Licorice (Glycyrrhiza glabra) has been largely used for thousands of years in traditional Chinese medicine. Licorice and its derived compounds possess antiallergic, antibacterial, antiviral, anti-inflammatory, and antitumor effects. G is a triterpene glycoside complex and has been shown to possess cytotoxic effects against several cancer cell lines such as colon, lung, leukemia, melanoma, and glioblastoma (GBM). GA, an aglycone of G, has been demonstrated to have pro-apoptotic effects on human hepatoma, promyelocytic leukemia, stomach cancer, Kaposi sarcoma-associated herpesvirus-infected cells, and prostate cancer cells in vitro by inducing DNA fragmentation and oxidative stress.
Model | Compound (Dose) | Mechanism | Reference |
---|---|---|---|
In vitro (KATO III and HL-60) | G (1 to 10 mg/mL) | Antitumor activity ↑ apoptosis | [23] |
In vitro (HLE, KATO III, and HL-60) | G (0.1 to 1 mg/mL) | Antitumor activity ↑ apoptosis | [24] |
In vitro (DU-145 and LNCaP) |
G (1 to 20 mM) | Antitumor activity ↑ apoptosis | [25] |
In vitro (Caco3, HT29, and RAW 264.7) In vivo (Acute lung injury mice model) |
DPG (300 µM) DPG (3 and 8 mg/kg/day) |
↓ TNF-α, IL-1β, and IL-6, as well as HMGB1 receptors, RAGE and TLR4 | [34] |
In vitro (neutrophils) | G (0.05, 0.5, and 5.0 µg/mL) | ↓ ROS | [38] |
In vivo (Con A-induced hepatitis) Ex vivo (liver dendritic cells) |
G (2 mg/mouse) G (0.1 mg/mL) |
↑ IL-10 and ↓ liver inflammation | [39] |
In vitro (U251) | GA (1, 2, 4 mM) | Anticancer effect ↓ proliferation and ↑ apoptosis possibly related to the NF-κB mediated pathway | [40] |
In vitro (U87MG and T98G) | DPG (0.1 to 2 mM) | Anticancer effect ↓ proliferation and ↑ apoptosis. ↓ NF-κB pathway | [46] |
In vivo (DSS-induced colitis mice model) | DPG (8 mg/kg/day) | ↓ colitis, at the earlier stages, ↓ inflammation though AMPK-COX-2-PGE. At later times ↓ iNOS and COX-2 in HMGB1-dependent manner | [49] |
In vivo (mechanical thrombectomy rat model) | G (2, 4 and 10 mg/kg/day) | ↓ HMGB1 and its downstream inflammatory factors, and ↓ oxidative stress |
[50] |
In vivo (Focal cerebral I/R injury rat model) | G (4 mg/kg/day) | ↓ HMGB1 and ↑ apoptosis through the blockage of the JNK and p38 | [51] |
In vivo (Sepsis-induced acute lung injury rat model) | G (25 and 50 mg/kg/day) | ↓ inflammatory responses, oxidative stress damage, and apoptosis though ↓ NF-κB, JNK, and p38 MAPK |
[52] |
In vivo (Acute lung injury mice model) | G (20 and 40 mg/kg/day) | ↓ LPS-induced lung injury via blocking HMGB1/TLRs/NF-κB pathway | [53] |
In vitro (RAW 264.7 and bone marrow monocytes) | G (25 to 100 µM) | ↓ RANKL-induced osteoclastogenesis and oxidative stress through ↑ AMPK/Nrf2 and ↓ NF-κB and MAPK | [56] |
In vivo (Parkinson rat model) | GA (50 mg/kg/day) | ↓ dopamine neuron loss and ↓ Iba-1 and GFAP ↑ antioxidant enzyme activity, ↓ lipid peroxidation, ↓ pro-inflammatory cytokines |
[58] |
In vivo (Vascular dementia rat model) | GA (20 mg/kg/day) | ↓ release of cytochrome-c and ↑ Bcl2, and ↑ the endogenous antioxidants |
[59] |
In vitro (HBZY-1) In vivo (sepsis-induced acute kidney injury mice model) |
GA (50 and 100 µM) GA (25 and 50 mg/kg/day) |
↓ oxidative stress via ↑ ERK signaling pathway. ↓ NF-κB | [60] |
In vivo (myocardial ischemic injury-rat model) | GA (10 and 20 mg/kg/day) | ↓ oxidative stress and inflammatory cytokines. ↑ Nrf2 antioxidant response ↓ NF-κB activation |
[61] |
In vitro (HEPG2) | G (5, 25 and 125 µg/mL) | ↓ H2O2-induced oxidative stress, ↑ apoptosis | [62] |
In vitro (HT29) | GA (1, 5 and 10 µM) | ↓ TNF-α-mediated IL-8 through ↓ MAPK and the IKB/NF-κB pathway | [63] |
In vivo (DSS-induced colitis mice model) | GA (10 and 50 mg/kg/day) | ↓ colitis, ↓ inflammation by regulating COX-2 and NF-κB | [64] |
In vivo (rat model of ulcerative colitis) | G (40 mg/kg/day) | ↓ colitis, ↓ inflammatory injury via suppression of NF-κB, TNF-α, and ICAM-1 |
[65] |
In vivo (TNBS-induced experimental colitis mice model) | G (10, 30 and 90 mg/kg/day) | ↓ colitis, ↓ IFN-γ, IL-12, TNF-α, and IL-17 and ↑ IL-10 | [66] |
In vivo (DSS-induced colitis rat model) | G (2 mg rectally) | ↓ colitis, ↓ IL-1β, IL-6, TNF-α, Cxcl-2, Mcp1, and MPO | [67] |
In vivo (TNBS-induced experimental colitis rat model) | GA (2, 10 and 50 mg/kg, rectally and 10 mg/kg/day) | ↓ colitis, ↓ serum levels of TNF-α and IL-1β, ↓ colon MPO and MDA, and ↑ SOD | [68] |
In vivo (rat model of ulcerative colitis) | G (100 mg/kg/day) | ↓ colitis, when combined with emu synergistically ↓ of PPARγ and TNF-α | [69] |
In vivo (TNBS-induced experimental colitis mice model) | G (50 mg/kg/day) | ↓ colitis, ↓ HMGB1 on DC/macrophage mediated Th17 proliferation | [70] |
In vivo (indomethacin-induced small intestinal injury mice model) | GA (100 mg/kg/day) | ↓ TNF-α, IL-1β, and IL-6, ↑ indomethacin-induced small intestinal damage | [71] |
In vivo (DSS-induced colitis mice model) | G (100 mg/kg/day) | ↓ colitis, regulated the phosphorylation of transcription factors such as NF-κB p65 and IκB α | [72] |
In vivo (DSS-induced colitis mice model) | DPG (8 mg/kg/day) | ↑ mucosal healing by ↓ CXCL1, CXCL3, CXCL5, PTGS2, IL-1β, IL-6, CCL12, CCL7; ↑ wound healing genes COL3A1, MMP9, VTN, PLAUR, SERPINE, CSF3, FGF2, FGF7, PLAT, TIMP1 and ↑ extracellular matrix remodeling genes, VTN, and PLAUR |
[73] |
This entry is adapted from the peer-reviewed paper 10.3390/ijms23084121