Table 1.
The Biological Effects of Glabridin in Different Models
| Category | Models | Biological Effects | Ref. |
|---|---|---|---|
| Anti-inflammation | J774A.1 and HL-60 (exposing to 0.62, 1.25, 2.5, 5, and 10 μg/mL glabridin) | Inhibits the expression of PGE2 (IC50 = 11 μM), TXB2 (IC50 = 11.3 μM), and LTB4 (IC50 = 5.3 μM) | [26] |
| Male Wistar rats receive 30 mg/kg glabridin by intraperitoneal injection | Inhibits the activity of p38MPAK/ERK signaling | [28] | |
| J774A.1 cells were treated with 0.62, 1.25, 2.5, 5, and 10 μg/mL glabridin | Decreases 33% of the NO level and inhibits IL-1β production with an IC50 value of 30.8 μM | [27] | |
| LPS-treated RAW264.7 cells were exposed to 0.3, 1, 3, and 10 μM glabridin | Inhibits the activity of NF-κB signaling | [29] | |
| LPS-treated THP-1 cells were exposed to 100 nM glabridin | Suppresses iNOS expression and nitrotyrosine formation | [31] | |
| LPS-treated HaCat cells were exposed to 5 and 10 μM glabridin | Decreases the activity of TLR4/MyD88/NF-κB signaling | [32] | |
| Inhibits iNOS/NO, p65, IL-6, and IL-1β expression and decreases IL-17A, IL-22, and IL-23 expression | [33] | ||
| LPS-treated DCs were exposed to 5, 10, 15, and 20 μM glabridin | Inhibits NF-κB and MAPK signaling pathways | [36] | |
| Anti-oxidation | MPMs, J-774A.1 (20 μM glabridin) | Inhibits 80% of cell-based LDL oxidation, 60% of superoxide release, and P47 translocation | [39] |
| Male ApoE−/− mice receive 40 mg/kg/day glabridin in the drinking water for 2 months | Increases GSH accumulation and reduce lipid peroxides production | [40] | |
| High glucose-treated THP-1 cells were exposed to 100 nM glabridin | Increases the expression of CAT, PON2, and Mn-SOD | [41] | |
| Docking | Interacts with rePON1 and prevents from LA-OOH-induced oxidation | [43] | |
| Male SD rats with MCAO receive 5 and 25 mg/kg glabridin by intraperitoneal injection for 7 days | Ameliorates the focal infarct volume, histopathological changes, and cell apoptosis | [44] | |
| NHK cells were exposed to 15 μM glabridin | Prevents against UVB-induced DNA damage and cell apoptosis | [45] | |
| Fluorescence quenching | Inhibits tyrosinase activity with an IC50 value of 0.43 μM | [46] | |
| Anti-tumor | MDA-MB-231, Hs578T and Hepatocarcinoma were exposed to 10 μM glabridin | Induces miR-148a gene demethylation and its expression, inhibits the expression of SMAD2, and attenuates the CSC-like properties | [47] |
| MDA-MB-231 and Hs578T cells were exposed to 10 and 20 μM glabridin | Down regulates miR-148/Wnt/β-catenin activity and its downstream factor VEGF expression | [50] | |
| SK-BR-3 cells were exposed to 10, 50, and 100 μM glabridin | Increases the protein expression of c-PARP, cleaved-caspase-3, caspase-8, and caspase-9; decreases p-ERK1/2, p-AKT, p-EGFR, and cyclin D1 expression | [51] | |
| Ishikawa cells were exposed to 10 μM glabridin | Promotes estrogen responsive genes expression | [52] | |
| Ishikawa cells were exposed to 100 pM, 1 nM, 10 nM, 100 nM, 1 μM, and 10 μM glabridin | Increases ERα-SRC-1-co-activator signaling | [53] | |
| Ishikawa cells were exposed to 1 μM glabridin | Modulates the expression ESR1 and Bcl-2 | [54] | |
| SCC-9 cells were exposed to 20, 40, and 80 μM glabridin | Inhibits cell proliferation, causes cell cycle arrest, and increases the activity of p38 MAPK and JNK1/2 signaling | [55] | |
| MN-45 cells were exposed to a combination of 0.1 mM 5-FU and 25 μM glabridin | Inhibits cell survival, proliferation, and invasion | [56] | |
| A549 (1, 2.5, 5, and 7.5μM glabridin), MDA-MB-231 (2.5, 5, 7.5, and 10 μM glabridin) | Inhibits cell migration, invasion, and angiogenesis. Increases αvβ3 integrin degradation, decreases FAK and Src interaction, and reduces AKT and RhoA activation | [57,58] | |
| HepG2 cells were exposed to 15, 30, and 45 μM glabridin | Down regulates the expression of cyclinD3, CDK2, and CDK4 and inhibits Braf/MEK signaling | [59] | |
| Huh7 cells were exposed to 25, 50, and 100 μM glabridin | Activates the expression of p38 MAPK and JNK1/2 signaling | [60] | |
| MG63 and HOS cells were exposed to 5, 10, and 25 μM glabridin | Decreases the expression of MMP-2 and MMP-9, and induce cell cycle arrest | [63] | |
| Anti-microorganism | Docking | Inhibits Mpro with the binding affinity of −8.1 kcal/mol | [19] |
| Binds to 3CLpro with a binding energy of −8.25 kcal/mol by forming hydrogen bonds with Glu166, Arg188, and Gly143 | [65] | ||
| Vero E6 were exposed to 3.1, 6.2, 12.5, 25, and 50 μM glabridin | Protects against SARS CoV-2 with an IC50 value of 2.5 μM | [138] | |
| Docking | Inhibits NS3 protease with binding affinity of −7.4 kcal/mol | [67] | |
| S. aureus were treated with 1/4 MIC, 1/2MIC, and MIC of glabridin (MIC=12.5 μg/mL) | Increases the productions of ROS, NO, and MDA and decreases the expression of SOD | [69] | |
| MRSA 4423 were treated with 1/16, 1/8, 1/4, and 1/2MIC of glabridin | Down regulates the expression of cell surface proteins | [70] | |
| MRSA 4427 were treated with 1MIC of glabridin | Increases ROS production and induces oxidative stress | [139] | |
| E. faecalis | At the dose of 25 μg/mL, it is active for 11.2% killing | [71] | |
| Combination of glabridin (25 μg/mL) with nisin (12.5 μg/mL) produces 61.4% killing | [72] | ||
| H37Ra, H37Rv | Inhibits with a MIC value of 29.16 μg/mL | [73] | |
| C. albicans | Inhibits ATCC 28366 and LAM-1 with MIC values of 6.25 μg/mL and 12.5 μg/mL, respectively. | [76] | |
| Promotes MCA1 and NUC1 expression, increases apoptosis | [77] | ||
| C. glabrata | Decreases the MIC values against fluconazole-resistant (MIC50 = 8 μg/mL), promotes apoptosis, and induces the expression of MCA1 and NUC1 | [80] | |
| F. graminearum | Inhibits the mycelial growth and conidial germination with EC50 values of 110.70 mg/L and 40.47 mg/L, respectively. | [84] | |
| E. tenella | Inhibits the replication of by 75%, 50%, and 30% at the doses of 21.43 μg/mL, 5.28μg/mL, and 0.96μg/mL, respectively. | [86] | |
| Bone protection | RAW264.7 cells were exposed to 1, 2, and 5 μM glabridin | Increases the activity of TRAF6, GAB2, ERK2, JNK1, and MKK7, enhances the expression of c-FOS and NFATc1, and elevates the productions of MMP-9, cathepsin K, CAII, TCIRG1, OSTM1, and CLCN7. | [87] |
| C2C12 cells were exposed to 10 μM glabridin | Abolishes dexamethasone-stimulated protein degradation | [88] | |
| L6 myotubes were exposed to 3, 10, and 30 μM glabridin | Stimulates AMPK-dependent GLUT4 translocation | [89] | |
| MC3T3-E1 cells were exposed to 0.01, 0.1, and 1 μM glabridin | Inhibits MG-induced cytotoxicity and cell death | [90] | |
| MC3T3-E1 cells were exposed to 5 μM glabridin | Ameliorates dRib-induced oxidative damage and increases ALP, OPN, OPG, OC, and BMPs expression by up regulating the expression of PI3K/AKT2 signaling pathway | [91] | |
| MSCs were exposed to 1, 10, and 50 μM glabridin | Increases the expression of Oct4, Dlx5, Runx5, Osteocalcin, and Osteopontin | [96] | |
| Cardiovascular protection | Male New Zealand Rabbits receive 2 mg/kg glabridin by oral catheter for 6 weeks | Down regulation of MLCK/phosphorylated MLC system through MAPK signaling | [21] |
| ECV-304 cells were exposed to 30 and 3000 nM glabridin | Increases DNA synthesis, exhibits a bi-phasic effect on the proliferation of VSMC | [100] | |
| Colonic macrophages from DOX-treated male C57BL/6 mice were exposed to 15 and 30 μM glabridin | Prevents against DOX-induced dysbiosis by modulating LPS/NF-κB and butyrate-STAT6 signaling | [101] | |
| Hepato-protection | Male Swiss Mice receive 10–40 mg/kg glabridin intraperitoneally | Increases NRF2 expression, decreases NF-κB signaling | [22] |
| Male Wistar rats receive diets supplemented with glabridin (40 mg/kg) for 8 weeks | Decreases STZ-induced collagen fiber deposition, ameliorates microvascular abnormality and liver fibrosis | [103] | |
| HepG2 were exposed to 20 and 100 μM glabridin | Interacts with the LBD of PPARγ (EC50 = 6115 nM) | [104] | |
| Docking | Acts as an inhibitor and binds to CYP2E1 with -CDOCKER interaction energy of −84.44 kcal/mol | [106] | |
| Neuro-protection | LPS-treated BV-2 cells were exposed to 0.3, 1, 3, and 10 μM glabridin | Decreases the productions of IL-1β, TNFα, and NO by down regulating the activity of NF-κB signaling and AP-1 | [23] |
| Male Kunming mice receive 1, 2, and 4 mg/kg orally | Improves memory, reduces the brain cholinesterase activity | [110] | |
| Electrophysiology | Potentiates GABAA α1β(1–3)γ2 receptor activity, decreases the EC50 values of the receptor for GABA by about 12 folds | [113] | |
| Anti-obesity | 3T3-L1 cells were treated with 25 and 50 μM glabridin | Inhibits adipogenesis by decreasing the expression of C/EBPα and PPARγ | [24] |
| 3T3-L1 cells were treated with 5, 10, and 20 μM glabridin | Inhibits the generation of ROS, PGE2, PLA2, COX-1, and intracellular Ca2+ concentrations, increases the expression of insulin receptor substrate 1 and Glut4 | [122] | |
| Anti-diabetes | Male SD rats receive 50 mg/kg glabridin by intraperitoneal injection for 28 days | Increases the productions of Scr, BUN, UREA, KIM-1, NGAL, and TIMP-1 | [127] |
| High glucose-treated NRK-52E cells were exposed to glabridin | Suppresses ferroptosis by suppressing oxidative stress and decreasing VEGF, p-AKT, and p-ERK1/2 expression | [127] |