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Wedelolactone
Wedelolactone is an inhibitor of IKK.
IkB kinase (IKK) complex contains the catalytic subunits IKKα and IKKβ, and the regulatory subunit IKKγ/NEMO. IKK, is a kinase critical for activation of NF-κB by mediating phosphorylation and degradation of IκBα. The induction of caspase-11 is an important upstream controlling event in inflammatory response and apoptosis under pathological conditions modulated by upstream NF-κB-mediated transcription[1].
In vitro: In cultured mouse BALB/c 3T3 cells, mouse splenocytes and HeLa cells, wedelolactone (0~100 μM) inhibited LPS-induced caspase-11 expression by inhibiting NF-κB-mediated transcription through the direct inhibition of IKK. Wedelolactone played an potential role in anti-inflammatory therapy to inhibit IL-1β levels in diseases such as rheumatoid arthritis, asthma and septic shock[1].
In vivo: On Swiss albino male mouse skin, IKK inhibition by wedelolactone (10 μM) prevented the induction of NF-κB, perturbed the generation of reactive oxygen species and reactive nitrogen intermediates, blunted the signal transduction that lead to the activation of the early immediate genes, and thereby protected mouse skin from the UVB induced neoplastic transformation, angiotropism and metastatic progression [2].
References:
[1] Kobori M, Yang Z, Gong D, et al. Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK complex.[J]. Cell Death & Differentiation, 2004, 11(1):123-30.
[2] Ali F, Khan B A, Sultana S. Wedelolactone mitigates UVB induced oxidative stress, inflammation and early tumor promotion events in murine skin: plausible role of NFκB pathway[J]. European Journal of Pharmacology, 2016, 786:253-264.
| Storage | Store at -20°C |
| M.Wt | 314.25 |
| Cas No. | 524-12-9 |
| Formula | C16H10O7 |
| Solubility | insoluble in EtOH; insoluble in H2O; ≥44.4 mg/mL in DMSO |
| Chemical Name | 1,8,9-trihydroxy-3-methoxy-[1]benzofuro[3,2-c]chromen-6-one |
| SDF | Download SDF |
| Canonical SMILES | COC1=CC(=C2C(=C1)OC(=O)C3=C2OC4=CC(=C(C=C43)O)O)O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
Mouse BALB/c 3T3 cells, mouse splenocytes from C57/B6 mice, HeLa cells |
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Preparation method |
Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1 h, 0~100 μM |
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Applications |
In cultured mouse BALB/c 3T3 cells, mouse splenocytes and HeLa cells, wedelolactone (0~100 μM) inhibited LPS-induced caspase-11 expression by inhibiting NF-κB-mediated transcription through the direct inhibition of IKK. In BALB/c 3T3 cells and/or HeLa cells, wedelolactone inhibited the endogenous IKK activity at 50 μM, the phosphorylation as well as degradation of IκBα at 100 μM, NF-κB transcriptional activity and the LPS-induced caspase-11 mRNA expression at 60 μM. In mouse splenocytes, wedelolactone (50 μM and 100 μM) also inhibited the secretion of the proinflammatory cytokine IL-1β, which maturated by caspase-11-activated caspase-1. |
| Animal experiment [2]: | |
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Animal models |
Swiss albino male mice |
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Dosage form |
Wedelolactone 10 μM in 200 μl acetone 1 h before and after every UVB exposure (0.42 J/m2 for 6 h), three weekly for 21 days |
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Application |
On Swiss albino male mouse skin, IKK inhibition by wedelolactone (10 μM) produced profound effect on several molecular targets of UVB induced cell signaling, including GSH, GST, GPx, LPO, CAT, MPO, NO, cGMP, PKC, NF-κB, COX-2, VEGF, etc. Wedelolactone prevented the induction of NF-κB, and thereby limited inflammation and modulated cell environment to a non-persuasive state for neoplastic transformation, and also limited the reactive oxygen species generation following UVB exposure. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Kobori M, Yang Z, Gong D, et al. Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK complex.[J]. Cell Death & Differentiation, 2004, 11(1):123-30. [2] Ali F, Khan B A, Sultana S. Wedelolactone mitigates UVB induced oxidative stress, inflammation and early tumor promotion events in murine skin: plausible role of NFκB pathway[J]. European Journal of Pharmacology, 2016, 786:253-264. |
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