Verproside
(Synonyms: 毛蕊花糖苷) 目录号 : GC37898
Verproside，一种从 Pseudolysimachion 属分离的梓醇衍生物环烯醚萜苷，通过 IKK/IκB 信号级联反应抑制 NF-κB 活化，抑制TNF-α 诱导的 MUC5AC 表达。Verproside具有有效的抗炎，抗氧化，抗伤害作用，并且在体内是一种有效的抗哮喘 /COPD 候选药物。
Cas No.:50932-20-2
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
Verproside, a catalpol derivative iridoid glycoside isolated from the genus Pseudolysimachion, represses TNF-α -induced MUC5AC expression by inhibiting NF-κB activation via the IKK/IκB signaling cascade. Verproside has potent anti-inflammatory, antioxidant, antinociceptive activities and ir is a potent anti-asthmatic/COPD drug candidate in vivo[1]. NF-κB TNF-α IKK
Verproside (2.5-20 μM; for 2 hours) markedly reduces phosphorylation levels of IKKα/β, IκBα, and TAK1 in the 5-20 μM range[1]. Western Blot Analysis[1] Cell Line: NCI-H292 cells
Verproside (Intragastrically; 30 mg/kg; 48 hours) significantly reduces the immunoglobulin E (IgE) levels of verproside-treated mice[2]. Animal Model: Specific pathogen-free female BALB/c mice aged 8-10 weeks[2]
[1]. Lee SU, et al. Verproside inhibits TNF-α-induced MUC5AC expression through suppression of the TNF-α/NF-κB pathway in human airway epithelial cells. Cytokine. 2016 Jan;77:168-75. [2]. Oh SR, et al. Suppressive effect of verproside isolated from Pseudolysimachion longifolium on airway inflammation in a mouse model of allergic asthma. Int Immunopharmacol. 2006 Jun;6(6):978-86. Epub 2006 Feb 10.
| Cas No. | 50932-20-2 | SDF | |
| 别名 | 毛蕊花糖苷 | ||
| Canonical SMILES | OC1=C(O)C=CC(C(O[C@@H]2[C@H]3[C@@](O3)(CO)[C@@]([C@@]2([H])C=CO4)([H])[C@@H]4O[C@]5([H])O[C@H](CO)[C@@H](O)[C@H](O)[C@H]5O)=O)=C1 | ||
| 分子式 | C22H26O13 | 分子量 | 498.43 |
| 溶解度 | Soluble in DMSO | 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 | 2.0063 mL | 10.0315 mL | 20.063 mL |
| 5 mM | 0.4013 mL | 2.0063 mL | 4.0126 mL |
| 10 mM | 0.2006 mL | 1.0031 mL | 2.0063 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。
In vitro and in vivo metabolism of Verproside in rats
Molecules 2012 Oct 12;17(10):11990-2002.PMID:23085650DOI:10.3390/molecules171011990.
Verproside, a catalpol derivative iridoid glycoside isolated from Pseudolysimachion rotundum var. subintegrum, is a biologically active compound with anti-inflammatory, antinociceptic, antioxidant, and anti-asthmatic properties. Twenty-one metabolites were identified in bile and urine samples obtained after intravenous administration of Verproside in rats using liquid chromatography-quadrupole Orbitrap mass spectrometry. Verproside was metabolized by O-methylation, glucuronidation, sulfation, and hydrolysis to Verproside glucuronides (M1 and M2), Verproside sulfates (M3 and M4), picroside II (M5), M5 glucuronide (M7), M5 sulfate (M9), isovanilloylcatalpol (M6), M6 glucuronide (M8), M6 sulfate (M10), 3,4-dihydroxybenzoic acid (M11), M11 glucuronide (M12), M11 sulfates (M13 and M14), 3-methyoxy-4-hydroxybenzoic acid (M15), M15 glucuronides (M17 and M18), M15 sulfate (M20), 3-hydroxy-4-methoxybenzoic acid (M16), M16 glucuronide (M19), and M16 sulfate (M21). Incubation of Verproside with rat hepatocytes resulted in thirteen metabolites (M1-M11, M13, and M14). Verproside sulfate, M4 was a major metabolite in rat hepatocytes. After intravenous administration of Verproside, the drug was recovered in bile (0.77% of dose) and urine (4.48% of dose), and O-methylation of Verproside to picroside II (M5) and isovanilloylcatalpol (M6) followed by glucuronidation and sulfation was identified as major metabolic pathways compared to glucuronidation and sulfation of Verproside in rats.
Verproside inhibits TNF-α-induced MUC5AC expression through suppression of the TNF-α/NF-κB pathway in human airway epithelial cells
Cytokine 2016 Jan;77:168-75.PMID:26318254DOI:10.1016/j.cyto.2015.08.262.
Airway mucus secretion is an essential innate immune response for host protection. However, overproduction and hypersecretion of mucus, mainly composed of MUC5AC, are significant risk factors in asthma and chronic obstructive pulmonary disease (COPD) patients. Previously, we reported that Verproside, a catalpol derivative iridoid glycoside isolated from Pseudolysimachion rotundum var. subintegrum, is a potent anti-asthmatic candidate drug in vivo. However, the molecular mechanisms underlying the pharmacological actions of Verproside remain unknown. Here, we found that Verproside significantly reduces the expression levels of tumor necrosis factor alpha (TNF-α)-induced MUC5AC mRNA and protein by inhibiting both nuclear factor kappa B (NF-κB) transcriptional activity and the phosphorylation of its upstream effectors such as IκB kinase (IKK)β, IκBα, and TGF-β-activated kinase 1 (TAK1) in NCI-H292 cells. Moreover, Verproside attenuated TNF-α-induced MUC5AC transcription more effectively when combined with an IKK (BAY11-7082) or a TAK1 (5z-7-oxozeaenol) inhibitor than when administered alone. Importantly, we demonstrated that Verproside negatively modulates the formation of the TNF-α-receptor (TNFR) 1 signaling complex [TNF-RSC; TNFR1-recruited TNFR1-associated death domain protein (TRADD), TNFR-associated factor 2 (TRAF2), receptor-interacting protein kinase 1 (RIP1), and TAK1], the most upstream signaling factor of NF-κB signaling. In silico molecular docking studies show that Verproside binds between TRADD and TRAF2 subunits. Altogether, these results suggest that Verproside could be a good therapeutic candidate for treatment of inflammatory airway diseases such as asthma and COPD by blocking the TNF-α/NF-κB signaling pathway.
Pharmacokinetics of Verproside after intravenous and oral administration in rats
Arch Pharm Res 2009 Apr;32(4):559-64.PMID:19407974DOI:10.1007/s12272-009-1412-x.
Verproside, a catalpol derivative iridoid glucoside isolated from Pseudolysimachion longifolium, is a candidate for anti-asthmatic drug. The dose-dependency of the pharmacokinetics of Verproside was evaluated in rats after intravenous and oral administration. After intravenous administration of Verproside (2, 5 and 10 mg/kg doses), the systemic clearance (Cl) was significantly reduced and AUC was significantly increased at 10 mg/kg dose compared to 2 and 5 mg/kg doses. The volume of distribution at steady state (V (ss)) remained unchanged as the dose was increased. The extent of urinary excretion was low for both intravenous (3.3-6.2%) and oral (0.01-0.04%) doses. Isovanilloylcatalpol was identified as a metabolite after intravenous administration of Verproside and showed the significant decreases in AUC and C (max) at 10 mg/kg Verproside dose. The reduced systemic clearance of Verproside at high doses appears to be due to the saturable metabolism. Upon oral administration of Verproside (20, 50 and 100 mg/kg doses), C (max) was nonlinearly increased. The extent of Verproside recovered from the gastrointestinal tract at 24 h after oral administration was 0.01-0.72% for all three doses studied. The absolute oral bioavailability (F) was 0.3 and 0.5% for 50 and 100 mg/kg doses, respectively. Low F appears to be due to first-pass metabolism.
Multiple UDP-Glucuronosyltransferase and Sulfotransferase Enzymes are Responsible for the Metabolism of Verproside in Human Liver Preparations
Molecules 2017 Apr 22;22(4):670.PMID:28441724DOI:10.3390/molecules22040670.
Verproside, an active iridoid glycoside component of Veronica species, such as Pseudolysimachion rotundum var. subintegrum and Veronica anagallis-aquatica, possesses anti-asthma, anti-inflammatory, anti-nociceptive, antioxidant, and cytostatic activities. Verproside is metabolized into nine metabolites in human hepatocytes: Verproside glucuronides (M1, M2) via glucuronidation, Verproside sulfate (M3) via sulfation, picroside II (M4) and isovanilloylcatalpol (M5) via O-methylation, M4 glucuronide (M6) and M4 sulfate (M8) via further glucuronidation and sulfation of M4, and M5 glucuronide (M7) and M5 sulfate (M9) via further glucuronidation and sulfation of M5. Drug-metabolizing enzymes responsible for Verproside metabolism, including sulfotransferase (SULT) and UDP-glucuronosyltransferase (UGT), were characterized. The formation of Verproside glucuronides (M1, M2), isovanilloylcatalpol glucuronide (M7), and picroside II glucuronide (M6) was catalyzed by commonly expressed UGT1A1 and UGT1A9 and gastrointestinal-specific UGT1A7, UGT1A8, and UGT1A10, consistent with the higher intrinsic clearance values for the formation of M1, M2, M6, and M7 in human intestinal microsomes compared with those in liver microsomes. The formation of Verproside sulfate (M3) and M5 sulfate (M9) from Verproside and isovanilloylcatalpol (M5), respectively, was catalyzed by SULT1A1. Metabolism of picroside II (M4) into M4 sulfate (M8) was catalyzed by SULT1A1, SULT1E1, SULT1A2, SULT1A3, and SULT1C4. Based on these results, the pharmacokinetics of Verproside may be affected by the co-administration of relevant UGT and SULT inhibitors or inducers.
Suppressive effect of Verproside isolated from Pseudolysimachion longifolium on airway inflammation in a mouse model of allergic asthma
Int Immunopharmacol 2006 Jun;6(6):978-86.PMID:16644484DOI:10.1016/j.intimp.2006.01.010.
Allergic inflammation of the airways has a critical role in asthma development. We investigated a suppressive effect of Verproside (3,4-dihydroxy catalpol) isolated from the extract of Pseudolysimachion longifolium on asthmatic parameters--such as immunoglobulin E (IgE) level, cytokine release, eosinophilia, airway hyperresponsiveness and mucus hypersecretion--in an OVA-sensitized/challenged mouse model. Verproside significantly inhibited the increase of total IgE and the cytokines IL-4 and IL-13 in plasma and bronchoalveolar lavage fluid, and also effectively suppressed airway hyperresponsiveness, eosinophilia and mucus hypersecretion in OVA-induced asthmatic mice. The efficacy of Verproside was comparable to montelukast, an anti-asthmatic drug that is currently available. These results suggest that Verproside could be a major marker in herbal medicines that are used for asthma treatment, and could also act as a lead for anti-asthmatic drugs.