Wedelolactone

Wedelolactone (IKK Inhibitor II) is a natural product derived from Eclipta prostrata that inhibits NF-κB-mediated gene transcription in cells by blocking the phosphorylation and degradation of IκBα, and exhibits anticancer, anti-inflammatory, and antioxidant activities. Wedelolactone induces caspase-dependent apoptosis in prostate cancer cells by downregulating PKCε, without inhibiting Akt. Wedelolactone inhibits 5-Lox with an IC50 value of 2.5 μM. Wedelolactone can be used in research on inflammation, tumors, liver disease, and immune-related diseases.

5-LOX:2.5 μM (IC50)

Methods: RAW264.7 mouse macrophages were pretreated with wedelolactone (5, 10, 20 μM) for 1 hour, followed by stimulation with LPS (500 ng/mL) for 24 hours. TNF-α, IL-6, and NO levels were measured by ELISA.
Results: Wedelolactone dose-dependently inhibited LPS-induced cytokine release and gene expression. [1]
Methods: Wedelolactone (10 μM) was added to chondrogenically differentiated hiPSC-MSC spheroids and treated for 21 days, followed by RNA-seq analysis of gene changes.
Results: Omics data indicated that the FOXO signaling pathway was significantly activated and that wedelolactone upregulated FOXO1 mRNA and protein levels. [2]
Methods: Mouse bone marrow mesenchymal stem cells (BMSCs) were treated with wedelolactone at different concentrations (0, 0.625, 1.25, 2.5, 5 μg/mL) were applied to mouse bone marrow mesenchymal stem cells (BMSCs). ALP staining and alizarin red/von Kusserau staining were used to assess osteogenic differentiation and mineralization; qPCR was used to detect osteogenic marker genes; and Western blot and kinase assays were performed to analyze the Wnt/GSK3β/β-catenin pathway.
Results: 1.25 μg/mL Wedelolactone significantly promoted ALP activity and bone mineralization, and upregulated the expression of Osterix, Osteocalcin, and Runx2; by inhibiting GSK3β and increasing GSK3β phosphorylation levels, it promoted the nuclear translocation of β-catenin and Runx2, and activated the Wnt pathway to enhance osteogenic differentiation. [3]
Methods: RANKL-induced RAW264.7 osteoclast precursor cells were treated with different concentrations (0, 0.625, 1.25, 2.5, 5 μg/mL) of wedelolactone. Actin rings were observed using FITC-phalloidin staining, and resorption pits were detected in dentin sections. qPCR was used to detect osteoclast-related genes, and Western blot and immunofluorescence were employed to analyze the NF-κB/c-Fos/NFATc1 pathway.
Results: Wedelolactone significantly inhibited osteoclast actin ring formation and bone resorption function, downregulated the expression of c-Src, c-Fos, and cathepsin K; inhibited NF-κB p65 phosphorylation and blocked NFATc1 nuclear translocation, thereby suppressing the NF-κB/c-Fos/NFATc1 pathway to reduce osteoclastogenesis.[3]

Methods: Male C57BL/6J mice (WT) received Wedelolactone (5, 10, 20 mg/kg) via oral gavage once daily for 7 consecutive days. One hour after the final dose, LPS (5 mg/kg) was administered via tracheal instillation. Tissue samples were collected 24 hours after LPS stimulation.
Results: Wedelolactone dose-dependently reduced pulmonary tissue pathological damage, inhibited NF-κB activation in lung tissue, activated the Nrf2 pathway, and improved mitochondrial morphology and related protein expression. [1]
Methods: SD rats underwent full-thickness cartilage defect creation (diameter 1.5 mm, depth 1.5 mm) at the mid-trochanteric region of the femur. Rat BMSCs pretreated with Wedelolactone (10 μM) for 3 days were implanted with hydrogel. Specimens were collected 6 weeks post-implantation.
Results: The defect area in the Wedelolactone pretreatment group demonstrated superior cartilage repair outcomes.[2]

DMSO: 252.5 mg/mL (803.5 mM), Sonication is recommended.

Chloroform, Dichloromethane, Ethyl Acetate, Acetone, etc.: Soluble

10% DMSO+40% PEG300+5% Tween 80+45% Saline: 5.7 mg/mL (18.14 mM), Solution.