Kukoamine B
(Synonyms: 地骨皮乙素) 目录号 : GC44017
A dual inhibitor of LPS and CpG DNA
Cas No.:164991-67-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kukoamine B is a spermine alkaloid first isolated from a traditional Chinese herb L. chinense that inhibits both lipopolysaccharides (LPS) and oligodeoxynucleotides containing CpG motifs (CpG DNA). It is reported to inhibit proinflammatory signal transduction and cytokine expression induced by LPS and CpG DNA (Kds = 1.24 and 0.66 µM). LPS and CpG DNA are two well-recognized pathogen-associated molecular patterns (PAMPs) that play a role in triggering sepsis, thus sepsis may be attenuated by simultaneously neutralizing LPS and CpG DNA.
| Cas No. | 164991-67-7 | SDF | |
| 别名 | 地骨皮乙素 | ||
| Canonical SMILES | OC1=C(O)C=CC(CCC(N(CCCCNCCCNC(CCC2=CC(O)=C(O)C=C2)=O)CCCN)=O)=C1 | ||
| 分子式 | C28H42N4O6 | 分子量 | 530.7 |
| 溶解度 | DMF: 30 mg/mL,DMSO: 30 mg/mL,Ethanol: 30 mg/mL,PBS (pH 7.2): 10 mg/mL | 储存条件 | Store at -20°C,protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8843 mL | 9.4215 mL | 18.843 mL |
| 5 mM | 0.3769 mL | 1.8843 mL | 3.7686 mL |
| 10 mM | 0.1884 mL | 0.9422 mL | 1.8843 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Kukoamine B from Lycii Radicis Cortex Protects Human Keratinocyte HaCaT Cells through Covalent Modification by Trans-2-Nonenal
Plants (Basel) 2022 Dec 29;12(1):163.PMID:36616291DOI:10.3390/plants12010163.
The unsaturated aldehyde trans-2-nonenal is known to be generated by lipid peroxidation at the surface of the skin in an aging-related manner and has harmful effects on keratinocytes in the skin. In this study, the protective effect of a Lycii Radicis Cortex (LRC) extract against trans-2-nonenal-induced cell damage on human keratinocyte cell lines (HaCaT) was investigated. Notably, treatment with the LRC extract resulted in an increase in cell survival, while trans-2-nonenal decreased the viability of HaCaT cells. For identification of interaction between the LRC extract and trans-2-nonenal, this mixture was incubated in simulated physiological conditions, showing a strong decrease in the amount of trans-2-nonenal by the LRC extract. Subsequent LC-ESI-MS analysis revealed that Kukoamine B (KB) formed Schiff base-derived pyridinium adducts with trans-2-nonenal. Thus, these results suggest that KB could be a potential agent that may protect HaCaT cells by forming new products with trans-2-nonenal.
Fixed dosing of Kukoamine B in sepsis patients: Results from population pharmacokinetic modelling and simulation
Br J Clin Pharmacol 2022 Sep;88(9):4111-4120.PMID:35373389DOI:10.1111/bcp.15342.
Aims: To assess the appropriateness of the body weight or fixed dosing regimen, a population pharmacokinetic (PopPK) model of Kukoamine B has been built in sepsis patients. Methods: Plasma concentrations of Kukoamine B and the covariates information were taken from 30 sepsis patients assigned into 0.06 mg/kg, 0.12 mg/kg and 0.24 mg/kg groups in a Phase IIa clinical trial. The PopPK model was built using a nonlinear mixed-effect (NLME) modelling approach. Based on the final model, PK profiles were respectively simulated 500 times applying the body weight and renal function information of 12 sepsis patients from the 0.24 mg/kg group on the body weight or the fixed dosing regimen. For each dosing regimen, PK profiles of 6000 virtual patients were obtained. Statistical analyses for Cmax and Cmin were performed. If the biases of Cmax and Cmin can all meet the criteria of ±15%, the fixed dosing regimen can substitute for the body weight dosing regimen. Results: The PopPK model was successfully developed using the NLME approach. A bi-compartmental model was selected as the basic model. Renal function was identified as a statistically significant covariate of systemic clearance with the objective function value (OFV) decreasing 8.6, resulting in a 5.2% decrease in inter-individual variability (IIV) of systemic clearance. Body weight was not identified as a statistically significant covariate. Simulation results demonstrated two methods had a bias of 8.1% for Cmax , and 8.6% for Cmin . Furthermore, PK variability was lower on the fixed dosing regimen than the body weight regimen. Conclusions: Based on the simulation results, a fixed dosing regimen was recommended in the subsequent clinical trials.
Kukoamine B Ameliorate Insulin Resistance, Oxidative Stress, Inflammation and Other Metabolic Abnormalities in High-Fat/High-Fructose-Fed Rats
Diabetes Metab Syndr Obes 2020 May 26;13:1843-1853.PMID:32547146DOI:10.2147/DMSO.S247844.
Background: Obesity is characterized by excessive body fat, insulin resistance and dyslipidemia, which increases the chances of developing chronic diseases like type 2 diabetes, cardiovascular diseases, hypertension, nonalcoholic fatty liver diseases, some types of cancers and neurodegenerative diseases. Kukoamine B (Kuk B) is a spermine alkaloid obtained from Lycium chinense, and it has been shown to possess antidiabetic, antioxidant and anti-inflammatory properties. In this study, we evaluated the therapeutic effect of Kuk B on high-fat diet/high-fructose (HFDFr)-induced insulin resistance and obesity in experimental rats. Materials and methods: Rats were fed with either normal rat diet or HFDFr for 10 consecutive weeks. The groups that were fed with HFDFr received Kuk B (25 and 50 mg/kg) from the beginning of the 6th week to the 10th week. After treatment, the effect of Kuk B on body weight, food, water intake, insulin, blood glucose, serum biochemical parameters, hepatic oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and proinflammatory cytokine (interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor alpha (TNF-α)) levels was determined. Histopathological analysis of the liver tissues was also performed. Results: HFDFr-fed rats showed a significant increase in body weight, fasting blood glucose, insulin, lipid accumulation and liver function enzymes. In addition, HFDFr diet increased hepatic MDA, TNF-α, IL-1β and IL-6 and decreased hepatic SOD, CAT and GSH-Px activities. On the other hand, Kuk B significantly attenuated body weight, insulin resistance, lipid accumulation, oxidative stress and inflammation. Conclusion: These results indicated that Kuk B showed protective effect against HFDFr-induced metabolic disorders by downregulating lipid accumulation, oxidative stress and inflammatory factors.
Kukoamine B promotes TLR4-independent lipopolysaccharide uptake in murine hepatocytes
Oncotarget 2016 Sep 6;7(36):57498-57513.PMID:27542278DOI:10.18632/oncotarget.11292.
Free bacterial lipopolysaccharide (LPS) is generally removed from the bloodstream through hepatic uptake via TLR4, the LPS pattern recognition receptor, but mechanisms for internalization and clearance of conjugated LPS are less clear. Kukoamine B (KB) is a novel cationic alkaloid that interferes with LPS binding to TLR4. In this study, KB accelerated blood clearance of LPS. KB also enhanced LPS distribution in the hepatic tissues of C57 BL/6 mice, along with LPS uptake in primary hepatocytes and HepG2 cells. By contrast, KB inhibited LPS internalization in Kupffer and RAW 264.7 cells. Loss of TLR4 did not affect LPS uptake into KB-treated hepatocytes. We also detected selective upregulation of the asialoglycoprotein receptor (ASGPR) upon KB treatment, and ASGPR colocalized with KB in cultured hepatocytes. Molecular docking showed that KB bound to ASGPR in a manner similar to GalNAc, a known ASGPR agonist. GalNAc dose-dependently reduced KB internalization, suggesting it competes with KB for ASGPR binding, and ASGPR knockdown also impaired LPS uptake into hepatocytes. Finally, while KB enhanced LPS uptake, it was protective against LPS-induced inflammation and hepatocyte injury. Our study provides a new mechanism for conjugated LPS hepatic uptake induced by the LPS neutralizer KB and mediated by membrane ASGPR binding.
Antioxidant and Cytoprotective Effects of Kukoamines A and B: Comparison and Positional Isomeric Effect
Molecules 2018 Apr 21;23(4):973.PMID:29690528DOI:10.3390/molecules23040973.
In this study, two natural phenolic polyamines, kukoamine A and B, were comparatively investigated for their antioxidant and cytoprotective effects in Fenton-damaged bone marrow-derived mesenchymal stem cells (bmMSCs). When compared with Kukoamine B, kukoamine A consistently demonstrated higher IC50 values in PTIO•-scavenging (pH 7.4), Cu2+-reducing, DPPH•-scavenging, •O₂−-scavenging, and •OH-scavenging assays. However, in the PTIO•-scavenging assay, the IC50 values of each kukoamine varied with pH value. In the Fe2+-chelating assay, Kukoamine B presented greater UV-Vis absorption and darker color than kukoamine A. In the HPLC⁻ESI⁻MS/MS analysis, kukoamine A with DPPH• produced radical-adduct-formation (RAF) peaks (m/z 922 and 713). The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay suggested that both kukoamines concentration-dependently increased the viabilities of Fenton-damaged bmMSCs at 56.5⁻188.4 μM. However, kukoamine A showed lower viability percentages than Kukoamine B. In conclusion, the two isomers kukoamine A and B can protect bmMSCs from Fenton-induced damage, possibly through direct or indirect antioxidant pathways, including electron-transfer, proton-transfer, hydrogen atom transfer, RAF, and Fe2+-chelating. Since Kukoamine B possesses higher potentials than kukoamine A in these pathways, Kukoamine B is thus superior to kukoamine A in terms of cytoprotection. These differences can ultimately be attributed to positional isomeric effects.