Veratramine
(Synonyms: 黎芦碱; NSC17821; NSC23880) 目录号 : GC37895
An inhibitor of hedgehog signaling
Cas No.:60-70-8
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
The hedgehog (Hh) signaling pathway, which is blocked by cyclopamine , plays a key role in morphogenesis and has potential applications in the treatment of cancer.1,2,3 Veratramine, a teratogenic steroidal alkaloid isolated from the corn lily (Veratrum sp.), is an analog of cyclopamine that can inhibit the Hh signaling-
1.Heretsch, P., Tzagkaroulaki, L., and Giannis, A.Cyclopamine and hedgehog signaling: Chemistry, biology, medical perspectivesAgnew. Chem. Int. Ed. Engl.49(20)3418-3427(2010) 2.Xu, F.G., Ma, Q.Y., and Wang, Z.Blockade of hedgehog signaling pathway as a therapeutic strategy for pancreatic cancerCancer Lett.283(2)119-124(2009) 3.Mahindroo, N., Punchihewa, C., and Fujii, N.Hedgehog-Gli signaling pathway inhibitors as anticancer agentsJ. Med. Chem.52(13)3829-3845(2009) 4.Tang, J., Li, H.L., Shen, Y.H., et al.Antitumor and antiplatelet activity of alkaloids from Veratrum dahuricumPhytother. Res.24(6)821-826(2010) 5.Nagata, R., Izumi, K., Iwata, S.i., et al.Mechanisms of veratramine-induced 5-HT syndrome in miceJpn. J. Pharmacol.55139-146(1991) 6.Fukuma, K.Actions of veratramine on the central nervous systemJpn. J. Pharmacol.5102-114(1956)
| Cas No. | 60-70-8 | SDF | |
| 别名 | 黎芦碱; NSC17821; NSC23880 | ||
| Canonical SMILES | O[C@H]1[C@H]([C@H](C2=C(C)C3=C(C=C2)[C@]4([H])CC=C(C[C@@H](O)CC5)[C@@]5(C)[C@@]4([H])C3)C)NC[C@@H](C)C1 | ||
| 分子式 | C27H39NO2 | 分子量 | 409.6 |
| 溶解度 | DMSO: ≥ 100 mg/mL (244.14 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 | 2.4414 mL | 12.207 mL | 24.4141 mL |
| 5 mM | 0.4883 mL | 2.4414 mL | 4.8828 mL |
| 10 mM | 0.2441 mL | 1.2207 mL | 2.4414 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。
Pharmacokinetics of Veratramine and Jervine from Alcohol Extracts of Radix Veratri
Comput Math Methods Med 2022 Jun 23;2022:8289548.PMID:35785141DOI:10.1155/2022/8289548.
Background: Chinese Materia Medica and Jiangsu New Medical College record that Radix Veratri root is Liliaceae Veratrum taliense Loses. f. and the root of Veratrum stenophyllum Diels. According to traditional Chinese medicine (TCM) example, Radix Veratri is a Liliaceae plant Veratrum taliense. Another literature pointed out that the aliases of Veratrum taliense and Veratrum angustifolia are both Radix Veratri, and their effects are basically the same. The main active ingredient of Veratrum is Veratramine, of which Veratramine and Jervine are higher in content, reaching 24.60% and 21.28% of the total alkaloids, respectively. Veratrum alkaloids are both toxic and effective ingredients. In addition to its good clinical efficacy, attention should also be paid to its pharmacokinetic characteristics in vivo. It is particularly important to study the pharmacokinetic characteristics of Veratramine and Jervine in vivo. Objective: The goal of this study was to develop a simple and effective method for measuring Veratramine and Jervine in rat plasma at the same time. This method was used to study the pharmacokinetic characteristics of Veratramine and Jervine in the alcohol extract of Radix Veratri in rats, to provide a reasonable basis for the clinical use of Radix Veratri. Methods: Eighteen SD rats were randomly assigned into three groups, half male and half female, and were given 0.04 g/kg, 0.08g/kg, and 0.16 g/kg Radix Veratri alcohol extract, respectively. Blood samples were collected at different time points and were analyzed by LC-MS/MS after protein precipitation. Bullatine was set as the internal standard; the plasma samples were extracted with ethyl acetate. After the sample was processed, acetonitrile-10 mM ammonium acetate, whose pH was adjusted to 8.8 with ammonia water, was taken as the mobile phase. Veratramine quantitative ion pair was 410.1⟶295.1m/z, Jervine quantitative ion pair was 426.2⟶114.1m/z, and Bullatine B (IS) quantitative ion pair was 438.2⟶420.1m/z. In the positive ion mode, the multireaction monitoring (MRM) mode was used to determine the blood concentration of Veratramine and Jervine. DAS 3.3.0 was used to calculate the relevant pharmacokinetic parameters. Results: Veratramine had a good linear relationship in the concentration range of 0.0745~18.2 ng/mL, and that of Jervine was 1.11~108 ng/mL. The correlation coefficient r of three consecutive batches of the standard curve was greater than 0.995. Veratramine's lower quantification limit was 0.745 ng/mL, Jervine's was 1.11 ng/mL, and precision and accuracy were both less than 15%. The accuracy of Veratramine was between 88.96% and 101.85%, and the accuracy of Jervine was between 92.96% and 104.50%. This method was adopted for the pharmacokinetic study of alcohol extracts of Radix Veratri. The results showed that only C max of Veratramine female rats did not show linear kinetic characteristics in the dose range of Radix Veratri alcohol extract from 0.04 g/kg to 0.16 g/kg. For AUC0-t and C max of Veratramine and Jervine, it could not determine whether the Radix Veratri alcohol extract showed linear kinetic characteristics within the dosage range of 0.04 g/kg~0.16 g/kg. Veratramine and Jervine showed obvious gender differences in the absorption and elimination stages. The absorption rate of Veratramine and Jervine by male mice was about 10 times higher than that of female mice, and the elimination rate of male mice is about 20 times lower than that of female mice. It was suggested that the clinical application of the steroidal alkaloids Veratramine and Jervine in Radix Veratri required rational use of drugs based on gender. Conclusion: An LC-MS/MS analysis method suitable for the pharmacokinetic study of Veratramine and Jervine in Radix Veratri in SD rats was established to provide a basis for in vivo pharmacokinetic studies. The pharmacokinetic characteristics of Veratramine and Jervine in the alcohol extract of Radix Veratri were significantly different in female and male rats. During the clinical use of Radix Veratri, it should pay close attention to the obvious gender differences that may occur after the medication.
Veratramine ameliorates pain symptoms in rats with diabetic peripheral neuropathy by inhibiting activation of the SIGMAR1-NMDAR pathway
Pharm Biol 2022 Dec;60(1):2145-2154.PMID:36373991DOI:10.1080/13880209.2022.2136207.
Context: Veratramine may have a potential therapeutic effect for diabetic peripheral neuropathy (DPN). Objective: To evaluate whether Veratramine ameliorates neuropathic pain in a rat diabetic model. Materials and methods: Sprague-Dawley rats were used for a diabetic model induced by a streptozotocin + high-fat diet. Two months after the induction of the diabetic model, the rats with DPN were screened according to the mechanical pain threshold. The rats with DPN were divided into a model group (n = 12) and a treated group (n = 12). Rats with diabetes, but without peripheral neuropathy, were used in the vehicle group (n = 9). The treatment group received 50 μg/kg Veratramine via the tail vein once a day for 4 weeks. During modelling and treatment, rats in all three groups were fed a high-fat diet. Results: The mechanical withdrawal threshold increased from 7.5 ± 1.9 N to 17.9 ± 2.6 N in DPN rats treated with Veratramine. The tolerance time of the treated group to hot and cold ectopic pain increased from 11.8 ± 4.2 s and 3.4 ± 0.8 s to 20.4 ± 4.1 s and 5.9 ± 1.7 s, respectively. Veratramine effectively alleviated L4-L5 spinal cord and sciatic nerve pathological injury. Veratramine inhibited the expression of SIGMAR1 and the phosphorylation of the N-methyl-d-aspartate receptor (NMDAR) Ser896 site in spinal cord tissue, as well as inhibited the formation of SIGMAR1-NMDAR and NMDAR-CaMKII complexes. Discussion and conclusions: Veratramine may alleviate the occurrence of pain symptoms in rats with DPN by inhibiting activation of the SIGMAR1-NMDAR pathway.
Anticancer effects of Veratramine via the phosphatidylinositol-3-kinase/serine-threonine kinase/mechanistic target of rapamycin and its downstream signaling pathways in human glioblastoma cell lines
Life Sci 2022 Jan 1;288:120170.PMID:34826438DOI:10.1016/j.lfs.2021.120170.
Aims: Antitumor effects of Veratramine in prostate and liver cancers has been investigated, but it is still unclear whether Veratramine can be used as an effective therapeutic agent for glioma. The aim of this study was to evaluate the potential pharmacological mechanism of Veratramine in glioma. Main methods: Using four types of human glioblastoma cell lines, including A172, HS-683, T98G, and U-373-MG the dose-dependent antitumor effect of Veratramine was evaluated. The cytotoxicity and cell proliferation were examined by CCK-8, and cell proliferation was further confirmed by anchorage-independent colony formation assay. The cell cycle distribution and apoptotic rate was assessed by flow cytometry, and apoptosis was further evaluated by apoptosis assay. The migration and invasiveness capacity were analyzed by using transwell. Protein and mRNA levels of related factors were determined by western blotting and RT-qPCR, respectively. Key findings: Veratramine markedly induced apoptosis, suppressed the cell proliferation via the cell cycle G0/G1 phase arrest, and reduced the capacity for the migration and invasion in human glioblastoma multiforme cell lines. Moreover, Veratramine was sufficient to affect the phosphatidylinositol-3-kinase/serine-threonine kinase/mechanistic target of rapamycin signaling pathway and its downstream Mdm2/p53/p21 pathway in human glioblastoma cell lines. Significance: Antitumor effects of Veratramine in suppression of glioma progression was mediated by the regulation of PI3K/Akt/mTOR and Mdm2/p53/p21 signaling pathway.
Gender-Dependent Pharmacokinetics of Veratramine in Rats: In Vivo and In Vitro Evidence
AAPS J 2016 Mar;18(2):432-44.PMID:26791530DOI:10.1208/s12248-016-9870-9.
Veratramine, a major alkaloid from Veratrum nigrum L., has distinct anti-tumor and anti-hypertension effects. Our previous study indicated that Veratramine had severe toxicity toward male rats. In order to elucidate the underling mechanism, in vivo pharmacokinetic experiments and in vitro mechanistic studies have been conducted. Veratramine was administrated to male and female rats intravenously via the jugular vein at a dose of 50 μg/kg or orally via gavage at 20 mg/kg. As a result, significant pharmacokinetic differences were observed between male and female rats after oral administration with much lower concentrations of Veratramine and 7-hydroxyl-veratramine and higher concentrations of veratramine-3-O-sulfate found in the plasma and urine of female rats. The absolute bioavailability of Veratramine was 0.9% in female rats and 22.5% in male rats. Further experiments of Veratramine on Caco-2 cell monolayer model and in vitro incubation with GI content or rat intestinal subcellular fractions demonstrated that its efficient passive diffusion mediated absorption with minimal intestinal metabolism, suggesting no gender-related difference during its absorption process. When Veratramine was incubated with male or female rat liver microsomes/cytosols, significant male-predominant formation of 7-hydroxyl-veratramine and female-predominant formation of veratramine-3-O-sulfate were observed. In conclusion, the significant gender-dependent hepatic metabolism of Veratramine could be the major contributor to its gender-dependent pharmacokinetics.
Veratramine suppresses human HepG2 liver cancer cell growth in vitro and in vivo by inducing autophagic cell death
Oncol Rep 2020 Aug;44(2):477-486.PMID:32468056DOI:10.3892/or.2020.7622.
Liver cancer is the second leading cause of cancer‑related deaths. Traditional therapeutic strategies, such as chemotherapy, targeted therapy and interventional therapy, are inefficient and are accompanied by severe side effects for patients with advanced liver cancer. Therefore, it is crucial to develop a safer more effective drug to treat liver cancer. Veratramine, a known natural steroidal alkaloid derived from plants of the lily family, exerts anticancer activity in vitro. However, the underlying mechanism and whether it has an antitumor effect in vivo remain unknown. In the present study, the data revealed that Veratramine significantly inhibited HepG2 cell proliferation, migration and invasion in vitro. Moreover, it was revealed that Veratramine induced autophagy‑mediated apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway, which partly explained the underlying mechanism behind its antitumor activity. Notably, the results of in vivo experiments also revealed that Veratramine treatment (2 mg/kg, 3 times a week for 4 weeks) significantly inhibited subcutaneous tumor growth of liver cancer cells, with a low systemic toxicity. Collectively, the results of the present study indicated that Veratramine efficiently suppressed liver cancer HepG2 cell growth in vitro and in vivo by blocking the PI3K/Akt/mTOR signaling pathway to induce autophagic cell death. Veratramine could be a potential therapeutic agent for the treatment of liver cancer.