Liguzinediol
Liguzinediol is a Bcl-2 upregulator that exerts cardioprotective effects by upregulating Bcl-2, downregulating Bax and cleaved caspase-3, and inhibiting myocardial apoptosis, RAAS, oxidative stress, inflammation, and extracellular matrix remodeling. Liguzinediol can be used for research on heart failure and cardiac fibrosis.
For research use only. We do not sell to patients.
- CAS No.: 909708-65-2
- Formula: C8H12N2O2
- Molecular Weight:168.20
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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Biological Activity
Description
IC50 & Target
[1]|
Bax |
Bcl-2 |
Caspase-3 |
In Vitro
Liguzinediol (10 μM) inhibits Ang II-stimulated cardiac fibroblast proliferation, ameliorates Ang II-stimulated morphological changes in cardiac fibroblasts, and reduces the ratio of type I/III collagen in Ang II-stimulated cardiac fibroblasts[2].
Liguzinediol (10 μM) downregulates MMP-2 and MMP-9 expression and upregulates TIMP-1 expression in Ang II-stimulated cardiac fibroblasts[2].
Liguzinediol (1-100 μM) produces a positive inotropic effect in isolated rat hearts without causing chronotropic changes[5].
Liguzinediol (100 μM) has no effect on the action potential duration of rat papillary muscle and left ventricular myocytes[5].
The positive inotropic effect of Liguzinediol (100 μM) is not mediated by β-AR, PDE, Na+-K+ ATPase, α1-AR, dopamine D1 receptor, or Na+-Ca2+ exchanger in isolated rat hearts[5].
Liguzinediol (100 μM) increases Ca2+ transients in rat left ventricular cardiomyocytes and restores caffeine-induced SR Ca2+ depletion[5].
Liguzinediol (100 μM) does not increase L-type Ca2+ channel current in rat left ventricular myocytes[5].
The positive inotropic effect of Liguzinediol (100 μM) is mediated by ryanodine receptor-dependent Ca2+ release in isolated rat hearts[5].
The positive inotropic effect of liguzinediol (100 μM) is mediated through SERCA2a-dependent Ca2+ handling in isolated rat hearts[5].
Liguzinediol (100 μM; 30 min) inhibits the activities of PP1 and PP2A in rat left ventricular tissue extracts, reducing PP1 activity to 86.0% of the control level and PP2A activity to 88.8% of the control level[6].
Liguzinediol (1-100 μM; 30 min) increases phosphorylation at PLB Ser-16 and Thr-17 sites in isolated rat ventricular myocytes in a concentration-dependent manner, reaching maximum ratios of 0.85 (p-PLB Ser-16/total PLB) and 0.35 (p-PLB Thr-17/total PLB) at 100 μM, respectively[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:rat ventricular myocytes
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Concentration:1, 10, 100 μM
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Incubation Time:30 min
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Result:Increased phosphorylation at PLB Ser-16 and Thr-17 sites in isolated rat ventricular myocytes in a concentration-dependent manner.
Parmacokinetics
In Vivo
Liguzinediol (5-20 mg/kg; i.g.; once daily; two weeks) exerts protective effects against DOX-induced cardiac fibrosis in rats by reducing hydroxyproline content, decreasing the ratio of collagen type I/III, downregulating MMP-2 and MMP-9, and upregulating TIMP-1[2].
Liguzinediol (5-20 mg/kg; p.o.; daily; 8 weeks) alleviates myocardial infarction-induced heart failure in rats, and its protective effect is associated with the regulation of the TGF-β1/Smads pathway[3].
Liguzinediol (1-100 μM; retrograde coronary perfusion) produces a dose-dependent positive inotropic effect in isolated rat hearts, increasing LVDP to 187 mm Hg at 100 μM without changing heart rate[5].
Liguzinediol (20 mg/kg; intravenous injection; single administration) significantly increases left ventricular contractility in healthy male Sprague Dawley rats[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (Male, 250 g, doxorubicin-induced cardiotoxicity)[1]
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Dosage:5, 10, 20 mg/kg/d
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Administration:p.o.; once daily; 2 weeks
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Result:Improved left ventricular systolic pressure (LVSP) to 110.47 mmHg and +LV dp/dtmax to 5693.05 mmHg/s at 10 mg/kg.
Improved LVSP to 122.80 mmHg and +LV dp/dtmax to 6502.72 mmHg/s at 20 mg/kg.
Showed -LV dp/dtmax of 4212.46 mmHg/s at 5 mg/kg.
Showed Bcl-2 protein content of 0.71, Bax protein content of 1.07, and Bax/Bcl-2 ratio of 1.52 at 10 mg/kg.
Showed pro-caspase-3 protein content of 0.94 and cleaved-caspase-3 protein content of 1.85 at 10 mg/kg.
Attenuated DOX-induced injury of cardiomyocytes, decreased the number of apoptotic bodies, and resulted in normal appearing nuclei, mitochondria with only minimal swelling, and normal appearing lamellar cristae at 10 mg/kg/d.
Weakened NF-κB staining and limited the number of myocardial fiber fractures and decreased the extent of inflammatory cell infiltration at 10 mg/kg.
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Animal Model:Sprague-Dawley rats (male, 250 ± 20 g, doxorubicin-induced cardiac fibrosis)[2]
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Dosage:5, 10, 20 mg/kg
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Administration:i.g.; once daily; two weeks
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Result:Improved myocardial fiber fracture, myocardial vacuolar degeneration, and inflammatory cell infiltration at 5 mg/kg.
Reduced breakage of myocardial fiber and vacuolar degeneration significantly at 10 mg/kg.
Showed a small amount of vacuolar degeneration at 20 mg/kg.
Led to a reduction in blue collagen fibers at 5 mg/kg.
Showed significantly less blue collagen fibers than the model group at 10 mg/kg.
Almost completely prevented the deposition of blue collagen at 20 mg/kg.
Decreased hydroxyproline content in a dose-dependent manner.
Decreased the ratio of type I/III collagen to 5.06 at 10 mg/kg.
Lowered MMP-2 protein abundance to 1.21 at 10 mg/kg.
Lowered MMP-9 protein content to 0.81 at 10 mg/kg.
Increased TIMP-1 protein content to 0.69 at 10 mg/kg.
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Animal Model:Sprague-Dawley (Male, 250-300 g, myocardial infarction-induced heart failure)[3]
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Dosage:5, 10, 20 mg/kg
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Administration:p.o.; daily; 8 weeks
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Result:Up-regulated EF and LVFS at 5, 10, 20 mg/kg.
Improved SV at 10, 20 mg/kg.
Inhibited the increase of LVEDs at 20 mg/kg.
Up-regulated LVSP, ±dp/dtmax, SBP, DBP and MAP, and down-regulated LVEDP at 5, 10, 20 mg/kg.
Reduced HMI and LVMI at 10, 20 mg/kg.
Reduced collagen deposition and myocardial fibrosis, reversed the increase of HYP, and reduced collagen I and III contents at 5, 10, 20 mg/kg.
Reduced IL-6 and TNF-α levels at 5, 10, 20 mg/kg.
Inhibited the increase of IL-1β at 10, 20 mg/kg.
Reversed the increase of MDA and increased SOD level at 5, 10, 20 mg/kg.
Reduced serum TGF-β, reversed increases of TGF-β1, p-Smad2, p-Smad3 and CD105, and promoted Smad7 expression at 5, 10, 20 mg/kg.
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Animal Model:Sprague-Dawley (SD) (male, 300-350 g)[5]
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Dosage:1 μM; 10 μM; 100 μM
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Administration:retrograde coronary perfusion
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Result:Increased LVDP from a control value of 102 mm Hg to 134 mm Hg (1 μM), 158 mm Hg (10 μM), and 187 mm Hg (100 μM) in a dose-dependent manner.
Increased +dp/dtmax from 2502 mm Hg/s (control) to 2773 mm Hg/s (1 μM), 3130 mm Hg/s (10 μM), and 3551 mm Hg/s (100 μM).
Increased −dp/dtmax from 1773 mm Hg/s (control) to 1957 mm Hg/s (1 μM), 2203 mm Hg/s (10 μM), and 2594 mm Hg/s (100 μM).
Did not alter heart rate across all doses (167 bpm, 169 bpm, and 160 bpm vs. control 163 bpm).
Upon washout, LVDP returned to 110 mm Hg, +dp/dtmax to 2683 mm Hg/s, and −dp/dtmax to 1843 mm Hg/s.
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Animal Model:Sprague-Dawley (SD) (male, 300-350 g)[5]
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Dosage:100 μM
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Administration:retrograde coronary perfusion
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Result:Nimodipine (1 μM) completely blocked the positive inotropic effect of LZDO (100 μM) on LVDP, with normalized values changing from 100% (control) to 98%.\nRuthenium red (5 μM) completely blocked the positive inotropic effect of LZDO (100 μM) on LVDP, with normalized values changing from 100% (control) to 97%.\nThapsigargin (2 μM), an irreversible SR Ca2+ ATPase inhibitor, completely blocked the positive inotropic effect of LZDO (100 μM) on LVDP, with normalized values changing from 100% (control) to 95%.\nNone of the tested antagonists or inhibitors (propranolol 1 μM, IBMX 5 μM, ouabain 1 μM, prazosin 1 μM, SCH23390 1 μM, KB-R7943 1 μM) blocked the enhancing effect of LZDO (100 μM) on LVDP in isolated rat hearts.
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Animal Model:Sprague Dawley (male, 300-350 g)[6]
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Dosage:20 mg/kg
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Administration:i.v.; single dose
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Result:Decreased end-systolic volume from 82 μL to 65 μL.
Increased end-systolic pressure from 115 mm Hg to 141 mm Hg.
Increased stroke volume from 116 μL to 136 μL.
Increased ejection fraction from 58.6% to 67.6%.
Increased cardiac output from 27066 μL/min to 31312 μL/min.
Increased peak rate of rise of left ventricular pressure (+dP/dtmax) from 7207 mm Hg/s to 10022 mm Hg/s (29.2% increase).
Increased stroke work from 10395 mm Hg/μL to 14988 mm Hg/μL.
Increased slope of end-systolic pressure-volume relationship (ESPVR) from 0.96 to 1.24 (29.2% increase).
Caused no significant changes in heart rate, end-diastolic volume, end-diastolic pressure, or slope of end-diastolic pressure-volume relationship.
Chemical Information
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CAS No. 909708-65-2
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Molecular Weight 168.20
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Formula C8H12N2O2
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SMILES
OCC1=NC(=C(N=C1C)CO)C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Liguzinediol Related Classifications
HY-121864 Related Classifications
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