Jujuboside B

Jujuboside B is a bioactive saponin component isolated from Ziziphi Spinosae Semen (sour jujube seed), with oral efficacy and blood-brain barrier permeability. Jujuboside B induces acute leukemia cell death and drives necroptosis apoptosis by activating the RIPK1/RIPK3/MLKL pathway. Jujuboside B upregulates the expression of NOXA, PARP and caspase-3, activates AMPK, inhibits the proliferation of breast cancer cells, and induces cell apoptosis and autophagy. Jujuboside B inhibits angiogenesis and tumor growth by blocking the VEGFR-2 signaling pathway. Jujuboside B alleviates liver injury in mice by regulating the Nrf2-STING signaling pathway. Jujuboside B alleviates liver injury by regulating anti-inflammatory responses and downregulating the expression of 11β-HSD2. Jujuboside B induces ferroptosis and overcomes radioresistance in non-small cell lung cancer via the PPARγ-ATF3-Gpx4 signaling pathway. Jujuboside B exerts inhibitory effects on platelet aggregation. Jujuboside B inhibits febrile seizures by suppressing the activity of AMPA receptors. Jujuboside B reverses chronic unpredictable mild stress-promoted tumor progression by blocking the PI3K/Akt and MAPK/ERK pathways and dephosphorylating CREB signaling. Jujuboside B is applicable to related studies on acute leukemia, breast cancer, PM_2.5-induced lung injury, hepatotoxicity, liver injury, colorectal cancer, non-small cell lung cancer, thromboembolic diseases, cardiovascular diseases associated with high platelet aggregation, febrile seizures, and depressive-like phenotypes^{[1][2][3][4][5][6][7][8][9][10]}. In Vitro:Jujuboside B (40-200 μM; 24-72 h) reduces the viability of acute leukemia cell lines U937, HL-60, Jurkat and Kasumi-1 in a dose- and time-dependent manner, and decreases the survival rate of primary human acute myeloid leukemia (AML) cells^[1].
Jujuboside B (0-120 μM; 2 weeks) significantly reduces the clonogenic capacity of U937 acute leukemia cells^[1].
Jujuboside B (40-120 μM; 24 h) mediates necroptosis of U937 acute leukemia cells via the RIPK1/RIPK3/MLKL pathway, and upregulates the total and phosphorylated protein levels of RIPK1, RIPK3 and MLKL in U937 acute leukemia cells^[1].
Jujuboside B (20-100 μM; 72 h) potently inhibits the proliferation of human breast cancer cells MDA-MB-231 (IC₅₀ = 54.38 μM) and MCF-7 (IC₅₀ = 74.94 μM) after a 72 h treatment^[2].
Jujuboside B (25-75 μM; 10-14 days) reduces the clonogenic survival rate of MDA-MB-231 and MCF-7 human breast cancer cells^[2].
Jujuboside B (25-75 μM; 16-48 h) dose-dependently inhibits the migration of human breast cancer MDA-MB-231 cells, induces dose-dependent apoptosis in human breast cancer MDA-MB-231 and MCF-7 cells, upregulates the expressions of apoptosis markers cleaved PARP and cleaved caspase-3 in human MDA-MB-231 and MCF-7 cells, upregulates NOXA expression in MDA-MB-231 and MCF-7 cells, and activates AMPK^[2].
Jujuboside B (25-75 μM; 12-48 h) induces dose-dependent and time-dependent autophagy in human breast cancer cell lines MDA-MB-231 and MCF-7, enhances the conversion of LC3-I to LC3-II, and reduces the expression level of p62. It induces autophagy in an AMPK-dependent manner in human breast cancer MCF-7 cells^[2].
Jujuboside B (1-100 μM; 8-48 h) dose-dependently inhibits cell viability, migration, and Matrigel-based tube formation of HUVECs, while exerting minimal effects on the viability of HCT-15 cells^[6].
Jujuboside B (1-100 μM; 24 h) dose-dependently arrests HUVECs at the G0/G1 phase of the cell cycle^[6].
Jujuboside B (1-100 μM; 30 min pre-incubation) dose-dependently blocks VEGF₁₆₅-induced phosphorylation of VEGFR2 and its downstream mediators (Akt, FAK, Src, PLCγ1) in HUVEC^[6].
Jujuboside B (100 μM; 24 h) exerts better regulatory effects on the protein levels of DR4 and DR5 at 100 ng/mL in A549 and H460 cells than the single treatment^[7].
Jujuboside B (30-300 μM; 5 min) dose-dependently inhibits collagen-, thrombin-, Arachidonic acid (AA) (HY-109590)- and adenosine diphosphate (ADP)-induced platelet aggregation in rat platelet-rich plasma, with IC₅₀ values of 92.1 μM, 201.5 μM and 95.2 μM for collagen-, thrombin- and AA-induced aggregation, respectively, and exhibits no platelet cytotoxicity at the concentration of 300 μM^[8].
Jujuboside B (30-300 μM; 5 min pre-treatment followed by 6 min incubation with collagen) dose-dependently inhibits collagen-induced TXA₂ production in rat platelet-rich plasma^[8].
Jujuboside B (30-100 μM) inhibits the currents of recombinant GluA1/GluA2 AMPA receptors in HEK293 cells in a dose-dependent manner in vitro^[9].
Jujuboside B (pre-incubated for 1 min prior to AMPA stimulation at a concentration of 10 μM) significantly inhibits AMPA-induced intracellular calcium elevation in primary cultured rat cortical neurons, and reduces the peak and cumulative values of calcium responses^[9].
Jujuboside B (20-100 μM; 60 μM for viability, colony formation, pathway analysis) inhibits the viability and colony formation of A549 cells, and blocks the PI3K/Akt and MAPK/ERK signaling pathways by reducing the phosphorylation levels of key pathway components, with an IC₅₀ of 60 μM^[10]. In Vivo:Jujuboside B (i.p.; once daily; for 17 consecutive days; 20 mg/kg) significantly inhibits the growth of MCF-7 and MDA-MB-231 breast cancer xenografts in nude mice, while inducing tumor cell apoptosis and autophagy, with no observed effect on animal body weight^[2].
Jujuboside B (0.1-0.8 mg/kg; i.v.; 3 times within 2 days) significantly alleviates PM_2.5-induced lung injury in BALB/c mice by regulating the TLR2/4-MyD88 and mTOR-autophagy pathways to reduce inflammation, apoptosis and autophagy dysfunction^[3].
Jujuboside B (i.p./i.v.; once daily; consecutive 7 days/single administration, 20-40 mg/kg/0.4-1.5 mg/kg) dose-dependently ameliorates Acetaminophen (HY-66005)-induced acute liver injury in male C57BL/6 J mice, while inhibiting oxidative stress, inflammatory response, cell apoptosis and STING pathway activation, and activating the Nrf2 pathway. It also dose-dependently protects male C57BL/6 mice from cecal ligation and puncture (CLP)-induced liver injury by alleviating inflammation, enhancing antioxidant capacity, upregulating GR expression and downregulating 11β-HSD2 expression^[4].
Jujuboside B (i.p., once every 2 days, 7 administrations, dose of 20 mg/kg) reduces the subcutaneous HCT-15 colorectal cancer tumor volume by 55.5% and tumor weight by 56.3% in female BALB/c nude mice through anti-angiogenic and anti-proliferative mechanisms, with no treatment-related body weight loss observed^[6].
When applied topically to the chick chorioallantoic membrane, Jujuboside B (1-100 μM) inhibits angiogenesis in a dose-dependent manner, with an inhibition rate of up to 80% at the concentration of 100 μM^[6].
When incorporated into subcutaneous Matrigel plugs at concentrations of 10-100 μM, Jujuboside B dose-dependently inhibits VEGF-induced angiogenesis in female BALB/c mice^[6].
Jujuboside B (i.p., once every other day, 20-40 mg/kg) dose-dependently reduces the tumor volume of A549 non-small cell lung cancer in nude mice without inducing significant hepatotoxicity or nephrotoxicity^[7].
Jujuboside B (10-100 mg/kg; p.o.; single administration) provides a statistically significant 63% protective effect against acute pulmonary thromboembolism induced by collagen and epinephrine in male ICR mice^[8].
Jujuboside B (10-50 mg/kg; i.p.; single administration 1 hour prior to hyperthermia induction) dose-dependently inhibits the severity of febrile seizures in male P14 C57BL/6 mice^[9].
Jujuboside B (40 mg/kg/day; i.p.; daily; for 2 consecutive weeks) significantly inhibits lung cancer progression in non-stressed and CUMS-stressed tumor-bearing female C57BL/6 mice by regulating apoptosis-related proteins, blocking the PI3K/Akt and MAPK/ERK signaling pathways, and reducing the levels of inflammatory cytokines^[10].
Jujuboside B (40 mg/kg; i.p.; daily for 2 consecutive weeks) significantly ameliorates depression-like behaviors in female C57BL/6 mice subjected to CUMS modeling by increasing serum 5-HT and tryptophan levels, improving behavioral scores, and reducing inflammatory cytokine levels^[10].