Esculetin
(Synonyms: 秦皮乙素) 目录号 : GC38236A coumarin with diverse actions
Cas No.:305-01-1
Sample solution is provided at 25 µL, 10mM.
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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 LRRK2G2019S, which is linked to neurotoxicity and Parkinson’s disease, in Drosophila brain lysates and decreases cell death in LRRK2G2019S-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)
Cas No. | 305-01-1 | SDF | |
别名 | 秦皮乙素 | ||
Canonical SMILES | O=C1C=CC2=CC(O)=C(O)C=C2O1 | ||
分子式 | C9H6O4 | 分子量 | 178.14 |
溶解度 | DMSO: 250 mg/mL (1403.39 mM) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 5.6136 mL | 28.0678 mL | 56.1356 mL |
5 mM | 1.1227 mL | 5.6136 mL | 11.2271 mL |
10 mM | 0.5614 mL | 2.8068 mL | 5.6136 mL |
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Esculetin: A review of its pharmacology and pharmacokinetics
Phytother Res 2022 Jan;36(1):279-298.PMID:34808701DOI:10.1002/ptr.7311.
Esculetin is a natural dihydroxy coumarin; it is mainly extracted from twig skin and the trunk bark of the Chinese herbal medicine Fraxinus rhynchophylla Hance. Emerging evidence suggests that Esculetin has a wide range of pharmacological activities. Based on its fundamental properties, including antioxidant, antiinflammatory, antiapoptotic, anticancer, antidiabetic, neuroprotective, and cardiovascular protective activities, as well as antibacterial activity, among others, Esculetin is expected to be a therapeutic drug for specific disease indications, such as cancer, diabetes, atherosclerosis, Alzheimer's disease (AD), Parkinson's disease (PD), nonalcoholic fatty liver disease (NAFLD), and other diseases. The oral bioavailability of Esculetin was shown by studies to be low. The extensive glucuronidation was described to be the main metabolic pathway of Esculetin and C-7 phenolic hydroxyl to be its major metabolic site. With the development of scientific research technology, the pharmacological effects of Esculetin are identified and its potential for the treatment of diseases is demonstrated. The underlining mechanisms of action and biological activities as well as the pharmacokinetic data of the analyzed compound reported so far are highlighted in this review with the aim of becoming a proven, and applicable insight and reference for further studies on the utilization of Esculetin.
Pharmacological and Therapeutic Applications of Esculetin
Int J Mol Sci 2022 Oct 20;23(20):12643.PMID:36293500DOI:10.3390/ijms232012643.
Esculetin is a coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as Sonchus grandifolius, Aesculus turbinata, etc. Free radicals lead to the development of oxidative stress causing inflammation, arthritis, cancer, diabetes, fatty liver disease, etc. These further reduce the efficacy of anticancer drugs, activate inflammatory signaling pathways, degrade joints and cartilage, and disrupt the glycemic index and normal function of liver enzymes. For instance, the current treatment modalities used in arthritis such as non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatoid drugs, and lipoxygenase inhibitors present limited efficacy and adverse effects. Thus, there is a constant need to find newer and safer alternatives. Esculetin has an immense antioxidative potential thereby alleviating arthritis, diabetes, malignancies, and hepatic disorders. Structurally, Esculetin contains two hydroxyl groups, which enhance its ability to function as an antioxidant by inhibiting oxidative stress in pathological conditions. Leukotriene B4 synthesis, NF-κB and MPAK pathway activation, and inflammatory cytokine production are the main causes of bone and joint deterioration in arthritis, whereas Esculetin treatment reverses these factors and relieves the disease condition. In contrast, lipid peroxidation caused by upregulation of TGF-β-mediated expression and dysfunction of antioxidant enzymes is inhibited by Esculetin therapy, thus reducing liver fibrosis by acting on the PI3K/FoxO1 pathway. Therefore, targeting NF-κB, pro-inflammatory cytokines, TGF-β and oxidative stress may be a therapeutic strategy to alleviate arthritis and liver fibrosis.
Esculetin: A phytochemical endeavor fortifying effect against non-communicable diseases
Biomed Pharmacother 2016 Dec;84:1442-1448.PMID:27810338DOI:10.1016/j.biopha.2016.10.072.
Esculetin, a naturally occurring 6,7-dihydroxy derivative of coumarin has shown its potential role in various non-communicable diseases (NCDs) including obesity, diabetes, cardiovascular, renal failure, cancer and neurological disorders. NCDs, responsible for about 70% of the deaths occurring globally are majorly attributed to tobacco or alcohol abuse, sedentary lifestyle, and unhealthy diets. It can be managed by improving access to cost-effective treatment, care and prevention. The beneficial effects of Esculetin in NCDs have been ascribed to its antioxidant, anti-proliferative and cytoprotective potential. This review attempts to summarize the beneficial effects shown by the emerging molecule and the underlying mechanisms. This may help us in improving our understanding of the molecule and may encourage the researchers to ponder over further development of Esculetin as a potential therapeutic intervention in NCDs.
Mitochondria-targeted Esculetin mitigates atherosclerosis in the setting of aging via the modulation of SIRT1-mediated vascular cell senescence and mitochondrial function in Apoe-/- mice
Atherosclerosis 2022 Sep;356:28-40.PMID:35961209DOI:10.1016/j.atherosclerosis.2022.07.012.
Background and aims: Age is a dominant and independent risk factor for the development of atherosclerosis, a major cardiovascular disease, and if left untreated leads to myocardial infarction and death. Mitochondria-targeted anti-oxidants are evolving as a new class of compounds that can alter the pathophysiology of age-related diseases, including atherosclerosis, where mitochondrial dysfunction plays a critical role in disease progression. Methods: We recently synthesized an alkyl TPP + -tagged Esculetin (mitochondria-targeted Esculetin or Mito-Esc). Apoe-/- mice were chronically (14 months) administered with Mito-Esc to investigate its efficacy in the mitigation of atherosclerosis in the setting of aging. We monitored BP, and performed various biochemical assays, histopathology, immunohistochemistry, inflammatory factors, qPCR, and Western blotting. Simultaneously, human aortic endothelial cells (HAECs) were used as a model system to study the mechanistic aspects. Results: A chronic low-dose administration of Mito-Esc to Apoe-/- mice greatly prevented alterations in lipid profile, blood pressure, and atherosclerotic plaque formation in the setting of aging. Mito-Esc administration significantly reduced vascular senescence and pro-inflammatory cytokines levels and prevented dysregulation of mitochondrial biogenesis markers in aortic tissue. Further, Mito-Esc treatment prevented replicative and stress-induced premature senescence (SIPS) in HAEC. Importantly, Mito-Esc treatment delayed endothelial cell senescence by increasing human telomerase reverse transcriptase (hTERT) levels via SIRT1 activation. Moreover, Mito-Esc treatment by altering miR-19b and miR-30c via a SIRT1 activation significantly inhibited the increase in PAI-1 levels in HAEC as well as in the serum of Apoe-/- mice. In addition, Mito-Esc treatment improved mitochondrial function in late passage (aged) HAECs by enhancing the oxygen consumption rate (OCR). Furthermore, Mito-Esc administration counteracted the decline in GSH and nitrite levels in Apoe-/- mice and in HAECs. Conclusions: Overall, Mito-Esc alleviates atherosclerosis in the setting of aging by delaying vascular senescence and pro-inflammatory processes, and by improving mitochondrial biogenesis and function.
Pharmacological Activities and Synthesis of Esculetin and Its Derivatives: A Mini-Review
Molecules 2017 Mar 2;22(3):387.PMID:28257115DOI:10.3390/molecules22030387.
Esculetin, synonymous with 6,7-dihydroxycoumarin, is the main active ingredient of the traditional Chinese medicine Cortex Fraxini. The twig skin or trunk bark of Cortex Fraxini are used by herb doctors as a mild, bitter liver and gallbladder meridians' nontoxic drug as well as dietary supplement. Recently, with a variety of novel Esculetin derivatives being reported, the molecular mechanism research as well as clinical application of Cortex Fraxini and Esculetin are becoming more attractive. This mini-review will consolidate what is known about the biological activities, the mechanism of Esculetin and its synthetic derivatives over the past decade in addition to providing a brief synopsis of the properties of Esculetin.