Table 2

Glyceollins effects in noncancer diseases.

Diseases or FunctionsCell Line/Animal ModelTreatmentMajor EffectsReferences
OsteoporosisAdipose-derived stromal cells and bone marrow stromal cell lineGI 1 and GII 2- GI and GII: Increase calcium deposition
- GII: Stronger than E2 and GI, increase the expression of genes involved in osteogenic differentiation in a similar manner to E2
Bateman et al. 2017 [76]
Glucose and lipid metabolismEnteroendocrine NCI-H716 cell lineGlyceollin mixture 3- Enhance GLP-1 4 secretion to increase insulinotropic actionsPark et al. 2010 [79]
3T3-L1 adipocyte cell lineGlyceollin mixture- Increase both insulin-stimulated and basal glucose uptake
- Increase glucose transporter GLUT4 5 level
- Decrease triacylglycerol accumulation
Boué et al. 2012 [41], Park et al. 2010 [79]
Insulima Min6 cell lineGlyceollin mixture- Decrease apoptosis
- Enhance insulinotropic actions
Park et al. 2010 [79]
Diabetic male C57BL6J mouseFermented soybeans containing glyceollins- Decrease blood glucose level
- Increase hepatic glycogen accumulation
- Decrease triglyceride storage
Park et al. 2012 [42]
Prediabetic male ZDSD/Pco ratGlyceollin mixture- Decrease blood glucose levelBoué et al. 2012 [41]
Male golden Syrian hamsterDiet containing glyceollins- Reduce plasma VLDL 6, hepatic cholesterol esters, total lipid content
- Alter expression of the genes related to cholesterol in liver
Huang et al. 2013 [80]
Female monkey (Macaca fascicularis)Diet containing glyceollins- Decrease serum total cholesterol, specifically LDL 7 and VLDL, increase serum triglycerides
- Upregulate genes expression of PPAR 8-γ, adiponectin, leptin, liptin 1, lipoprotein lipase and triglyceride
Wood et al. 2012 [81]
Oxidative stressTests in vitroGlyceollin mixture- Have ferric-reducing antioxidant power, radical scavenging activitiesKim et al. 2010 [82]
Hepa1c1c7/ BPRc1 cell lineGlyceollin mixture- Inhibit H2O2-induced ROS 9 production
- Induce Nrf2-mediated phase 2 detoxifying enzymes
- Activate Nrf2-signaling pathway under oxidative stress
Kim et al. 2010 [82], Kim et al. 2011 [83]
Jung et al. 2013 [84]
Female C57BL/6J mouseGlyceollin mixture- Increase NAD(P)H:quinone oxidoreductase 1activity in kidney, liver, and large intestineKim et al. 2015 [72]
RatGlyceollin mixture- Inhibit lipid peroxidation in liver, kidney, and brain tissue extractsKim et al. 2010 [82]
Central nervous systemBreast cancer MCF-7 cell lineGlyceollins mixture- Increase nerve growth factor receptor gene expressionZimmermann et al. 2010 [28]
Glutamate-sensitive murine hippocampal HT22 cell lineGlyceollin mixture- Attenuate glutamate-induced neurotoxicity
- Suppress glutamate-induced intracellular ROS
- Act through Nrf2 signaling pathway, activate hem oxygenase-1 enzyme
Seo et al. 2018 [85]
Primary cortical neurons from wild-type and Nrf2 knockout male C57BL/6J mouseGlyceollin mixture- Suppress glutamate-induce cytotoxicity in primary cortical neurons of wild-type mice, but not cells from Nrf2 knockout.Seo et al. 2018 [85]
Wild-type and Nrf2 knockout male C57BL/6J mouseGlyceollin mixture-Improve cognitive deficits caused by scopolamine in wild-type mice, but no effect in Nrf2 knockout mice
- Inhibit acetylcholine esterase activity in neurons from the cortex, but not in cells from the hippocampus
Seo et al. 2018 [85]
Ovariectomized adult female CFW mouseGlyceollin mixture- Upregulate genes involved in neurogenesis, synaptic plasticity, tissue development and transcripts involved in signal transduction pathways, regulation of nerve impulse, cytoskeletal remodeling, and hormone signaling
- Downregulate genes involved in neurodegeneration apoptosis and transcripts involved in developmental neurogenesis, synaptogenesis, and cell adhesion
- Act through ER 10-dependent or ER-independent mechanisms depending on the target genes
Bamji et al. 2015 [86], Bamji et al. 2018 [87]
Inflammation Murine macrophage RAW264.7 cell lineGlyceollin mixture - Inhibit nitric oxide production and inflammatory mediators release through the NF-κB pathwayKim et al. 2011 [88], Yoon et al. 2012 [89]
Human umbilical vein endothelial cell lineGlyceollin mixture- Reduce HMGB1 11 protein level induced by LPS 12
- Decrease HMGB1-induced vascular barrier disruption
- Decrease HMGB1-mediated pro-inflammatory and inflammatory response
Lee et al. 2014 [90]
ICR mouseGlyceollin mixture- Reduce mouse ear swelling caused by 12-O-tetradecanoylphorbol-13-acetate Kim et al. 2011 [88]
Male C57BL/6 mouse that underwent cecal ligation and punctureGlyceollin mixture- Reduce serum HMGB1 level, decrease HMGB1-induced vascular barrier disruption
- Reduce HMGB1-induced mortality
Lee et al. 2014 [90]
Cardiovascular diseasesHuman aortic smooth muscle cell lineGlyceollin mixture- Inhibit the cell proliferation and migration induced by PDGF-BB 13Kim et al. 2012 [91]
Aortic rings from male Sprague-Dawley ratGI- Reduce vascular contraction partly through the inhibition of the RhoA/Rho-kinase signaling pathwaySong et al. 2010 [92]
MelanogenesisB16/B16F10 cell linesGlyceollin mixture- Inhibit melanin synthesis by decreasing melanogenic enzymes and other factorsLee et al. 2010 [93], Shin et al. 2013 [94]
Standard AB strain zebrafish (Danio rerio) embryosGlyceollin mixture- Decrease the pigmentation of the embryos, melanin synthesis and tyrosinase activity
- Decrease Sox10, a pigment cell-specific gene
Shin et al. 2013 [94]
1 Glyceollin I, 2 Glyceollin II, 3 Glyceollin mixture contains glyceollin I, glyceollin II, and glyceollin III, 4 glucagon-like peptide 1, 5 glucose transporter 4, 6 very low-density lipoprotein, 7 low-density lipoprotein, 8 peroxisome proliferator-activated receptor, 9 reactive oxygen species, 10 estrogen receptor, 11 high mobility group box 1, 12 lipopolysaccharide, 13 platelet-derived growth factor BB.