Esculetin

Esculetin is a coumarin that has been found in Euphorbia and has diverse biological activities.^1,2,3,4,5 It inhibits 5-lipoxygenase (5-LO) and 12-LO (IC₅₀s = 4 and 2.5 ?M, respectively), as well as the histone demethylase jumonji AT-rich interactive domain 1B (JARID1B; IC₅₀ = 4.6 ?M).^1,2 Esculetin is active against B. cereus, S. lutea, S. aureus, S. lactis, A. faecalis, and E. coli.³ It reduces production of hydrogen peroxide induced by the leucin-rich repeat kinase 2 (LRRK2) mutant LRRK2^G2019S, which is linked to neurotoxicity and Parkinson’s disease, in Drosophila brain lysates and decreases cell death in LRRK2^G2019S-expressing primary human cortical neurons.⁴ Esculetin (1.68 ?mol/ear) reduces croton oil-induced ear edema in mice.⁵ It also inhibits acetylcholine-induced writhing in mice (ED₅₀ = 69 mg/kg).

1.Neichi, T., Koshihara, Y., and Murota, S.I.Inhibitory effect of esculetin on 5-lipoxygenase and leukotriene biosynthesisBiochim. Biophys. Acta753130-132(1983) 2.Sayegh, J., Cao, J., Zou, M.R., et al.Identification of small molecule inhibitors of Jumonji AT-rich interactive domain 1B (JARID1B) histone demethylase by a sensitive high throughput screenJ. Biol. Chem.288(13)9408-9417(2013) 3.Jurd, L., Corse, J., King, A.D., Jr., et al.Antimicrobial properties of 6,7-dihydroxy-, 7,8-dihydroxy-, 6-hydroxy- and 8-hydroxycoumarinsPhytochem.10(12)2971-2974(1971) 4.Angeles, D.C., Ho, P., Dymock, B.W., et al.Antioxidants inhibit neuronal toxicity in Parkinson's disease-linked LRRK2Ann. Clin. Transl. Neurol.3(4)288-294(2016) 5.Tubaro, A., Del Negro, P., Ragazzi, E., et al.Anti-inflammatory and peripheral analgesic activity of esculetin in vivoPharmacol. Res. Commun.20(5)83-85(1988)