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Kukoamine A, a spermine alkaloid, is an orally active and brain-penetrant component found in the root barks of Lycium chinense (L. chinense) Miller. Kukoamine A inhibits purified Crithidia fasciculata trypanothione reductase and soybean lipoxygenase, activates μ-opioid receptor. Kukoamine A can inhibt cancer cell proliferation, migration and invasion, cause G0/G1 phase cell cycle arrest and induce apoptosis. Kukoamine A exerts neuroprotective effect and can induce autophagy . Kukoamine A inhibits LPS (HY-D1056)-induced NO, ROS, PGE2, TNF-α, IL-1β, IL-6 production and COX-2 activity. Kukoamine A reverses palmitic acid-induced insulin resistance, lipid accumulation, and oxidative stress via downregulation of Srebp-1c. Kukoamine A can be used for the research of cancer, infection, inflammation, metabolic and neurological disease, such as glioblastoma and Parkinson's disease.
For research use only. We do not sell to patients.
Kukoamine A, a spermine alkaloid, is an orally active and brain-penetrant component found in the root barks of Lycium chinense (L. chinense) Miller. Kukoamine A inhibits purified Crithidia fasciculata trypanothione reductase and soybean lipoxygenase, activates μ-opioid receptor. Kukoamine A can inhibt cancer cell proliferation, migration and invasion, cause G0/G1 phase cell cycle arrest and induce apoptosis. Kukoamine A exerts neuroprotective effect and can induce autophagy . Kukoamine A inhibits LPS (HY-D1056)-induced NO, ROS, PGE2, TNF-α, IL-1β, IL-6 production and COX-2 activity. Kukoamine A reverses palmitic acid-induced insulin resistance, lipid accumulation, and oxidative stress via downregulation of Srebp-1c. Kukoamine A can be used for the research of cancer, infection, inflammation, metabolic and neurological disease, such as glioblastoma and Parkinson's disease[1][2][3][4][5][6][7].
Kukoamine A (1-10 μM; ~0.5-2.0 times its estimated Ki) potently inhibits purified Crithidia fasciculata trypanothione reductase as a mixed inhibitor with a Ki of 1.8 μM and Kii of 13 μM for enzyme-substrate complex, while displaying no significant inhibition of human glutathione reductase[1]. Kukoamine A (0.1 mM; 20-60 min) shows high DPPH free radical scavenging activity, with 96% reducing activity at 0.1 mM after 20 min and 60 min incubation in a cell-free system[2]. Kukoamine A potently inhibits cell-free soybean lipoxygenase, with an IC50 of 9.5 μM[2]. Kukoamine A (0.1 mM) inhibits AAPH-induced linoleic acid lipid peroxidation by 72% at 0.1 mM[2]. Kukoamine A reverses palmitic acid-induced insulin resistance, lipid accumulation, and oxidative stress in AML-12 cells via downregulation of Srebp-1c, as these protective effects are abrogated by Srebp-1c overexpression[3]. Kukoamine A (10-80 μg/mL; 1-5 days) selectively inhibits the viability of human glioblastoma U251 and WJ1 cells in a time- and dose-dependent manner, with IC50 values of 73.4 μg/mL and 22.1 μg/mL respectively at day 5, and has minimal effect on human normal liver LO2 cells and rat glioma C6 cells[4]. Kukoamine A (5-20 μg/mL; 12 days) inhibits the clonogenicity of human glioblastoma U251 and WJ1 cells in a dose-dependent manner[4]. Kukoamine A (10-80 μg/mL; 48 h) induces apoptosis in human glioblastoma U251 and WJ1 cells in a dose-dependent manner, downregulating 5-LOX and antiapoptotic Bcl-2 protein expression, and upregulating proapoptotic Bax and active caspase-3 protein expression[4]. Kukoamine A (5-20 μg/ml; 48 h) induces G0/G1 phase cell cycle arrest in human glioblastoma U251 and WJ1 cells in a dose-dependent manner[4]. Kukoamine A (10-80 μg/mL；24 h) inhibits the migration and invasion of human glioblastoma U251 and WJ1 cells in a dose-dependent manner[4]. Kukoamine A (10-40 μM; 4 h pre-incubation, followed by 24 h co-incubation with MPP+) dose-dependently protects SH-SY5Y cells from MPP+-induced injury, inhibits apoptosis and preserves mitochondrial membrane potential[5]. Kukoamine A (10-40 μM; 4 h pre-incubation, followed by 24 h co-incubation with MPP+) dose-dependently reduces Bax/Bcl-2 ratio, p-JNK and p-p38 levles and increases p-AKT, p-ERK levels in SH-SY5Y cells[5]. Kukoamine A (10-40 μM; 4 h) dose-dependently induces autophagy in SH-SY5Y cells, inducing visible autophagosomes at the highest concentration, increasing the LC3-II/LC3-I ratio, Beclin-1 and decreasing p62[5]. Kukoamine A binds to human μ-opioid receptors expressed in HEK293T cell membranes with high affinity, with a Ki value of 1.3 ± 0.18 μM and an EC50 value of 5.6 ± 0.65 μM[6]. Kukoamine A (5-40 μM; 24 h) does not reduce the viability of RAW 264.7 macrophage cells[7]. Kukoamine A (5-40 μM; 24 h) significantly inhibits LPS (HY-D1056)-induced NO, ROS, PGE2, TNF-α, IL-1β, and IL-6 production in RAW 264.7 macrophage cells in a concentration-dependent manner[7]. Kukoamine A (5-40 μM) significantly inhibits LPS-induced COX-2 activity in RAW 264.7 macrophage cells[7].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Induced a significant, dose-dependent increase in both early and late apoptotic cells, as well as total apoptotic cells, in both U251 and WJ1 cells compared to untreated controls.
human glioblastoma U251 cells, human glioblastoma WJ1 cells
Concentration:
5, 10, 20 μg/ml
Incubation Time:
48 h
Result:
Caused a significant, dose-dependent increase in the cell population in the G0/G1 phase in both U251 and WJ1 cells compared to untreated controls. Caused a corresponding significant, dose-dependent decrease in the cell population in the S phase in both U251 and WJ1 cells compared to untreated controls.
Caused a dose-dependent decrease in 5-LOX and Bcl-2 protein expression in U251 and WJ1 cells. Caused a dose-dependent increase in Bax and active caspase-3 protein expression in U251 and WJ1 cells. Caused a dose-dependent decrease in C/EBPβ, N-cadherin, vimentin, twist, and snail+slug protein expression in U251 and WJ1 cells. Caused a dose-dependent increase in E-cadherin protein expression in U251 and WJ1 cells.
4 h pre-incubation, followed by 24 h co-incubation with MPP⁺
Result:
Decreased the Bax/Bcl-2 ratio to 3.77 ± 0.36, 2.22 ± 0.17, and 0.68 ± 0.31 at 10, 20, and 40 μM, respectively. Increased p-AKT levels to 2.05 ± 0.07. Increased p-ERK levels to 3.31 ± 0.14. Decreased p-JNK levels to 0.57 ± 0.02. Decreased p-p38 levels to 0.21 ± 0.06 compared to MPP⁺-treated cells.
Significantly attenuated LPS-induced increases in TNF-α, IL-1β, and IL-6 levels in a concentration-dependent manner, with all tested concentrations showing statistically significant inhibition relative to LPS-only treated cells. Significantly reduced LPS-induced PGE2 levels, with all tested concentrations showing statistically significant inhibition relative to LPS-only treated cells. Markedly inhibited LPS-induced COX-2 activity.
In Vivo
Kukoamine A (0.01 mmol/kg; i.p.; single dose) inhibits Carrageenan (HY-125474)-induced rat paw edema by 43%[2]. Kukoamine A (5-20 mg/kg; i.p.; daily; 4 weeks) dose-dependently attenuates high fat diet-induced insulin resistance, fatty liver, inflammation, and oxidative stress in mice by inhibiting Srebp-1c and its downstream target gene expression[3]. Kukoamine A (10-40 mg/kg; i.p.; 5 times weekly; 4 weeks) inhibits in vivo glioblastoma growth in a dose-dependent manner, achieving up to 55.3% tumor inhibition at 40 mg/kg, while maintaining mouse body weight, via apoptosis induction and epithelial-mesenchymal transition attenuation mediated by downregulating 5-LOX and C/EBPβ expression[4]. Kukoamine A (5-20 mg/kg; i.g.; daily; 12 days) exerts dose-dependent neuroprotective effects in MPTP (HY-W114750)-induced Parkinson's disease mice by improving motor function, reducing neuronal apoptosis, lowering α-synuclein levels, preserving dopaminergic neurons, and enhancing autophagy, without affecting MAO-B activity[5]. Kukoamine A (5-20 mg/kg; i.g.; daily; 12 days) enhances autophagy in the SN and Str of healthy mice by regulating autophagy-related proteins, without inducing apoptosis or altering MAO-B activity[5]. Kukoamine A (25-50 mg/kg; p.o.; daily; 5 days) exerts Concentration-dependent anti-inflammatory and antioxidant effects in rats with carrageenan-induced acute inflammation, reducing paw edema, proinflammatory cytokine levels, and oxidative stress markers while enhancing liver antioxidant enzyme activity[7].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Carrageenan-induced edema Fischer-344 rats (male and female, 150-200 g, non-pregnant females; 6-15 animals per group)[2]
Dosage:
0.01 mmol/kg
Administration:
I.p.; single dose
Result:
Inhibited carrageenan-induced rat paw edema by 43%.
Animal Model:
C57 (6-8 weeks old; high fat diet-induced model)[3]
Dosage:
5 mg/kg; 10 mg/kg; 20 mg/kg
Administration:
I.p.; daily; 4 weeks
Result:
Dose-dependently inhibited HFD-induced increases in fasting blood glucose and insulin levels, and dose-dependently reduced glucose levels in response to glucose and insulin loads during IPGTT and IPITT. Dose-dependently decreased HFD-induced liver histological injury, hepatic triglyceride levels, and serum AST and ALT activities. Dose-dependently inhibited HFD-induced increases in serum TNFα, IL-1β, IL-6, and C reactive protein levels. Dose-dependently reversed HFD-induced reductions in hepatic MnSOD and CuZnSOD activities, and dose-dependently inhibited HFD-induced increases in hepatic MDA and H2O2 levels. Dose-dependently inhibited HFD-induced upregulation of hepatic Srebp-1c protein and mRNA expression, as well as hepatic mRNA expression of the Srebp-1c target genes FAS and ACC1.
Animal Model:
BALB/C-nu/nu nude mice (5-week-old, male, intraperitoneal inoculation of human GBM WJ1 cells)[4]
Dosage:
10 mg/kg; 20 mg/kg; 40 mg/kg
Administration:
I.p.; 5 times weekly; 4 weeks
Result:
Reduced mean tumor weight. Achieved tumor inhibitory rates of 35.2%, 48.8%, and 55.3% at 10, 20, and 40 mg/kg doses, respectively. Showed no difference in body weight increase compared to control mice. Significantly decreased 5-LOX, Bcl-2, C/EBPβ, N-cadherin, vimentin, twist, and snail+slug protein expression in tumor tissues in a dose-dependent manner. Significantly increased Bax, active caspase-3, and E-cadherin protein expression in tumor tissues in a dose-dependent manner.
Increased the time mice stayed on the rota-rod, reduced the time to climb down the pole, and increased traction test scores at all tested time points compared to MPTP-only mice. Increased the level of Nissl substance in the substantia nigra (SN), reversed the MPTP-induced increase in Bax and cytochrome c expression, reversed the decrease in Bcl-2 expression, and reduced caspase-3 activity in both SN and striatum (Str) in a dose-dependent manner. Decreased MPTP-induced α-synuclein elevation in SN and Str, attenuated MPTP-induced loss of tyrosine hydroxylase (TH)-positive cells in SN and Str, and attenuated MPTP-induced reduction in TH protein levels in SN and Str. Upregulated the LC3-II/LC3-I ratio and Beclin-1 expression, and downregulated p62 expression in both SN and Str.\nDid not alter MAO-B activity in the brain.
Room temperature in continental US; may vary elsewhere.
Storage
Powder
-20°C
3 years
In solvent
-80°C
6 months
-20°C
1 month
Solvent & Solubility
In Vitro:
H2O : 125 mg/mL (235.56 mM; Need ultrasonic)
DMSO : 100 mg/mL (188.44 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
1.8844 mL
9.4222 mL
18.8445 mL
5 mM
0.3769 mL
1.8844 mL
3.7689 mL
10 mM
0.1884 mL
0.9422 mL
1.8844 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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
*
Note: If you choose water as the stock solution, please dilute it to the working solution,
then filter and sterilize it with a 0.22 μm filter before use.
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 (4.71 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 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 (4.71 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.
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: PBS
Solubility: 100 mg/mL (188.44 mM); Clear 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.
Calculation results:
Working solution concentration:
mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
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).
*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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO / H2O
1 mM
1.8844 mL
9.4222 mL
18.8445 mL
47.1111 mL
5 mM
0.3769 mL
1.8844 mL
3.7689 mL
9.4222 mL
10 mM
0.1884 mL
0.9422 mL
1.8844 mL
4.7111 mL
15 mM
0.1256 mL
0.6281 mL
1.2563 mL
3.1407 mL
20 mM
0.0942 mL
0.4711 mL
0.9422 mL
2.3556 mL
25 mM
0.0754 mL
0.3769 mL
0.7538 mL
1.8844 mL
30 mM
0.0628 mL
0.3141 mL
0.6281 mL
1.5704 mL
40 mM
0.0471 mL
0.2356 mL
0.4711 mL
1.1778 mL
50 mM
0.0377 mL
0.1884 mL
0.3769 mL
0.9422 mL
60 mM
0.0314 mL
0.1570 mL
0.3141 mL
0.7852 mL
80 mM
0.0236 mL
0.1178 mL
0.2356 mL
0.5889 mL
100 mM
0.0188 mL
0.0942 mL
0.1884 mL
0.4711 mL
*
Note: If you choose water as the stock solution, please dilute it to the working solution,
then filter and sterilize it with a 0.22 μm filter before use.
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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