L-Norvaline
(Synonyms: L-正缬氨酸) 目录号 : GC60999
An inhibitor of arginase and p70S6K1
Cas No.:6600-40-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
L-Norvaline is a non-proteinogenic amino acid, an isomer of valine, and an inhibitor of arginase and p70 ribosomal S6 kinase 1 (p70S6K1) kinase.1,2 It inhibits arginase-mediated urea production in J774A.1 macrophage lysates when used at a concentration of 10 mM and TNF-α-induced p70S6K1 activation in human umbilical vein endothelial cells (HUVECs) at 20 mM.1 L-Norvaline reduces microgliosis and the level of amyloid-β fibrils in the hippocampus, as well as improves learning and memory in the Morris water maze in the 3xTg mouse model of Alzheimer’s disease.3
1.Chang, C.-I., Liao, J.C., and Kuo, L.Arginase modulates nitric oxide production in activated macrophagesAm. J. Physiol.274(1)H342-H348(1998) 2.Ming, X.-F., Rajapakse, A.G., Carvas, J.M., et al.Inhibition of S6K1 accounts partially for the anti-inflammatory effects of the arginase inhibitor L-norvalineBMC Cardiovasc. Disord.912(2009) 3.Polis, B., Srikanth, K.D., Elliott, E., et al.L-Norvaline reverses cognitive decline and synaptic loss in a murine model of Alzheimer's diseaseNeurotherapeutics15(4)1036-1054(2018)
| Cas No. | 6600-40-4 | SDF | |
| 别名 | L-正缬氨酸 | ||
| Canonical SMILES | N[C@@H](CCC)C(O)=O | ||
| 分子式 | C5H11NO2 | 分子量 | 117.15 |
| 溶解度 | 储存条件 | Store at -20°C | |
| 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 | 8.5361 mL | 42.6803 mL | 85.3606 mL |
| 5 mM | 1.7072 mL | 8.5361 mL | 17.0721 mL |
| 10 mM | 0.8536 mL | 4.268 mL | 8.5361 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。
Antihyperglycemic activity of L-Norvaline and L-arginine in high-fat diet and streptozotocin-treated male rats
Exp Mol Pathol 2022 Jun;126:104763.PMID:35398371DOI:10.1016/j.yexmp.2022.104763.
Background: A decrease in nitric oxide (NO) bioavailability has been shown to cause hyperglycemia, type II diabetes mellitus (DM), and chronic cardio-metabolic complications. In turn, hyperglycemia and hypercholesterolemia are associated with increased oxidative stress that leads to reduced nitric oxide bioavailability through disruption of L-arginine transport into cells, inactivation of nitric oxide synthase, and activation of arginase. Upregulation of arginase has been demonstrated in both diabetic patients and animal models of hyperglycemia and type 2 diabetes. L-Norvaline is a nonselective inhibitor of arginase that increases NO production and promotes the normal functioning of the vascular endothelium. Another means of increasing NO bioavailability in the cardiovascular system is L-arginine supplementation. Whether L-Norvaline and L-arginine have antihyperglycemic effects has not been studied. Hypothesis: We hypothesized that inhibition of arginase will provide an antihyperglycemic effect and, as a result of the recovery of NO bioavailability, will protect against oxidative stress and hypercholesterolemia. Methods: Rats were fed a high-fat diet (HFD) for three weeks concomitant with the two-time injection of 30 mg/kg of streptozotocin (STZ) to induce stable hyperglycemia. We studied the antihyperglycemic properties of arginase inhibition (via L-Norvaline) and its combination with NOS substrate supplementation (via L-arginine). Results: Treatment of HFD/STZ mice with L-Norvaline and L-arginine reduced fasting blood glucose levels by 27.1% vs. untreated HFD/STZ rats (p < 0.001). Blood levels of total cholesterol, low-density lipoprotein (LDL), and malondialdehyde (MDA), a marker for oxidative stress, were significantly decreased in both L-norvaline- and L-Norvaline+L-arginine-treated HFD/STZ rats when compared with untreated rats. In addition, administration of L-Norvaline and L-arginine reversed the progression of pancreatic and kidney pathology in HFD/STZ rats as assessed by histology (p < 0.001). Conclusions: Both L-Norvaline and L-arginine act as potent antihyperglycemic agents and can represent alternative therapeutic tools in individuals with hyperglycemia and pre-diabetes.
L-Norvaline affects the proliferation of breast cancer cells based on the microbiome and metabolome analysis
J Appl Microbiol 2022 Aug;133(2):1014-1026.PMID:35543360DOI:10.1111/jam.15620.
Aims: The altered faecal metabolites and microbiota might be involved in the development of breast cancer. We aimed to investigate the effect of differential metabolites on the proliferative activity of breast cancer cells. Methods and results: We collected faecal samples from 14 breast cancer patients and 14 healthy subjects. Untargeted metabolomics analysis, short-chain fatty acid (SCFA) targeted analysis, and 16S rDNA sequencing was performed. The gut metabolite composition of patients changed significantly. Levels of norvaline, glucuronate and galacturonate were lower in the cancer group than in the Control (p < 0.05). 4-Methylcatechol and guaiacol increased (p < 0.05). Acetic acid and butyric acid were lower in the cancer group than in the control group (p < 0.05). Isobutyric acid and pentanoic acid were higher in the cancer group than in the control (p < 0.05). In the genus, the abundance of Rothia and Actinomyces increased in the cancer group, compared with the control group (p < 0.05). The differential microbiotas were clearly associated with differential metabolites but weakly with SCFAs. The abundance of Rothia and Actinomyces was markedly positively correlated with 4-methylcatechol and guaiacol (p < 0.05) and negatively correlated with norvaline (p < 0.05). L-Norvaline inhibited the content of Arg-1 in a concentration-dependent manner. Compared with the L-Norvaline or doxorubicin hydrochloride (DOX) group, the proliferation abilities of 4 T1 cells were the lowest in the L-Norvaline combined with DOX (p < 0.05). The apoptosis rate increased (p < 0.05). Conclusions: Faecal metabolites and microbiota were significantly altered in breast cancer. Levels of differential metabolites (i.e. Norvaline) were significantly correlated with the abundance of differential microbiota. L-Norvaline combined with DOX could clearly inhibit the proliferation activity of breast cancer cells. Significance and impact of study: This might provide clues to uncover potential biomarkers for breast cancer diagnosis and treatment.
L-Norvaline, a new therapeutic agent against Alzheimer's disease
Neural Regen Res 2019 Sep;14(9):1562-1572.PMID:31089055DOI:10.4103/1673-5374.255980.
Growing evidence highlights the role of arginase activity in the manifestation of Alzheimer's disease (AD). Upregulation of arginase was shown to contribute to neurodegeneration. Regulation of arginase activity appears to be a promising approach for interfering with the pathogenesis of AD. Therefore, the enzyme represents a novel therapeutic target. In this study, we administered an arginase inhibitor, L-Norvaline (250 mg/L), for 2.5 months to a triple-transgenic model (3×Tg-AD) harboring PS1M146V, APPSwe, and tauP301L transgenes. Then, the neuroprotective effects of L-Norvaline were evaluated using immunohistochemistry, proteomics, and quantitative polymerase chain reaction assays. Finally, we identified the biological pathways activated by the treatment. Remarkably, L-Norvaline treatment reverses the cognitive decline in AD mice. The treatment is neuroprotective as indicated by reduced beta-amyloidosis, alleviated microgliosis, and reduced tumor necrosis factor transcription levels. Moreover, elevated levels of neuroplasticity related postsynaptic density protein 95 were detected in the hippocampi of mice treated with L-Norvaline. Furthermore, we disclosed several biological pathways, which were involved in cell survival and neuroplasticity and were activated by the treatment. Through these modes of action, L-Norvaline has the potential to improve the symptoms of AD and even interferes with its pathogenesis. As such, L-Norvaline is a promising neuroprotective molecule that might be tailored for the treatment of a range of neurodegenerative disorders. The study was approved by the Bar-Ilan University Animal Care and Use Committee (approval No. 82-10-2017) on October 1, 2017.
Reports of L-Norvaline Toxicity in Humans May Be Greatly Overstated
Brain Sci 2019 Dec 17;9(12):382.PMID:31861122DOI:10.3390/brainsci9120382.
Recently, a study published in "Toxicology In Vitro" (Kate Samardzic and Kenneth J. Rodgers) was entitled: "Cytotoxicity and Mitochondrial Dysfunction Caused by the Dietary Supplement L-Norvaline". The title may be greatly overstated, and here we provide several arguments showing that norvaline is not as toxic as reported.
Combination of L-Arginine and L-Norvaline protects against pulmonary fibrosis progression induced by bleomycin in mice
Biomed Pharmacother 2019 May;113:108768.PMID:30889486DOI:10.1016/j.biopha.2019.108768.
Pulmonary fibrosis (PF) progression may be involved with arginine (Arg) metabolism and immune balance. The present study aimed to explore the effects of L-Arginine (L-Arg) and L-Norvaline (L-Nor) on bleomycin (BLM)-induced PF in mice, meanwhile, and observe dynamic changes of Arg metabolism, immune balance and crosstalk between them in PF progression. Followed intratracheal instillation of BLM or saline, Kunming mice were treated orally with saline, L-Arg, L-Nor and L-Arg + L-Nor three times a day. And the mice were sacrificed on Day 3, 14 and 28 after treatment. Changes of body weight, lung index, lung hydroxyproline and histopathology were analyzed to evaluate the PF degree. Peripheral blood Arg, Citrulline (Cit), Ornithine (Orn) and Proline (Pro), lung NO, NOS and arginase were analyzed to evaluate the Arg metabolism. Peripheral blood Tregs, Th17 and γδT cells were analyzed to evaluate the immune balance. Our data showed that combination of L-Arg and L-Nor dynamically reversed the weight loss, decreased lung index and hydroxyproline, and improved lung histopathological damages induced by BLM. The combination dynamically and significantly rectified Tregs, Th17, γδT and Tregs/Th17 abnormal changes. Meanwhile, these disorders of peripheral blood Arg, Cit, Orn, Pro, Orn/Cit and Pro/Orn, and lung NO, iNOS and TNOS were also improved accordingly. These results demonstrated that combination of L-Arg and L-Nor had inhibitory effects on BLM-induced PF progression, possibly due to their corrective action on immune imbalance, Arg metabolism disorder and crosstalk abnormality in the progression of PF.