|
| Compound | Experimental model | Key findings | Reference |
|
| Pinocembrin | Human neuroblastoma SH-SY5Y cells exposed to hydrogen peroxide (H2O2) (4 h pretreatment (25 μM)) | Protects cells from H2O2-induced cell death and mitochondrial depolarization; ameliorates redox impairment in mitochondrial membranes; suppresses O2- and NO production; recovers the suppressed tricarboxylic acid (TCA) cycle enzymes aconitase, alpha-ketoglutarate dehydrogenase, and succinate dehydrogenase; inhibits the activation of NF-κB and levels of IL-1β and TNF-α; all effects were dependent on the HO-1 enzyme and on the activation of Nrf2—confirmed by HO-1 inhibition (with 0.5 μM ZnPP IX) or Nrf2 silencing (with small interfering RNA (siRNA)). | de Oliveira et al. [35] |
|
| Pinocembrin | SH-SY5Y cells exposed to methylglyoxal (pretreatment with 0-25 μM for 4 h) | Ameliorates mitochondrial dysfunction—decreases lipid peroxidation, protein carbonylation, and protein nitration in mitochondrial membranes; suppresses mitochondrial free radical production; increases glutathione (GSH) level in mitochondria; rescues mitochondrial membrane potential (MMP); inhibits cell death through activation of the extracellular-related kinase (Erk1/2) and consequent upregulation of Nrf2; increases the levels of GPx, GR, HO-1, and mitochondrial GSH; all effects could be abolished by silencing of Nrf2 with siRNA. | de Oliveira et al. [36] |
|
| Pinocembrin | SH-SY5Y neuroblastoma cells exposed to paraquat (pretreatment for 4 h) | Suppresses the levels of Bcl-2-associated X protein (Bax); inhibits cytochrome c release to the cytosol and caspase-9 and caspase-3 activation; inhibits mitochondrial dysfunction by ameliorating the inhibition of complexes I and V; inhibits the loss of MMP and the decline in ATP levels; antioxidant effects on mitochondria coupled with decreased levels of redox impairment markers; enhances the levels of mitochondrial GSH; effect dependent on activation of the Erk1/2-Nrf2 axis—inhibition of Erk1/2 or silencing of Nrf2 abrogated these effects. | de Oliveira et al. [37] |
|
| Pinocembrin | SH-SY5Y cells exposed to neurotoxin 6-hydroxydopamine- (6-OHDA-) induced cell death in pretreatment for 4 h | Improves cell viability and apoptotic rate and decreases Bcl-2/Bax ratio; inhibits oxidative stress (ROS, the level of malondialdehyde, MMP, and SOD); increases Nrf2 protein levels and subsequent activation of ARE pathway genes of HO-1 and gamma-glutamylcysteine synthetase (γ-GCS); treatment with Nrf2 small interfering RNA abolished protective effects. | Jin et al. [38] |
|
| Pinocembrin | SH-SY5Y exposed to neurotoxic 1-methyl-4-phenylpyridinium (MPP+) | Inhibits the induced cell death by increasing HO-1 expression—inhibitor of HO-1 zinc protoporphyrin IX abolished the neuroprotective effect; induces phosphorylation of ERK1/2—cytoprotective effect can be abolished by ERK1/2 inhibitors. | Wang et al. [39] |
|
| Pinocembrin | SH-SY5Y cells exposed to Aβ25-35 (4 h pretreatment) | Inhibits mitochondrial dysfunctions (lowered MMP, decreased Bcl-2/Bax ratio); inhibits cytochrome c release and caspase-3 cleavage; increases protein levels of Nrf2 and induces HO-1 expression; neuroprotective effects abolished by RNA interference-mediated knockdown of Nrf2 expression or HO-1 inhibitor zinc protoporphyrin IX (ZnPP). | Wang et al. [40] |
|
| Pinocembrin | LPS-stimulated BV-2 microglial cells | Inhibits TNF-α, IL-1β, NO, and PGE2 production; suppresses iNOS and COX-2 expression; inhibits phosphoinositide 3-kinase (PI3K), Akt phosphorylation, and NF-κB activation; induces nuclear translocation of Nrf2 and expression of HO-1. | Zhou et al. [41] |
|
