of NF‑κB, and upregulates the levels of Beclin 1 and LC3 Ⅱ/LC3 Ⅰ. Pongamol promotes glucose uptake by increasing the level of GLUT4 on the surface of skeletal muscle cells. Pongamol inhibits epithelial-mesenchymal transition by suppressing the FAK/Akt-mTOR signaling pathway. Pongamol inhibits neuronal cytotoxicity, suppresses cell apoptosis and extends the lifespan of Caenorhabditis elegans by activating the MAPKs/Nrf2 signaling pathway. Pongamol exerts hypoglycemic effects in diabetic mouse models. Pongamol alleviates oxidative stress, neuroinflammation, Aβ deposition and excessive phosphorylation of Tau Protein, and restores autophagy function in Alzheimer's disease mouse models by inhibiting the Akt/mTOR signaling pathway. Pongamol is applicable to research related to Alzheimer's disease, type 2 diabetes, non-small cell lung cancer and postprandial hyperglycemia^{[1][2][3][4][5][6]}. In Vitro:Pongamol (25-100 μM, pre-incubated for 1 h followed by LPS stimulation for 24 h) inhibits LPS (HY-D1056)-induced NO release in BV2 mouse microglia. It suppresses LPS-induced activation of the NF-κB pathway in cells by reducing IκB phosphorylation and blocking NF-κB nuclear translocation, and downregulates the expression of pro-inflammatory genes (IL-1β, TNF-α, iNOS, COX-2) in cells^[1].
Pongamol (100 μM, pretreated for 1 h followed by LPS stimulation for 24 h) reduces the levels of proinflammatory proteins (IL-6, IL-1β) and upregulates the expression of autophagy markers (Beclin 1, LC3 II/LC3 I) in LPS-stimulated mouse BV2 microglial cells, and these effects depend on the Akt pathway^[1].
Pongamol (0-10 μM; 0-16 h) increases both basal and insulin-superimposed glucose uptake in L6-GLUT4myc myotubes, elevates both basal and insulin-enhanced GLUT4 translocation to the cell surface by activating PI3-kinase activity, and potentiates Insulin (HY-P0035)-induced AKT (Ser-473) phosphorylation in myotubes^[2].
Pongamol (0-100 μM, 2 h) increases the survival rate of H₂O₂-induced PC12 cells, reduces LDH release, inhibits cell apoptosis, restores mitochondrial membrane potential, decreases the levels of pro-apoptotic proteins and increases the levels of anti-apoptotic proteins, suppresses the activation of the MAPKs signaling pathway (reduces the levels of p-ERK, p-JNK and p-p38), elevates GSH levels and reduces ROS levels, promotes Nrf2 nuclear translocation, upregulates the expression of downstream antioxidant genes and directly binds to Keap1, thereby activating the Nrf2/HO-1 signaling pathway^[3].
Pongamol (0-100 μM; 24-48 h) reduces the viability of H460 non-small cell lung cancer cells in a dose-dependent manner, and inhibits cell proliferation, anchorage-independent growth, migration and invasion^[4].
Pongamol (25-100 μM; 24 h) upregulates the epithelial marker E-cadherin, downregulates the mesenchymal markers N-cadherin, vimentin, Slug and Snail, inhibits the activation of the FAK/Akt-mTOR signaling pathway, and reduces the levels of phosphorylated FAK, Akt and mTOR in H460 non-small cell lung cancer cells^[4].
Pongamol (Compound 1) potently inhibits recombinant protein tyrosine phosphatase-1B (PTPase-1B) in cell-free assays, with an IC₅₀ of 75 μM and a K_i of 58 μM^[5].
Pongamol (Compound 6) potently inhibits rat intestinal α-glucosidase with an IC₅₀ of 103.5 μM^[6]. In Vivo:Pongamol (10-20 mg/kg; i.g.; daily; 4 weeks) improves spatial learning and memory abilities in mice with Alzheimer's disease induced by D-gal/NaNO₂/AlCl₃ via inhibiting the Akt/mTOR signaling pathway, alleviates oxidative stress, neuroinflammation, Aβ deposition and excessive phosphorylation of Tau protein, and restores autophagic function^[1].
Pongamol (15-60 μM; in NGM medium; administered from the L1 stage to the adult/L4 stage for 1-5 days) increases the head thrashing activity of the BR5270 Caenorhabditis elegans Alzheimer's disease model expressing human Tau protein, suggesting improved neuronal function. It enhances autophagic activity in the DA2123 Caenorhabditis elegans autophagy reporter model, and reduces lipofuscin deposition levels and Aβ mRNA expression in Caenorhabditis elegans Alzheimer's disease models expressing human Aβ/Tau^[1].
Pongamol (50-100 mg/kg; i.g.; single administration) exerts significant dose-dependent hypoglycemic effects in streptozotocin (HY-13753)-induced diabetic rats^[5].
Pongamol (100 mg/kg; i.g.; daily; for 10 consecutive days) exerts a significant and sustained hypoglycemic effect in type 2 diabetic db/db mice^[5].