Viridicatol

Viridicatol is a quinolone alkaloid with anti-inflammatory, antibacterial, antifungal, osteogenic and chondrogenic activities. Viridicatol reduces the phosphorylation levels of ERK, JNK, p38 and STAT6; inhibits MMP-2, MMP-9, NF-κB signaling pathway and PTP1B; downregulates genes related to mast cell activation; and binds to SHN3 to activate the Wnt/SHN3 signaling pathway. Viridicatol inhibits the expression of pro-inflammatory mediators and cytokines, and promotes osteogenic/chondrogenic differentiation. Viridicatol can be used in studies related to fibrosarcoma, allergy, bacterial infection, fungal infection and osteoporosis^{[1][2][3][4][5]}. In Vitro:Viridicatol (10-100 μM; 24 h) exhibits no cytotoxicity toward HT1080 human fibrosarcoma cells at 10, 20, and 50 μM, but induces cytotoxicity at 100 μM^[1].
Viridicatol (10-50 μM; 1 h pre-incubation, followed by 24 h PMA stimulation) inhibits PMA-induced MMP-2 and MMP-9 enzymatic activity in HT1080 human fibrosarcoma cells^[1].
Viridicatol (10-50 μM; 1 h pre-incubation, followed by 24 h PMA stimulation) reduces PMA-induced MMP-2 protein expression in HT1080 human fibrosarcoma cells, but does not affect MMP-9 protein expression^[1].
Viridicatol (10-50 μM; 1 h pre-incubation, followed by 24 h PMA stimulation) inhibits PMA-induced phosphorylation of ERK, JNK, and p38 in HT1080 human fibrosarcoma cells^[1].
Viridicatol (10 μg/mL; 1 h pre-incubation prior to 1 h DNP-BSA stimulation) regulates 128 differentially expressed genes in IgE-mediated activated RBL-2H3 cells, primarily down-regulating mast cell activation-related inflammatory factor and chemokine genes^[2].
Viridicatol (10 μg/mL; 1 h pre-incubation prior to 1 h DNP-BSA stimulation) significantly down-regulates the expression of mast cell activation-related genes (Tnfα, Ccl2, Jun, Fos, Il4, Ccl7, Il13, and Socs1) in IgE-mediated activated RBL-2H3 cells^[2].
Viridicatol (2.5-10 μg/mL; 1 h pre-incubation prior to 15 min DNP-BSA stimulation) dose-dependently inhibits the phosphorylation of JNK, ERK, P38, and STAT6 proteins in IgE-mediated activated RBL-2H3 cells, suppressing MAPK and JAK-STAT pathway activation^[2].
Viridicatol (compound 2) (0.98-500 μg/mL; 1 day) exhibits potent antibacterial activity against Staphylococcus aureus (MIC = 15.6 μg/mL) and moderate activity against Escherichia coli, Pseudomonas aeruginosa, Streptococcus lactis, Colletotrichum gloeosporioides, and Fusarium graminearum.^[3].
Viridicatol (0.98-500 μg/mL; 2 days) exhibits potent antifungal activity against Alternaria brassicae, Botrytis cinerea, and Valsa mali (MIC = 31.2 μg/mL) and moderate activity against Alternaria alternata, Setosphearia turcica, Sclerotinia sclerotiorum, Phytophthora capsici, and Peony anthracnose^[3].
Viridicatol (compound 1) (5-160 μM; 24 h) is non-cytotoxic to RAW264.7 and BV2 cells^[4].
Viridicatol (10-80 μM; 3 h pre-treatment, followed by 24 h LPS stimulation) dose-dependently inhibits pro-inflammatory mediator production and related protein expression in LPS-stimulated RAW264.7 cells, with IC₅₀ values of 46.03 μM for NO and 30.37 μM for PGE₂^[4].
Viridicatol (10-80 μM; 3 h pre-treatment, followed by 24 h LPS stimulation) dose-dependently inhibits pro-inflammatory mediator production and related protein expression in LPS-stimulated BV2 cells, with IC₅₀ values of 43.03 μM for NO and 34.20 μM for PGE₂^[4].
Viridicatol (10-80 μM; 3 h pre-treatment, followed by 6 h LPS stimulation) differentially inhibits inflammatory gene expression in LPS‑activated RAW264.7 and BV2 cells^[4].
Viridicatol (10-80 μM; 3 h pre-treatment, followed by 1 h LPS stimulation) inhibits the NF-κB signaling pathway in LPS-stimulated RAW264.7 cells and BV2 cells by blocking IκB-α phosphorylation/degradation, NF-κB p65/p50 nuclear translocation, and NF-κB DNA-binding activity^[4].
Viridicatol (1-10 μM; 5 days) promotes early osteogenic differentiation of MC3T3-E1 pre-osteoblasts, as evidenced by concentration-dependent increases in alkaline phosphatase activity after 5 days of treatment^[5].
Viridicatol (1-20 μM; 21 days) promotes late osteogenic mineralization of MC3T3-E1 pre-osteoblasts with an EC₅₀ of 5.204 μM after 21 days of treatment^[5].
Viridicatol (1-20 μM; 14 days) promotes osteogenic mineralization of mouse bone-derived mesenchymal stem cells with an EC₅₀ of 4.132 μM after 14 days of treatment^[5].
Viridicatol (1-10 μM; ~21 days) promotes chondrogenic differentiation of mouse bone-derived mesenchymal stem cells in a concentration-dependent manner after ~21 days of treatment^[5].
Viridicatol (5 μM; 0-48 h, 3 days, 5 days, 8 days) time-dependently inhibits Hivep3 mRNA expression and upregulates osteogenic marker genes Alpl and Bglap in MC3T3-E1 pre-osteoblasts^[5].
Viridicatol (5 μM; 8 days) promotes osteogenic mineralization of WT mouse bone-derived mesenchymal stem cells, but this effect is dependent on the presence of SHN3^[5].
Viridicatol (1-10 μM; 5 days) activates the Wnt/SHN3 signaling pathway in MC3T3-E1 pre-osteoblasts by upregulating β-catenin, p-GSK-3β, and p-ERK1/2 and inhibiting SHN3 protein expression^[5].
Viridicatol (1-10 μM; 5 days, 5 μM; 3, 5, 8 days) upregulates osteocalcin and β-catenin protein levels in mouse bone-derived mesenchymal stem cells^[5]. In Vivo:Viridicatol (5 mg/kg; i.v.; daily; 6 weeks) stimulates bone formation by enhancing osteoblast activity, increasing BV/TV and trabecular bone number to prevent bone loss in ovariectomized mice^[5].
Viridicatol (5 mg/kg; i.v.; every 2 days; 14 days) promotes fracture healing by increasing callus volume, bone mass, and cartilage and bone areas at the fracture site^[5].
Free viridicatol (5 mg/kg; i.v.; every 2 days; 4 weeks) provides limited mitigation of bone loss in the Col1a2^oim/oim osteogenesis imperfecta mouse model^[5].
Viridicatol delivered via bone-targeting nanovesicles (5 mg/kg; i.v.; every 2 days; 4 weeks) significantly reduces spontaneous fractures and increases bone volume fraction in the Col1a2^oim/oim osteogenesis imperfecta mouse model^[5].