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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 actionExperimental modelActivityMechanismsReferences
AnticancerHuman gastric cancer cells 8034 and 8 μM RBG (24 and 48 h)inhibits the viability.8 μM RBG (12 h) inhibits the viabilityInhibits cell viability, and induces apoptosis by suppressing the PI3K/AKT/GSK3β signaling pathway[]9
Human multiple myeloma cells RPMI8226IC=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 cellsRBG at a concentration of 5 μM inhibits cell proliferationInhibits colorectal cancer cell growth and tumorigenesis through triggering ferroptosis and ROS production mediated by GPX4 inactivation[]11
Human colon cancer SW480 cellsRBG at a concentration of 5 μM inhibits cell proliferation
Normal colonic epithelial cells NCM46020 μM of RBG can inhibit the proliferation of NCM460 cells
Nude mice bearing human colorectal cancer SW48040 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 cells2 μM or more RBG for 2 and 3 days significantly inhibits the viabilityInduces G1-Phase arrest through the proteasomal degradation of cyclin D1 in human malignant tumor cells[]12
Nude mice bearing human colorectal cancer SW4805 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%, respectivelyRetards tumor growth and metastasis by activating RIP3 and subsequently phosphorylating MLKL which leads to necroptosis.[]13
Human colorectal cancer HCT-116Inhibits the viability
Human glioblastoma stem-like cells P3#GBMIC=2.29 μMBinds 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 U251IC=3.05 μM
Human glioblastoma cells A172IC=6.21 μM
Normal human astrocyte cellsIC=32.66 μM
Nude mice bearing human glioblastoma cells P3#GBM10 mg/kg/day RBG (intraperitoneal injection), on the 21 day after implantation, the tumor weight decreased
Human umbilical vein endothelial cellIC=3 μMInhibits 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-inflammatoryEndotoxemia micePossesses nonnegligible anti-inflammatory activityPossesses 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 MPMsRBG exerts anti-inflammatory activity in both of them, its effect in RAW264.7 cells is stronger than that in MPMs
AntiviralAnti-enterovirus 71IC=218 nmol/L[–]17
Anti-Middle East Respiratory Syndrome Coronavirus infection in Vero cellsIC=1.612 μM[]17
Anti-middle east respiratory syndrome coronavirus infection in Calu-3 human lung cellsIC=15.970 μM
Cardiotonic effectRabbitsIncreases ventricular contractile force by approximately 34%[,]8
CatsIncrease ventricular contractile force by approximately 36%
Adult mongrel dogsIncreases ventricular contractile force by approximately 32–50%
Respiratory centerRabbitsIncreases respiratory amplitude, tidal volume, and minute volume[]20
Blood pressureA hemorrhaged animal modelIncreases systemic arterial pressureEnhances cardiac output without markedly affecting heart rate. And RBG exerts a peripheral vasoconstrictor action[]20
Deoxycorti-costerone acetate salt hypertensive ratsRBG reduces the blood pressureReduces superoxide generation in deoxycorticosterone acetate salt hypertension[]21

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750