TABLE 8

Phytochemicals that modify GSK-3β signaling

PhytochemicalTarget Tissue/CellsEffectsInvolved Molecular MechanismReference
EGCGHepG2 cellsInhibit lipogenesisMetabolic syndrome were mediated by GSK-3β inhibitionKim et al. (2013b)
Green tea polyphenolsCardiac muscle in insulin-resistant ratsReduce detrimental effects of a high-fructose diet on insulin signaling, lipid metabolism, and inflammationDecreased GSK-3βQin et al. (2010)
Citrus aurantium flavonoids3T3-L1 cellsInhibit adipogenesisMediated by the inhibition of GSK-3β phosphorylationKim et al. (2012)
Curcumin3T3-L1 cellsInhibit adipogenic differentiationReduced differentiation-stimulated expression of GSK-3βAhn et al. (2010)
Ellagic acidHamster buccal pouch carcinogenesis modelInduce apoptosisPreventing the constitutive activation of Wnt pathway through downregulation of GSK-3βAnitha et al. (2013)
Black tea polyphenolsPrEC and Du145 prostate carcinoma cellsInhibit IGF-I–mediated prostate cancer incidenceDecreased downstream effects of Akt activation including phosphorylation of GSK-3βKlein and Fischer (2002)
EGCGHuman skin cancer cell lineReduce cell viability and increased cell deathReduced phosphorylation of GSK-3βSingh and Katiyar (2013)
3,3′-DiindolylmethaneVSMC neointima formation in a carotid injury modelG0/G1 phase cell cycle arrest, inhibit infiltration of inflammatory cellActivities of downstream signaling molecules including GSK-3βGuan et al. (2012)
Oral squamous cell carcinoma Suppress the viability of the cells by inducing apoptosis and G2/M arrestInhibit downstream effectors of the GSK-3βWeng et al. (2012)
GenisteinPC3 cellsDecrease expression of β-cateninIncreased GSK-3Liss et al. (2010)
NimbolideHepG2 cellsAbrogate canonical NF-κB and Wnt signaling to induce caspase-dependent apoptosisApoptosis evasion by evaluating members of GSK-3βKavitha et al. (2012)
QuercetinBEAS-2B cellsDecrease the viability of the cells via apoptosisInactivated GSK-3βLee and Yoo (2013)
PuerarinPrimary hippocampal neuronsNeuroprotection against AβInhibited GSK-3β signalingZou et al. (2013)
(±)-CatechinMiceProtect dopaminergic neuronsModulate the rapid activation of GSK-3β against MPTP-induced dopaminergic neurotoxicityRuan et al. (2009)
Luteolin“Swedish” mutant APP transgene-bearing neuron-like cells and primary neuronsSignificantly reduce Aβ pathology and disrupt PS1-APP associationReduced GSK-3 activityRezai-Zadeh et al. (2009)
EGCGMutant hSOD1 gene (G93A) motoneuron cellsPrevent oxidative stress–induced deathInhibition of GSK-3βKoh et al. (2004)
bis-Indole indirubinSf9 cellsInhibit τ phosphorylation at AD-specific sitesPowerful GSK-3β inhibitorLeclerc et al. (2001)
MorinHippocampus of 3xTg-AD miceBlock GSK-3β–induced τ phosphorylation, and attenuate τ hyperphosphorylation in 3xTG-AD miceInhibited GSK-3β activityGong et al. (2011)
  • 3xTg-AD, triple transgenic AD; PS1, presenilin 1; VSMC, vascular smooth muscle cell.