Table 6.
Condiments or ingredients in drinks modulate PI3K/Akt and/or GSK3 activities
| 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. | [207–209] |
| 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. | [210–212] |
| 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. | [219–221] | |
| 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. | [223–225] |
| 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] |
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
bAPP-C99: an amyloid precursor protein fragment