Mito-Esculetin
Mito-Esculetin (Mito-Esc) is an orally active mitochondria-targeted derivative of Esculetin (HY-N0284). Mito-Esculetin inhibits LPS-induced phosphorylation of STAT3 Tyr-705, partially reverses LPS-mediated depletion of SIRT3, and enhances the AMPK-SIRT1 signaling axis. Mito-Esculetin inhibits PAI-1 activity, regulates miRNA, and induces phosphorylation of IRS and AKT. Mito-Esculetin suppresses oxidant-induced endothelial dysfunction, Ang-II (HY-13948)- and high glucose-induced atherosclerotic plaque formation, Palmitate (HY-N0830)-induced insulin resistance, as well as high glucose-mediated endothelial cell senescence and inflammatory responses. Mito-Esculetin reduces body weight and non-esterified fatty acid (NEFA) levels. Mito-Esculetin can be used in research related to acute coronary syndrome, type 2 diabetes, and hyperglycemia-induced atherosclerosis.
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- CAS No.: 1993461-76-9
- Formule: C35H36BrO4P
- Masse moléculaire:631.54
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
- Références
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Activité biologique
Description
In Vitro
Mito-Esculetin (10 μM; 10 min) inhibits the activity of recombinant PAI-1 in cell-free biochemical assays[1].
Mito-Esculetin (2.5 μM; 2 h pretreatment) significantly inhibits PAI-1 activity and mRNA expression in lipopolysaccharide (LPS)-induced human aortic endothelial cells (HAECs), and its efficacy is stronger than that of the parent compound Esculetin (HY-N0284)[1].
Mito-Esculetin (2.5 μM; 2 h) inhibits lipopolysaccharide (LPS)-induced phosphorylation of STAT3Tyr-705 in human aortic endothelial cells (HAECs)[1].
Mito-Esc (1.25 μM; 6 h) inhibits gluconeogenesis, restores the insulin signaling pathway, enhances glucose uptake, and promotes GLUT4 translocation in palmitate-induced insulin-resistant HepG2 cells[2].
Mito-Esc (1.25 μM; 1 h pre-incubation) inhibits high glucose-induced adhesion between monocytes and HAEC[2].
Mito-Esc (1.25 μM; 1 h pre-incubation) attenuates high glucose-induced senescence and oxidative stress, restores the AMPK-eNOS-SIRT1 signaling pathway in HAECs, and this effect depends on functionally intact AMPK and SIRT1[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Human aortic endothelial cells (HAECs)
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Concentration:2.5 μM
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Incubation Time:2 h pretreatment, followed by 4 h LPS co-incubation
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Result:Significantly inhibited LPS-induced PAI-1 activity in conditioned medium.
Significantly reduced LPS-induced PAI-1 transcript levels.
Exerted a more pronounced inhibitory effect than parent esculetin.
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Cell Line:Human aortic endothelial cells (HAECs)
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Concentration:2.5 μM
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Incubation Time:2 h pretreatment, followed by 4 h LPS co-incubation
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Result:Greatly inhibited LPS-induced increases in phospho-STAT3 (Tyr-705) protein levels.
In Vivo
Mito-Esculetin (0.312-1.25 mg/kg; p.o.; daily; 30 days) administered orally to db/db mice dose-dependently improves glucose homeostasis, insulin resistance, liver function, adipose tissue health, and hyperglycemia-induced atherosclerosis by reducing inflammation, senescence, and oxidative stress, with the 1.25 mg/kg dose showing the greatest efficacy[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ApoE-/- (2-month-old male, Angiotensin II-induced atherosclerosis)[1]
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Dosage:0.5 mg/kg
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Administration:p.o.; daily; 2 months
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Result:Significantly inhibited Ang-II-induced plasma PAI-1 levels.
Repressed Ang-II-mediated elevation of aortic miR-19b levels.
Restored Ang-II-reduced aortic miR-30c levels.
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Animal Model:db/db (4-month-old male/female; spontaneous hyperglycemia, insulin resistance, dyslipidemia)[2]
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Dosage:0.312 mg/kg; 0.625 mg/kg; 1.25 mg/kg
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Administration:p.o.; daily; 30 days
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Result:Significantly reduced fasting and random blood glucose levels, and HbA1c levels relative to db/db controls.
Normalized serum insulin levels, and increased the quantitative insulin sensitivity check (QUICK) index dose-dependently.
Dose-dependently improved liver tissue morphology, reduced serum AST and ALT levels, decreased liver LDL-cholesterol and triglyceride levels, increased liver glycogen content, inhibited liver fructose-1,6-bisphosphatase (FBPase) activity, and reduced liver non-esterified free fatty acid (NEFA) levels relative to db/db controls.
Dose-dependently reduced adipocyte hypertrophy and lipid accumulation in adipose tissue relative to db/db controls, with greater reduction than simvastatin and pioglitazone.
Dose-dependently reduced aortic lesion area, collagen accumulation, and lipid accumulation relative to db/db controls; 0.625 and 1.25 mg/kg doses showed greater reduction than simvastatin and pioglitazone.
Significantly reduced serum LDL-cholesterol and triglyceride levels dose-dependently, while HDL levels were unchanged.
Significantly reduced mean arterial blood pressure.
Dose-dependently reduced aortic VCAM-1, ICAM-1, and MAC3 expression, normalized M1/M2 macrophage marker transcript levels in aorta, and reduced serum TNF-α, IL-1β, IL-6, IL-10, and MCP-1 levels relative to db/db controls; the 1.25 mg/kg dose showed greater reduction in TNF-α, IL-6, and MCP-1 than simvastatin and pioglitazone.
Dose-dependently reduced aortic transcript levels of senescence markers p16, p21, p27, and p53, restored aortic phospho-AMPK, phospho-eNOS, and SIRT1 protein levels, and increased serum GSH and nitrite/nitrate levels relative to db/db controls.
Chemical Information
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CAS No. 1993461-76-9
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Masse moléculaire 631.54
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Formule C35H36BrO4P
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SMILES
O=C1OC2=C(C(CCCCCCCC[P+](C3=CC=CC=C3)(C4=CC=CC=C4)C5=CC=CC=C5)=C1)C=C(O)C(O)=C2.[Br-]
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Synonyms
Mito-Esc
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Katta S, et al. Mitochondria-targeted esculetin inhibits PAI-1 levels by modulating STAT3 activation and miR-19b via SIRT3: Role in acute coronary artery syndrome. J Cell Physiol. 2018 Jan;233(1):214-225. [Content Brief]
[2]. Singuru G, et al. Mitochondria targeted esculetin administration improves insulin resistance and hyperglycemia-induced atherosclerosis in db/db mice. J Mol Med (Berl). 2024;102(7):927-945. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Mito-Esculetin Related Classifications
HY-184265 Related Classifications
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