Hirsuteine
(Synonyms: 去氢毛钩藤碱) 目录号 : GC36228
An indole alkaloid with neuroprotective activities
Cas No.:35467-43-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Hirsuteine is an indole alkaloid that has been found in U. sinensis and has neuroprotective activities.1,2 It reduces glutamate-induced cytotoxicity in primary rat cerebellar granule neurons when used at concentrations ranging from 100 to 300 ?M.1 Hirsuteine (1-100 ?M) inhibits nicotine-induced dopamine release in PC12 cells.2
1.Shimada, Y., Goto, H., Itoh, T., et al.Evaluation of the protective effects of alkaloids isolated from the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death in cultured cerebellar granule cells from ratsJ. Pharm. Pharmacol.51(6)715-722(1999) 2.Watano, T., Nakazawa, K., Obama, T., et al.Non-competitive antagonism by hirsuteine of nicotinic receptor-mediated dopamine release from rat pheochromocytoma cellsJpn. J. Pharmacol.61(4)351-356(1993)
| Cas No. | 35467-43-7 | SDF | |
| 别名 | 去氢毛钩藤碱 | ||
| Canonical SMILES | O=C(OC)/C([C@H]([C@H](CN1CC2)C=C)C[C@]1([H])C3=C2C(C=CC=C4)=C4N3)=C/OC | ||
| 分子式 | C22H26N2O3 | 分子量 | 366.45 |
| 溶解度 | DMSO : 100 mg/mL (272.89 mM; Need ultrasonic) | 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 | 2.7289 mL | 13.6444 mL | 27.2889 mL |
| 5 mM | 0.5458 mL | 2.7289 mL | 5.4578 mL |
| 10 mM | 0.2729 mL | 1.3644 mL | 2.7289 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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。
Effects of Hirsuteine on MDA-MB-453 breast cancer cell proliferation
Oncol Lett 2022 Nov 9;25(1):4.PMID:36419752DOI:10.3892/ol.2022.13590.
Hirsuteine is extracted from Uncaria rhynchophylla, the bark of which has traditionally been used to treat hypertension, cancer, convulsions, hemorrhage, auto-immune disorders, and other ailments. The anticancer properties of Hirsuteine are of significant importance to the research community; however, its underlying mechanism of action is not well understood. The aim of the present study was to examine the antiproliferative ability of Hirsuteine using human breast cancer MDA-MB-453 cells and to determine the underlying molecular mechanism involved in its therapeutic efficacy. The effects of Hirsuteine on cell viability were determined using CCK-8 and colony formation assays, while apoptosis was assessed using flow cytometry. Cell cycle distribution was assessed using flow cytometry, and apoptotic cell quantification was performed using via Annexin V-FITC/PI staining and flow cytometry. Reverse transcription-quantitative PCR and western blotting were used to assess the expression of cell cycle progression and apoptosis associated genes and proteins. MDA-MB-453 cell proliferation was significantly reduced by Hirsuteine in a concentration and time-dependent manner. Hirsuteine-treated cells exhibited G2/M phase arrest, as evidenced by the increase in G2/M phase cells and a decrease in the G0/G1 phase cells, and this was related to cyclin B1 and CDK1 downregulation. Furthermore, Hirsuteine accelerated MDA-MB-453 cell apoptosis by downregulating Bcl-2 while upregulating cytoplasmic cytochrome c, Bax, Apaf1, cleaved caspase-3, and cleaved caspase-9 levels, which together drove apoptotic cell death. Thus, Hirsuteine suppressed MDA-MB-453 cancer cell proliferation by inducing cell cycle arrest and promoting apoptosis.
Metabolites identification and pharmacokinetic profile of Hirsuteine, a bioactive component in Uncaria in rats by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry
J Sep Sci 2022 Dec;45(23):4145-4157.PMID:36216761DOI:10.1002/jssc.202200452.
Hirsuteine is one of the major bioactive tetracyclic indole alkaloids found in Uncaria rhynchophylla (Miq.) Jacks, possessing a wide range of pharmacological activities including neuroprotective, anticonvulsant, antihypertensive, sedative and hypnotic, and so forth. The present study was undertaken to assess the metabolism and plasma pharmacokinetics of Hirsuteine in rats. After oral administration of Hirsuteine at the dose of 30 mg/kg, 13, 21, and 8 metabolites were detected in rat plasma, urine, and bile by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, respectively. Furthermore, plasma concentrations of Hirsuteine and its four metabolites, 4-hirsuteine N-oxide, 3,4-dehydrohirsuteine, 11-hydroxyhirsuteine, and 11-hydroxyhirsuteine-11-O-glucuronide were simultaneously quantified in rat plasma, using carbamazepine as the internal standard. The linear calibration curve of Hirsuteine was in the concentration range of 0.005-5.0 μg/ml. The lower limit of quantitation in the rat plasma was 5 ng/ml for Hirsuteine. This study is the first to comprehensively investigate the metabolism process of Hirsuteine and the pharmacokinetic profiles of Hirsuteine and its major metabolite, and will provide a scientific basis to further elucidate the pharmacodynamic material basis and therapeutic mechanism of Uncaria prescriptions.
Tissue Distribution of Hirsutine and Hirsuteine in Mice by Ultrahigh-Performance Liquid Chromatography-Mass Spectrometry
J Anal Methods Chem 2020 Apr 21;2020:7204315.PMID:32399311DOI:10.1155/2020/7204315.
Hirsutine and Hirsuteine were two alkaloid monomers extracted from the traditional Chinese medicine Uncaria rhynchophylla, which have pharmacological effects such as antihypertension, anti-infection, and heart protection. An ultrahigh-performance liquid chromatography-mass spectrometry was established for the determination of hirsutine and Hirsuteine in tissues (liver, kidney, heart, spleen, brain, and lung), and their absorption, distribution, and metabolism were studied for providing information on its pharmacological mechanism. UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) was used for chromatographic separation. The mobile phase was acetonitrile-0.1% formic acid, with a gradient elution, and the total run time was 4 min. Electrospray was used in the positive ion mode, and the multiple reaction monitoring (MRM) mode was for quantification. The acetonitrile precipitation method was used to remove protein-treated mouse plasma and tissue homogenate samples. In the concentration range of 2-5000 ng/g, hirsutine and Hirsuteine in tissues showed good linearity (r > 0.995), and the lower limit of quantification was 2 ng/g. In the plasma and liver tissues, the interday and intraday precision of hirsutine and Hirsuteine was less than 15%, the accuracy was between 90.9% and 110.1%, and the average recovery was better than 73.0%. The matrix effect was between 86.2% and 104.7%. The results showed that the precision, accuracy, recovery, and matrix effects meet the requirements for the study on the distribution of hirsutine and Hirsuteine. After intraperitoneal administration of 10 mg/kg hirsutine and Hirsuteine in mice, the distribution levels were highest in liver and kidney tissues, followed by the spleen and lung. Hirsutine and Hirsuteine were low in brain tissue, but had obvious distribution, suggesting that they may pass through the blood-brain barrier.
Simultaneous separation and determination of hirsutine and Hirsuteine by cyclodextrin-modified micellar electrokinetic capillary chromatography
Phytochem Anal 2020 Jan;31(1):112-118.PMID:31328320DOI:10.1002/pca.2871.
Introduction: Hirsutine and Hirsuteine are the main pharmacological activity ingredients of Uncaria rhynchophylla (UR), playing an important role in treating mental and cardiovascular diseases, such as Alzheimer's disease, hypertension, Parkinson's disease, potential anti-cancer activities and so on. Objective: To develop a cyclodextrin-modified micellar electrokinetic capillary chromatography (CD-MEKC) method for the simultaneous separation and determination of hirsutine and Hirsuteine from UR and its formulations. Methodology: The optimal method was developed by investigating influences of significant factors on the separation, and this method was successfully applied for the determination of hirsutine and Hirsuteine in UR and its formulations. Results: The optimal background electrolyte (BGE) consisted of 40 mM sodium dihydrogen phosphate (pH 7.0), 150 mM 2,6-dimethyl-β-cyclodextrin (DM-β-CD), 3 mM mono-(6-ethylenediamine-6-deoxy)-β-cyclodextrin (ED-β-CD), and 30 mM sodium cholate (SC). Under these conditions, hirsutine and Hirsuteine were successfully separated within 13 min at the separation voltage of 15 kV, temperature of 25°C and the detection wavelength of 224 nm. For the analytes, linear calibration curves were performed within the range 5.0-160.0 μg/mL. The limit of detection (LOD, S/N = 3) and the limit of quantitation (LOQ, S/N = 10) were 0.41, 1.42 μg/mL for hirsutine and 0.60, 2.17 μg/mL for Hirsuteine, respectively. The recoveries of three samples were from 97.9% to 102.3%. Conclusion: The method was successfully applied to the determination of hirsutine and Hirsuteine in UR and its formulations. Meanwhile, it provides an effective reference of the quality control of UR and its formulations.
Non-competitive antagonism by Hirsuteine of nicotinic receptor-mediated dopamine release from rat pheochromocytoma cells
Jpn J Pharmacol 1993 Apr;61(4):351-6.PMID:8320880DOI:10.1254/jjp.61.351.
Effects of Hirsuteine, an indole alkaloid extracted from Uncaria genus, on nicotine- and high K-induced responses were investigated in rat pheochromocytoma PC12 cells. Hirsuteine (300 nM-10 microM) inhibited dopamine release evoked by 100 microM nicotine in a concentration-dependent manner. Hirsuteine did not produce a parallel shift of the concentration-response relationship curve for nicotine, but reduced maximal dopamine release. Dopamine release evoked by 60 and 155 mM KCl was also inhibited by Hirsuteine, but the concentration necessary for significant inhibition was higher (more than 10 microM). Under whole cell voltage-clamp, Hirsuteine reversibly inhibited inward currents activated by 100 microM nicotine. The current inhibition was slightly accelerated by hyperpolarization. The results suggest that Hirsuteine non-competitively antagonizes nicotine-evoked dopamine release by blocking ion permeation through nicotinic receptor channel complexes. The blockade of Ca channels, which are activated during nicotine-evoked depolarization, may not play a major role in the antagonism.