Neotuberostemonine
(Synonyms: 新对叶百部碱) 目录号 : GC36720
An alkaloid with diverse biological activities
Cas No.:143120-46-1
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
Neotuberostemonine is an alkaloid originally isolated from S. tuberosa that has diverse biological activities.1,2,3 It inhibits LPS-induced increases in inducible nitric oxide synthase (iNOS) protein levels and NO production in RAW 264.7 cells when used at a concentration of 100 ?M.1 Neotuberostemonine (50 ?M) inhibits RANKL-induced osteoclast differentiation of RAW 264.7 cells.2 It reduces the citric acid-induced cough reflex in conscious guinea pigs when administered at a dose of 133 ?mol/kg.3 Neotuberostemonine (40 mg/kg) inhibits pulmonary collagen deposition and fibrosis, as well as bronchoalveolar lavage fluid (BALF) monocyte and lymphocyte infiltration in a mouse model of bleomycin-induced pulmonary fibrosis.1
1.Xiang, J., Cheng, S., Feng, T., et al.Neotuberostemonine attenuates bleomycin-induced pulmonary fibrosis by suppressing the recruitment and activation of macrophagesInt. Immunopharmacol.36158-164(2016) 2.Yun, J., Lee, K.Y., and Park, B.Neotuberostemonine inhibits osteoclastogenesis via blockade of NF-kB pathwayBiochimie15781-91(2019) 3.Chung, H.-S., Hon, P.-M., Lin, G., et al.Antitussive activity of Stemona alkaloids from Stemona tuberosaPlanta Med.69(10)914-920(2003)
| Cas No. | 143120-46-1 | SDF | |
| 别名 | 新对叶百部碱 | ||
| Canonical SMILES | CC[C@@H]1[C@]2([H])[C@]3([H])[C@](C[C@]([C@](O4)([H])C[C@H](C)C4=O)([H])N3CCCC2)([H])[C@@]([C@@H]5C)([H])[C@]1([H])OC5=O | ||
| 分子式 | C22H33NO4 | 分子量 | 375.5 |
| 溶解度 | DMSO: 10 mM | 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 | 2.6631 mL | 13.3156 mL | 26.6312 mL |
| 5 mM | 0.5326 mL | 2.6631 mL | 5.3262 mL |
| 10 mM | 0.2663 mL | 1.3316 mL | 2.6631 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。
Neotuberostemonine inhibits osteoclastogenesis via blockade of NF-κB pathway
Biochimie 2019 Feb;157:81-91.PMID:30439408DOI:10.1016/j.biochi.2018.11.008.
Osteoporosis has been attributed to low bone mass arising from cellular communications between bone formation and bone resorption. Osteoclastogenesis is induced by M-CSF and RANKL in hematopoietic lineage cells. Once RANK/RANKL complex is formed, TRAF6 is recruited and triggers the activation of NF-κB pathway and the expression of osteoclast-related genes including NFATc1. Neotuberostemonine (NTS) is an active compound isolated from Stemona tuberosa Lour. Pharmacologically, NTS has been known to possess antitussive, anti-fibrotic and anti-inflammatory activities through regulation of macrophage. However, the influence of NTS to osteoclastogenesis has not been reported. The purpose of this study is to investigate whether NTS can modulate the osteoclastogenesis induced by RANKL or cancer cells. We found that NTS inhibits RANKL- or cancer cell-mediated osteoclastogenesis via blockade of TRAF6 and NF-κB activation. NTS also impairs the formation of F-actin ring structure, an important feature of osteoclast differentiation and function. These results indicate that NTS can be a preventive and therapeutic candidate for bone-related disease and that NTS provides insights underlying molecular mechanisms that influence osteoclastogenesis.
Neotuberostemonine attenuates bleomycin-induced pulmonary fibrosis by suppressing the recruitment and activation of macrophages
Int Immunopharmacol 2016 Jul;36:158-164.PMID:27144994DOI:10.1016/j.intimp.2016.04.016.
Neotuberostemonine (NTS) is one of the main antitussive alkaloids in the root of Stemona tuberosa Lour. This study aimed to investigate the effects of NTS on bleomycin (BLM)-induced pulmonary fibrosis in mice and the underlying mechanism. After BLM administration, NTS were orally administered to mice at 20 and 40mg/kg per day from days 8 to 21, with nintedanib as a positive control. The effect of NTS on BLM-induced mice was assessed via histopathological examination by HE and Masson's trichrome staining, TGF-β1 level and macrophage recruitment by immunohistochemical staining, expression of profibrotic media and M1/M2 polarization by western blot. RAW 264.7 cells were used to evaluate whether NTS (1, 10, 100μM) directly affected macrophages. The results revealed that NTS treatment significantly ameliorated lung histopathological changes and decreased inflammatory cell counts in the bronchoalveolar lavage fluid. The over-expression of collagen, α-SMA and TGF-β1 was reduced by NTS. Furthermore, NTS markedly lowered the expression of MMP-2 and TIMP-1 while raised the expression of MMP-9. A further analysis showed that NTS was able to decrease the recruitment of macrophages and to inhibit the M2 polarization in mice lung tissues. The experiment in vitro showed that NTS significantly reduced the arginase-1 (marker for M2) expression in a dose-dependent manner but down-regulated the iNOS (marker for M1) expression only at 100μM. In conclusion, our study demonstrated for the first time that NTS has a significant protective effect on BLM-induced pulmonary fibrosis through suppressing the recruitment and M2 polarization of macrophages.
Neotuberostemonine inhibits the differentiation of lung fibroblasts into myofibroblasts in mice by regulating HIF-1α signaling
Acta Pharmacol Sin 2018 Sep;39(9):1501-1512.PMID:29645000DOI:10.1038/aps.2017.202.
Pulmonary fibrosis may be partially the result of deregulated tissue repair in response to chronic hypoxia. In this study we explored the effects of hypoxia on lung fibroblasts and the effects of Neotuberostemonine (NTS), a natural alkaloid isolated from Stemona tuberosa, on activation of fibroblasts in vitro and in vivo. PLFs (primary mouse lung fibroblasts) were activated and differentiated after exposure to 1% O2 or treatment with CoCl2 (100 μmol/L), evidenced by markedly increased protein or mRNA expression of HIF-1α, TGF-β, FGF2, α-SMA and Col-1α/3α, which was blocked after silencing HIF-1α, suggesting that the activation of fibroblasts was HIF-1α-dependent. NTS (0.1-10 μmol/L) dose-dependently suppressed hypoxia-induced activation and differentiation of PLFs, whereas the inhibitory effect of NTS was abolished by co-treatment with MG132, a proteasome inhibitor. Since prolyl hydroxylation is a critical step in initiation of HIF-1α degradation, we further showed that NTS treatment reversed hypoxia- or CoCl2-induced reduction in expression of prolyl hydroxylated-HIF-1α. With hypoxyprobe immunofiuorescence staining, we showed that NTS treatment directly reversed the lower oxygen tension in hypoxia-exposed PLFs. In a mouse model of lung fibrosis, oral administration of NTS (30 mg·kg-1·d-1, for 1 or 2 weeks) effectively attenuated bleomycin-induced pulmonary fibrosis by inhibiting the levels of HIF-1α and its downstream profibrotic factors (TGF-β, FGF2 and α-SMA). Taken together, these results demonstrate that NTS inhibits the protein expression of HIF-1α and its downstream factors TGF-β, FGF2 and α-SMA both in hypoxia-exposed fibroblasts and in lung tissues of BLM-treated mice. NTS with anti-HIF-1α activity may be a promising pharmacological agent for the treatment of pulmonary fibrosis.
Pharmacokinetics, biodistribution and excretion studies of Neotuberostemonine, a major bioactive alkaloid of Stemona tuberosa
Fitoterapia 2016 Jul;112:22-9.PMID:27179627DOI:10.1016/j.fitote.2016.05.003.
Neotuberostemonine is a potent antitussive alkaloid extracted from Stemona tuberosa. However, the pharmacokinetics, tissue distribution and excretion of pure Neotuberostemonine have not been reported. The present study was aimed to investigate the pharmacokinetic parameters of Neotuberostemonine by developing an ultra-high performance liquid chromatography-tandem mass spectrometry method. Neotuberostemonine and tetrahydropalmatine (internal standard, IS) in bio-samples were extracted by protein precipitation with methanol and successfully separated on a Zorbax Extend C18 column by using a mobile phase of acetonitrile and a mixture of 0.1% formic acid and 5mM ammonium acetate. The detection was performed by using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/z 376.1→302.0 for Neotuberostemonine and 355.8→192.0 for IS. After oral administration of Neotuberostemonine in rats, the Cmax and AUC0-∞ were 11.37ng/mL and 17.68ng·h/mL at 20mg/kg and 137.6ng/mL and 167.4ng·h/mL at 40mg/kg, and the t1/2 were 2.28 and 3.04h at 20 and 40mg/kg, respectively. The high Neotuberostemonine concentrations were found in intestine, stomach and liver, and there was no long-term accumulation of Neotuberostemonine in tissues. Total recoveries of Neotuberostemonine were only 0.90% (0.19% in bile, 0.05% in urine and 0.66% in feces), which might be resulted from the intestine and liver first-pass effects, indicating that Neotuberostemonine may be mainly excreted as its metabolites. All above results would provide helpful information for the further pharmacological and clinical studies of Neotuberostemonine and the crude drug.
Metabolic profiles of Neotuberostemonine and tuberostemonine in rats by high performance liquid chromatography/quadrupole time-of-flight mass spectrometry
J Pharm Biomed Anal 2017 Jul 15;141:210-221.PMID:28448890DOI:10.1016/j.jpba.2017.04.018.
Neotuberostemonine (NS) and tuberostemonine (TS), a pair of stereoisomers, are the active components contained in Stemona tuberosa, an antitussive herbal medicine in China. Two isomers have different pharmacological efficacies, which will be related with their in vivo disposition. However, the metabolic fates of NS and TS remain unknown. A method of high performance liquid chromatography/quadrupole time-of-flight mass spectrometry coupled with mass detect filter technique was established to investigate the metabolites in rat plasma, bile, urine, and feces after oral administration of the equal doses of NS and TS. The results showed that NS produced 48 phase I metabolites, including NS, 3 hydrolyzed, 14 hydroxylated, 20 monohydrolyzed+hydroxylated and 10 dihydrolyzed+hydroxylated metabolites. The number of detected NS metabolites was 11, 39, 22 and 30 in plasma, bile, urine and feces. TS yielded 23 phase I metabolites, including TS, 3 hydrolyzed, 7 hydroxylated, 9 monohydrolyzed+hydroxylated and 3 dihydrolyzed+hydroxylated metabolites. Besides, TS yielded 9 phase II metabolites, including 1 glucuronic acid and 2 glutathione conjugates, and the later further degraded and modified into cysteine-glycine, cysteine and N-acetylcysteine conjugates. The number of detected TS metabolites was 9, 24, 24 and 15 in plasma, bile, urine and feces. Different metabolic patterns may be one of the main reasons leading to different pharmacological effects of NS and TS.