Mitraphylline
(Synonyms: 帽柱叶碱) 目录号 : GC40056
An alkaloid with anti-inflammatory and antiproliferative properties
Cas No.:509-80-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Mitraphylline is the major pentacyclic oxindolic alkaloid found in U. tomentosa and has anti-inflammatory and antiproliferative properties. It reduces production of nitric oxide (NO), IL-8, IL-6, and TNF-α as well as expression of inducible nitric oxide synthase (iNOS) in LPS-activated human neutrophils. Mitraphylline inhibits the growth of SKN-BE(2) neuroblastoma, GAMG glioblastoma, MHH-ES-1 Ewing's sarcoma, and MT-3 breast cancer cells (IC50s = 12.3, 20, 17.15, and 11.18 μM, respectively). In vivo, mitraphylline (30 mg/kg per day) inhibits LPS-induced release of IL-1α, IL-1β, IL-17, and TNF-α in mouse serum.
| Cas No. | 509-80-8 | SDF | |
| 别名 | 帽柱叶碱 | ||
| Canonical SMILES | O=C1NC2=C(C=CC=C2)[C@]31CCN4C[C@]5([H])[C@H](C)OC=C(C(OC)=O)[C@@]5([H])C[C@]43[H] | ||
| 分子式 | C21H24N2O4 | 分子量 | 368.4 |
| 溶解度 | DMF: 5 mg/ml,DMSO: 5 mg/ml,DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml,Ethanol: slightly soluble | 储存条件 | 4°C, away from moisture and 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 | 2.7144 mL | 13.5722 mL | 27.1444 mL |
| 5 mM | 0.5429 mL | 2.7144 mL | 5.4289 mL |
| 10 mM | 0.2714 mL | 1.3572 mL | 2.7144 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。
Mitraphylline inhibits lipopolysaccharide-mediated activation of primary human neutrophils
Phytomedicine 2016 Feb 15;23(2):141-8.PMID:26926175DOI:10.1016/j.phymed.2015.12.015.
Background: Mitraphylline (MTP) is the major pentacyclic oxindolic alkaloid presented in Uncaria tomentosa. It has traditionally been used to treat disorders including arthritis, heart disease, cancer, and other inflammatory diseases. However, the specific role of MTP is still not clear, with more comprehensivestudies, our understanding of this ancient herbal medicine will continue growing. Hypothesis/purpose: Some studies provided its ability to inhibit proinflamatory cytokines, such as TNF-α, through NF-κB-dependent mechanism. TNF-α primes neutrophils and modulates phagocytic and oxidative burst activities in inflammatory processes. Since, neutrophils represent the most abundant pool of leukocytes in human blood and play a crucial role in inflammation, we aimed to determine the ability of MTP to modulate neutrophil activation and differentially regulate inflammatory-related cytokines. Methods: To determine the mechanism of action of MTP, we investigated the effects on LPS-activated human primary neutrophils responses including activation surface markers by FACS and the expression of inflammatory cytokines, measured by real time PCR and ELISA. Results: Treatment with MTP reduced the LPS-dependent activation effects. Activated neutrophils (CD16(+)CD62L(-)) diminished after MTP administration. Moreover, proinflamatory cytokines (TNF-α, IL-6 or IL-8) expression and secretion were concomitantly reduced, similar to basal control conditions. Conclusion: Taken together, our results demonstrate that MTP is able to elicit an anti-inflammatory response that modulates neutrophil activation contributing to the attenuation of inflammatory episodes. Further studies are need to characterize the mechanism by which MTP can affect this pathway that could provide a means to develop MTP as new candidate for inflammatory disease therapies.
Isolation of Mitraphylline from Uncaria tomentosa (Willd. ex Schult.) DC. barks and development of spectrophotometric method for total alkaloids determination in Cat's Claw samples
Phytochem Anal 2020 Mar;31(2):262-272.PMID:31769108DOI:10.1002/pca.2891.
Introduction: The usual quality control for Uncaria tomentosa (Willd. ex Schult.) DC. barks requires highly specific analytical standards and methods based on high-performance liquid chromatography (HPLC), which impacts the costs of the analytical process and the final products. Objective: To obtain an analytical reference standard of Mitraphylline by isolation from U. tomentosa barks and develop a spectrophotometric method for determination of total alkaloids in samples of U. tomentosa. Methodology: An alkaloid-enriched extract was obtained by acid-base partition and Mitraphylline was selectively precipitated using an 80:20 v/v toluene/hexane solution. The compound was characterised by HPLC-UV/DAD (diode-array detector), mass spectrometry, UV-visible, infrared (IR) and 1 H- and 13 C-nuclear magnetic resonance (NMR) spectroscopy. Sample preparation for the spectrophotometric method consisted of an extraction with boiling methanol (3 × 10 mL, 15 min), followed by a strong cation exchange solid phase extraction (SCX-SPE) clean-up. Results: Mitraphylline with a purity of 98% was isolated in 0.05% m/m yield. All characterisation results were in agreement with previous published data. The spectrophotometric method showed linear range between 0.40 and 20 μg/mL; limits of detection and quantification of 0.15 and 0.49 μg/mg, respectively; dispersion of results lower than 5% for repeatability and intermediate precision; statistically proven accuracy by comparison with reference values obtained by Soxhlet and an HPLC-UV/DAD method; and robustness in relation to sample mass extracted and extraction time. Conclusion: The methods developed to obtain Mitraphylline analytical standard from U. tomentosa barks and to determine total alkaloids by spectrophotometry provided a cheaper and faster quality control alternative for U. tomentosa samples.
Neuroprotective potential of the oxindole alkaloids isomitraphylline and Mitraphylline in human neuroblastoma SH-SY5Y cells
3 Biotech 2020 Dec;10(12):517.PMID:33194521DOI:10.1007/s13205-020-02535-4.
The purified oxindole alkaloids, isomitraphylline and Mitraphylline from Uncaria perrottetii, revealed their ability to break amyloid aggregates in vitro suggesting their therapeutic potentials in Alzheimer's disease (AD). Thioflavin-T assay for assessing amyloid-beta (Aβ) aggregation of these alkaloids exhibited inhibitions at 60.321% ± 2.61 (50 μM) for isomitraphylline and 43.17% ± 3.48 (50 μM) for Mitraphylline. Neuroprotective effects were elaborated against Aβ-induced SH-SY5Y cells at 20 μM and 10 μM for isomitraphylline, and 20 μM for Mitraphylline. In addition, both alkaloids attenuated and protected the H2O2-induced SH-SY5Y cell cytotoxicity at 20 μM. The intracellular ROS levels of SH-SY5Y cells from H2O2-induced oxidative stress were reduced at 20 μM and 10 μM, and the mitochondrial membrane potentials of Aβ-induced SH-SY5Y cells were protected at 20 μM. The overall results suggested the potentials of both alkaloids to target certain pathological biomarkers of AD and could be further investigated as therapeutic or preventive drug leads against AD.
Anti-inflammatory activity of Mitraphylline isolated from Uncaria tomentosa bark
J Ethnopharmacol 2012 Oct 11;143(3):801-4.PMID:22846434DOI:10.1016/j.jep.2012.07.015.
Ethnopharmacological relevance: Uncaria tomentosa (Willd. ex Roem. & Schult.) DC. (Rubiaceae) is widely used by populations living in South America to treat many ailments associated with inflammatory disorders. Mitraphylline was shown to be the major pentacyclic oxindolic alkaloid present in the bark chloroformic extract of this plant. Its activity against cytokines involved in inflammation process was tested in a murine model in vivo. Materials and methods: Mice received Mitraphylline once a day for 3 days at 30 mg/kg/day by oral route. Then, they were subjected to bacterial lipopolysaccharide (LPS) endotoxin (15 mg/kg) and the LPS-induced production of 16 different cytokines was determined by Elisa multiplex. Control group received dexamethasone orally at 2mg/kg/day. Toxicity on K565 cells and murine peritoneal macrophages, in vitro, at doses up to 100 μM was monitored by XTT-colorimetric assay. Results and conclusions: For the first time Mitraphylline was tested in vivo against a large range of cytokines that play a crucial role in inflammation. Mitraphylline inhibited around 50% of the release of interleukins 1α, 1β, 17, and TNF-α. This activity was similar to dexamethasone. It also reduced almost 40% of the production of interleukin 4 (IL-4) while the corticoid did not. Lastly it did not show any toxicity on K565 cells nor murine macrophages at doses up to 100 μM.
Evaluation of in vitro absorption, distribution, metabolism, and excretion (ADME) properties of mitragynine, 7-hydroxymitragynine, and Mitraphylline
Planta Med 2014 May;80(7):568-76.PMID:24841968DOI:10.1055/s-0034-1368444.
Mitragyna speciosa (kratom) is a popular herb in Southeast Asia, which is traditionally used to treat withdrawal symptoms associated with opiate addiction. Mitragynine, 7-hydroxymitragynine, and Mitraphylline are reported to be the central nervous system active alkaloids which bind to the opiate receptors. Mitraphylline is also present in the bark of Uncaria tomentosa (cat's claw). Several therapeutic properties have been reported for these compounds but limited information is available on the absorption and distribution properties. This study focuses on evaluating the absorption, distribution, metabolism, and excretion (ADME) properties of these compounds and their effect on major efflux transporter P-glycoprotein, using in vitro methods. Quantitative analysis was performed by the Q-TOF LC-MS system. Mitragynine was unstable in simulated gastric fluid with 26 % degradation but stable in simulated intestinal fluid. 7-Hydroxymitragynine degraded up to 27 % in simulated gastric fluid, which could account for its conversion to mitragynine (23 %), while only 6 % degradation was seen in simulated intestinal fluid. Mitraphylline was stable in simulated gastric fluid but unstable in simulated intestinal fluid (13.6 % degradation). Mitragynine and 7-hydroxymitragynine showed moderate permeability across Caco-2 and MDR-MDCK monolayers with no significant efflux. However, Mitraphylline was subjected to efflux mediated by P-glycoprotein in both Caco-2 and MDR-MDCK monolayers. Mitragynine was found to be metabolically stable in both human liver microsomes and S9 fractions. In contrast, both 7-hydroxymitragynine and Mitraphylline were metabolized by human liver microsomes with half-lives of 24 and 50 min, respectively. All three compounds exhibited high plasma protein binding (> 90 %) determined by equilibrium dialysis. Mitragynine and 7-hydroxymitragynine inhibited P-glycoprotein with EC50 values of 18.2 ± 3.6 ?M and 32.4 ± 1.9 ?M, respectively, determined by the calcein-AM fluorescent assay, while no inhibition was seen with Mitraphylline. These data indicate the possibility of a drug interaction if mitragynine and 7-hydroxymitragynine are coadministered with drugs that are P-glycoprotein substrates.