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Table 5 Antioxidants influence PI3K/Akt and/or activities

From: Chronic over-nutrition and dysregulation of GSK3 in diseases

Antioxidants Model system Observed effects Ref.
 Anthocyanidins Hypercholesterolaemic patients, human stomach cancer cells, human breast cancer cells, human hepato-carcinoma cells. Suppress PI3K/Akt signaling pathway via epidermal growth factor receptor pathway, or levels of pSGSK3β and β-catenin in a tumor xenograft model. [163166]
 Mulberry anthocyanidin Human liver cancer cells. Activate PI3K/Akt. [167]
 Berberine Human melanoma cells, SD rats. Inhibit PI3K/Akt and/or GSK3β activities. [52, 168]
Murine neural crest cells, murine primary neurons, mice with cerebral and reperfusion, human chondrosarcoma cells. Increase PI3K/Akt activities and cell growth/survival in other studies. [169, 170]
 Curcumin Human Burkitts’ lymphoma, human esophageal cancer cells, human renal cancer cells. Enhance radiation- or PI3K/Akt inhibitors-induced or directly induce apoptosis by suppression of PI3K/Akt signaling pathway. [171173]
Rat cardiomyocytes, human prostate cancer cells, Balb/c mice. Protect cells from apoptosis induced by a high glucose level via upregulation of Akt/GSK3β serine/threonine phosphorylation levels via protein phosphatase-dependent mechanism or inhibits GSK3β activity in vitro or in vivo. [174176]
 Ergosterol Streptozotocin-induced diabetes in mice, human cancer cells. Restore PI3K/Akt signaling damaged in diabetic mice; ergosterol-related compounds induce cell apoptosis depending on a protein-promoted Akt activation. [177, 178]
 Garlicin Human cellosaurus cells Suppress PI3K/Akt pathway. [179]
 Garlic Fructose-fed diabetic SD rats Activate PI3K/Akt in Diabetes rats. [96]
 Luteolin Human epidermoid carcinoma cells and their murine cells xenograft model, human umbilical vein endothelial cells, human prostate cancer cells, human colon cancer cells, human glioblastoma cells. Inhibit VEGF-increased PI3K/Akt activities or IGF-1-increased the phosphorylation levels of PI3K/Akt/GSK3 or down-regulate PI3K/Akt pathway. [180183]
Cardiomyocyte in rats with ischemia/reperfusion, murine neural crest cells. Decrease apoptosis via PI3K/Akt pathway in a rat model or persistently activate Akt in cells. [184, 185]
 Lycopene Prostate epithelial cells. Inhibit IGF-1-induced Akt/GSK3 serine/threonine phosphorylation levels. [83]
Patients, human prostate cells. Its effects on PI3K/Akt pathway are inhibitory in prostate cancer. [186]
 Phytoestrogens Human embryonic kidney cells, mouse preosteoblastic cells. Increase phosphorylation levels of Akt and GSK3β as well as the Wnt/β-catenin signaling. [187]
 Isoflavones Human cancer cells Inhibit PI3K/Akt signaling in cancer cells. [188]
 Soy isoflavone SD rats with myocardial ischemia/reperfusion. Gain PI3K/Akt pathway activities in ovariectomized rats. [189]
 Daidzein or genistein Nude mice with various tumors Up-regulate or down-regulate GSK3 gene/protein expression, and both belong to isoflavones. [190]
 Psoralidin Human lung fibroblasts, mice. A coumestan derivative suppresses pro-inflammatory cytokines and regulates PI3K/Akt pathway. [191]
 Resveratrol Mouse cardiac fibroblasts, human glioma cells. Inhibit high glucose-induced PI3K/Akt pathway and inflammation or reduces PI3K/Akt activities. [63, 192]
Neural crest cells, APP/PS1 mice. Protect cells from apoptosis induced by high glucose via activation of PI3K/Akt pathways and increase in vivo pSGSK3β levels. [193, 194]
 Lignan including  honokiol and  sauchinone Human prostate cancer cells, human myeloid leukaemic cells, mouse microphage, mouse lymphoblast, splenic lymphocytes, human glioma, breast and prostate cancer cells, human hepatocytes, WT and a Nrf2 KO C57/BL6 mice. Inhibits Akt signaling and generate anti-inflammatory effect via inhibition of PI3K/Akt pathway or mediate suppression of PI3K; however sauchinone, augments in vivo pSGSK3β levels. [195198]
  1. a Nrf2 nuclear factor (erythroid derived 2)-like 2