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Table 6 Condiments or ingredients in drinks modulate PI3K/Akt and/or GSK3 activities

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

Nutrient Model system Observed effects Ref.
Condiments    
 Capsaicin aTRPV1-KO and wild-type C57BL/6 mice. Exert its effect through the capsaicin receptor that is the transient receptor potential cation channel subfamily V member 1 (TRPV1). [199]
Human prostate cancer cells. Regulate PI3K/Akt pathway in cultured cells and can activate microglia in mouse spine cord at a very low concentration. [200]
Rat spinal cord ERK activation is detected in microglia of animal spine cord by capsaicin stimulation. [201]
SD rats, astrocytes and microglia from the rats, human microglia cells. Capsaicin-activated TRPV1 mediates microglia death via calcium signaling. [202]
Human colorectal cancer cells. Increase association of c/EBPβ and GSK3β, which is suggested to mediate capsaicin-induced apoptosis. [203]
 Monosodium glutamate (MSG) Rodent striatal cholinergic interneurons. Contain glutamate which is a non-essential amino acid and its receptor is glutamate receptor, belonging to GPCR. [204]
  Animal nervous systems Neurotransmitters in the brain; whether MSG clinically associates with neurologic diseases remains to be studied. [205]
SD rats, mouse hippocampal neuronal cells, hippocampal neurons and brain cortex from SD rats. Induce neurodegeneration is suggested via PI3K/Akt pathway regulation and injection of glutamate into animals generates neurotoxicity via GSK3β. [147, 148, 206]
 Ingredients in drinks Animal nervous systems. A central nervous system (CNS) stimulant and cause biological effects via adenosine receptors that belong to GPCR. [207209]
 Caffeine Human neuroblastoma cells, HeLa cells, mouse neural crest cells, mouse adipocytes. Activate PI3K/Akt pathway and prevent cell death; or induce cell apoptosis by suppressing PI3K/Akt signaling and decrease phosphorylation levels of Akt/GSK3β. [210212]
Patients. Excess caffeine can lead to caffeine intoxication (i.e. overstimulation of CNS). [213]
 Ethanol Ethanol-induced fatty liver in mice, aAA and ANA rats. Presented in liquor can acutely induce hepatosteatosis, a process associated with PI3K/Akt activation and phosphorylation levels of Akt and GSK3β in the rat cortex. [214, 215]
Human vascular endothelial cells. Low concentrations of ethanol activate PI3K/Akt signaling, inhibiting GSK3 activity, whereas high concentrations of ethanol induce caspase-3 activation and increases apoptosis [216]
Human cells, C57BL/6 mice. Ethanol is metabolized to acetaldehyde by alcohol dehydrogenase in the body, and acetaldehyde is further metabolized by aldehyde dehydrogenases (ALDH). [217, 218]
Human hepatic stellate cells. The acetaldehyde-enhanced gene expression requires PI3K activation. [219221]
C57BL/6 mice Ethanol administration reduces phosphorylation levels of Akt and GSK3β, which is aggravated in cardiomyocyte without ALDH-2. [218]
 Tea Components analyzed. Have ingredients including caffein, polyphenols and catechin containing abundant epigallocatechin gallate (EGCG). [222]
 Tea polyphenols Mouse skin epithelial cells, human normal and keloid fibroblasts, the cultured human keloid model. Humans. Have inhibitory effects on PI3K pathway and suppress PI3K/Akt proteins expression and/or Akt activity in vitro and in vivo in prostate cancer models, may play roles in prevention of prostate cancer. [223225]
 EGCG Human hepatocyte derived cellular carcinoma cells, human pancreatic carcinoma cells. Block cell growth and induces cell apoptosis via inhibition of VEGF signaling pathway including Akt or downregulation of Akt activity. [226, 227]
Human alveolar basal epithelial cells, human neuroblastoma cells expressing bAPP-C99. Raise cell viability by its induction of Akt activity and suppression of GSK3β activity and inhibit β-amyloid-induced neurotoxicity by suppression of GSK3β activation. [228, 229]
  1. aAA and ANA: AA (Alko, Alcohol) line of rats which prefer 10 % alcohol to water, and the ANA (Alko, Non-Alcohol) line of rats which are given only water
  2. bAPP-C99: an amyloid precursor protein fragment