19 February 2024: Review Articles
Resibufogenin: An Emerging Therapeutic Compound with Multifaceted Pharmacological Effects – A Comprehensive Review
Hao Zhang 1AEG , Baiyu Jian 2AG*DOI: 10.12659/MSM.942783
Med Sci Monit 2024; 30:e942783
Table 1 Pharmacological effects of resibufogenin: summary of in vitro and in vivo studies.
| Pharmacological action | Experimental model | Activity | Mechanisms | References |
|---|---|---|---|---|
| Anticancer | Human gastric cancer cells 803 | 4 and 8 μM RBG (24 and 48 h)inhibits the viability.8 μM RBG (12 h) inhibits the viability | Inhibits cell viability, and induces apoptosis by suppressing the PI3K/AKT/GSK3β signaling pathway | []9 |
| Human multiple myeloma cells RPMI8226 | IC=7.694 μM (48 h) | Inhibits viability, migration, invasion, and EMT, and promotes the apoptosis of multiple myeloma cells by blocking the PI3K/AKT signaling pathway | []10 | |
| Human colon cancer HT-29 cells | RBG at a concentration of 5 μM inhibits cell proliferation | Inhibits colorectal cancer cell growth and tumorigenesis through triggering ferroptosis and ROS production mediated by GPX4 inactivation | []11 | |
| Human colon cancer SW480 cells | RBG at a concentration of 5 μM inhibits cell proliferation | |||
| Normal colonic epithelial cells NCM460 | 20 μM of RBG can inhibit the proliferation of NCM460 cells | |||
| Nude mice bearing human colorectal cancer SW480 | 40 and 80 mg/kg RBG were injected into tumor tissues per day until the tumor volume reached about 100 mm. The results showed that RBG inhibited tumor growth, but had little impact on mice body weight | |||
| Human colon cancer HT-29 cells | 2 μM or more RBG for 2 and 3 days significantly inhibits the viability | Induces G1-Phase arrest through the proteasomal degradation of cyclin D1 in human malignant tumor cells | []12 | |
| Nude mice bearing human colorectal cancer SW480 | 5 and 10 mg/kg/day RBG (intraperitoneal injection) in mice for 21 days, the weight of the tumor in situ was significantly reduced by 27 and 41%, respectively | Retards tumor growth and metastasis by activating RIP3 and subsequently phosphorylating MLKL which leads to necroptosis. | []13 | |
| Human colorectal cancer HCT-116 | Inhibits the viability | |||
| Human glioblastoma stem-like cells P3#GBM | IC=2.29 μM | Binds to ATP1A1, Na±K±ATPase is activated as a receptor and then triggers the intracellular MAPK/ERK pathway and Ca-mediated Src/FAK/Paxillin focal adhesion pathway, which leads to G2/M phase arrest and inhibited the invasion of glioblastoma cells | []14 | |
| Human glioblastoma cells U251 | IC=3.05 μM | |||
| Human glioblastoma cells A172 | IC=6.21 μM | |||
| Normal human astrocyte cells | IC=32.66 μM | |||
| Nude mice bearing human glioblastoma cells P3#GBM | 10 mg/kg/day RBG (intraperitoneal injection), on the 21 day after implantation, the tumor weight decreased | |||
| Human umbilical vein endothelial cell | IC=3 μM | Inhibits the proliferation, migration, and tube formation of human umbilical vein endothelial cells and inhibits angiogenesis in matrigel plugs in vivo by blocking VEGFR2-mediated signaling pathway | []15 | |
| Anti-inflammatory | Endotoxemia mice | Possesses nonnegligible anti-inflammatory activity | Possesses anti-inflammatory activity in vitro and in vivo by suppressing both NF-κB and MAKPs/AP-1 pathways | []16 |
| Murine macrophage cells RAW264.7 and Mouse peritoneal macrophages MPMs | RBG exerts anti-inflammatory activity in both of them, its effect in RAW264.7 cells is stronger than that in MPMs | |||
| Antiviral | Anti-enterovirus 71 | IC=218 nmol/L | [–]17 | |
| Anti-Middle East Respiratory Syndrome Coronavirus infection in Vero cells | IC=1.612 μM | []17 | ||
| Anti-middle east respiratory syndrome coronavirus infection in Calu-3 human lung cells | IC=15.970 μM | |||
| Cardiotonic effect | Rabbits | Increases ventricular contractile force by approximately 34% | [,]8 | |
| Cats | Increase ventricular contractile force by approximately 36% | |||
| Adult mongrel dogs | Increases ventricular contractile force by approximately 32–50% | |||
| Respiratory center | Rabbits | Increases respiratory amplitude, tidal volume, and minute volume | []20 | |
| Blood pressure | A hemorrhaged animal model | Increases systemic arterial pressure | Enhances cardiac output without markedly affecting heart rate. And RBG exerts a peripheral vasoconstrictor action | []20 |
| Deoxycorti-costerone acetate salt hypertensive rats | RBG reduces the blood pressure | Reduces superoxide generation in deoxycorticosterone acetate salt hypertension | []21 |