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Simvastatin pretreatment maintains the expression of KLF2 and its protective target genes (eNOS and TM). Westernblot analysis of KLF2, phosphorylation eNOS and total eNOS in liver tissue. β-actin is normalized as the loading control.
C4-2R cells are treated with Simvastatin, MDV3100 or combination of the two drugs at the indicated concentrations for 48 hours, followed by Immunoblotting (IB) against cleaved PARP.
Simvastatin is an inactive drug precursor that has no drug activity itself and must be metabolized into its hydroxy acid form in the liver to function. In vitro experiments, it can be activated by sodium hydroxide (NaOH).
Simvastatin suppresses cholesterol synthesis in mouse L-M cell, rat H4II E cell, and human Hep G2 cell with IC50s of 19.3 nM, 13.3 nM and 15.6 nM, respectively[1].
Simvastatin causes a dose-dependent increase in serine 473 phosphorylation of Akt within 30 minutes, with maximal phosphorylation occurring at 1.0 µM[2].
Simvastatin (1.0 μM) enhances phosphorylation of the endogenous Akt substrate endothelial nitric oxide synthase (eNOS), inhibits serum-free media undergo apoptosis and accelerates vascular structure formation[2].
Simvastatin shows anti-inflammatory effects, reduces anti-CD3/anti-CD28 antibody-stimulated proliferation of PB-derived mononuclear cells and synovial fluid cells from rheumatoid arthritis blood, as well as IFN-γ release at 10 μM[3].
Simvastatin (10 μM) also blocks cell-mediated macrophage TNF-γ release induced via cognate interactions by appr 30%[3].
Simvastatin (5 μM) significantly reduces the expression of ABCA1 in astrocytes and neuroblastoma cells, the expression of apolipoprotein E in astrocytes, and increases cyclin-dependent kinase 5 and glycogen synthase kinase 3β expression in SK-N-SH cells[7].
Simvastatin has the ability to inhibit exosome release[10].
Simvastatin (32 and 64 μM; 24, 48, and 72 h) inhibits tumor cell growth, arrests in the G0/G1 phase[11].
Simvastatin (32 and 64 μM; 48 h) induces apoptosis in HepG2 and Huh7 cells[11].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Increased early apoptosis from 9.2% in non-treated ctrl cells to 18.2% (32 μM) and 19.8% (64 μM), respectively, increased late apoptosis from 35.0% in ctrl cells to 56.9% (32 μM) and 48.0% (64 μM), respectively, in HepG2 cells.
Exhibited downregulation of CDK1, CDK2, CDK4 and cyclins D1 and E as compared to ctrl tumor cells.
In Vivo
Simvastatin suppresses the conversion of radiolabeled acetate to cholesterol with an IC50 of 0.2 mg/kg via p.o. administration[1].
Simvastatin (4 mg/day, p.o. for 13 weeks) returns the cholesterol-induced increases in total cholesterol, LDL-cholesterol and HDL-cholesterol to normal level in rabbits fed an atherogenci cholesterol-rich diet[4].
Simvastatin (6 mg/kg) increases LDL receptor-dependent binding and the number of hepatic LDL receptors in rabbits fed a diet containing 0.25% cholesterol[5].
Simvastatin (20 mg/kg/day) causes a 1.3-fold less macrophage content in lesions, and 2-fold less vascular cell adhesion molecule-1, interleukin-1beta, and tissue factor expression, companied by a 2.1-fold increases in lesional smooth muscle cell and collagen content in cynomolgus monkeys fed an atherogenic diet[6].
Simvastatin (oral gavage; 15 and 30 mg/kg; once daily; 14 d) treatment attenuats oxidative damage, TNF-a and IL-6 levels, and restores itochondrial enzyme complex activities[12].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Male wistar rats with oxidative damage by Intrastriatal 6-OHDA administration[12]
Dosage:
15 and 30 mg/kg
Administration:
Oral gavage; 15 and 30 mg/kg; once daily; 14 days
Result:
Attenuated oxidative damage (reduced MDA, nitrite levels and restoration of reduced GSH) , attenuated TNF-a and IL-6 levels, and restored itochondrial enzyme complex activities as compared to 6-OHDA group.
Room temperature in continental US; may vary elsewhere.
Storage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
1 year
-20°C
6 months
Solvent & Solubility
In Vitro:
Ethanol : 100 mg/mL (238.91 mM; Need ultrasonic)
DMSO : ≥ 50 mg/mL (119.45 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
*"≥" means soluble, but saturation unknown.
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.3891 mL
11.9454 mL
23.8909 mL
5 mM
0.4778 mL
2.3891 mL
4.7782 mL
10 mM
0.2389 mL
1.1945 mL
2.3891 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (5.97 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3
Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.97 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
Protocol 4
Add each solvent one by one: 10% EtOH 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.97 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 5
Add each solvent one by one: 10% EtOH 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.97 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
For the following dissolution methods, please prepare the working solution directly.
It is recommended to prepare fresh solutions and use them promptly within a short period of time. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution.
If precipitation or phase separation occurs during preparation,
heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 50% PEG300 50% Saline
Solubility: 10 mg/mL (23.89 mM); Suspended solution; Need ultrasonic
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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