Table 5 Antioxidants influence PI3K/Akt and/or activities

 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.

[163–166]

 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.

[171–173]

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.

[174–176]

 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.

[180–183]

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.

[195–198]