Agnuside
(Synonyms: 穗花牡荆苷; Agnoside) 目录号 : GC40750
An iridoid glycoside with diverse biological activities
Cas No.:11027-63-7
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
Agnuside is an iridoid glycoside originally isolated from V. rotundifolia fruit that has diverse biological activities. It inhibits COX-2 with an IC50 value of 0.026 mg/ml but exhibits less than 10% inhibition of COX-1 at this concentration. It also inhibits 46.3, 66.8, and 82.1% of P-glycoprotein (P-gp) ATPase activity at concentrations of 5, 25, and 100 μM, respectively. Agnuside (0.1-10 μM) induces proliferation of MCF-7 breast cancer cells, an effect that is inhibited by the estrogen receptor antagonist fulvestrant . In vivo, agnuside (50 mg/kg) reduces acetic acid-induced writhing in mice indicating analgesia. It also suppresses production of the pro-inflammatory mediators prostaglandin E2 (PGE2) and leukotriene B4 and the T cell-mediated cytokines IL-2, TNF-α, INF-γ, IL-4, IL-10, and IL-17 in splenocytes and arthritic paw tissue from arthritic adrenalectomized rats.
| Cas No. | 11027-63-7 | SDF | |
| 别名 | 穗花牡荆苷; Agnoside | ||
| Canonical SMILES | OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@](O[C@H]2[C@@](C(COC(C3=CC=C(O)C=C3)=O)=C[C@H]4O)([H])[C@@]4([H])C=CO2)([H])O1 | ||
| 分子式 | C22H26O11 | 分子量 | 466.4 |
| 溶解度 | DMF: 10 mg/ml,DMSO: 10 mg/ml,Ethanol: 0.5 mg/ml,PBS (pH 7.2): 0.2 mg/ml | 储存条件 | 4°C, protect from 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 | 2.1441 mL | 10.7204 mL | 21.4408 mL |
| 5 mM | 0.4288 mL | 2.1441 mL | 4.2882 mL |
| 10 mM | 0.2144 mL | 1.072 mL | 2.1441 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。
Agnuside Alleviates Synovitis and Fibrosis in Knee Osteoarthritis through the Inhibition of HIF-1 α and NLRP3 Inflammasome
Mediators Inflamm 2021 Mar 16;2021:5534614.PMID:33814979DOI:10.1155/2021/5534614.
Increasing evidence has shown that NLRP3 inflammasome activation participates in chronic aseptic inflammation and is related to tissue fibrosis. Our last study also revealed the vital role of NLRP3 inflammasome, highly associated with tissue hypoxia, in the onset and development of knee osteoarthritis (KOA). In this study, we tried to find a possible benign intervention for that pathological process. Agnuside (AGN), a nontoxic, natural small molecule isolated from the extract of Vitex negundo L. (Verbenaceae), has been demonstrated to have antioxidation, anti-inflammatory, analgesia, and many other properties as an iridoid glycoside, although its specific target is still unclear. Therefore, we established MIA-induced KOA model rats and investigated the effects of AGN oral gavage on oxygen-containing state, NLRP3 inflammasome, synovitis, and fibrosis in KOA. Pimonidazole staining and HIF-1α immunohistochemical assay both showed that AGN at the oral dose of 6.25 mg/kg can effectively relieve local hypoxia in synovial tissue. Besides, we observed a decrease of HIF-1α, caspase-1, ASC, and NLRP3 after AGN intervention, both in the mRNA and protein levels. In addition, rats treated with the AGN showed less inflammatory reaction and fibrosis, not only in the expression of NLRP3, inflammasome downstream factors IL-1β and IL-18, and fibrosis markers TGF-β, TIMP1, and VEGF but also in the observation of HE staining, anatomical characteristics, Sirius Red staining, and type I collagen immunohistochemistry. Subsequently, we established LPS-induced models of fibroblast-like synoviocytes (FLSs) mimicking the inflammatory environment of KOA and activating NLRP3 inflammasome. FLSs treated with AGN (3 μM) resulted in a downregulation of HIF-1α and the components required for NLRP3 inflammasome activation. Meanwhile, the content of proinflammatory factors IL-1β and IL-18 in FLS supernatant was also reduced by AGN. In addition, both mRNA and protein levels of the fibrotic markers were significantly decreased after AGN management. To conclude, this study demonstrates that AGN alleviates synovitis and fibrosis in experimental KOA through the inhibition of HIF-1α accumulation and NLRP3 inflammasome activation. Additionally, not only does it reveal some novel targets for anti-inflammatory and antioxidant effects of AGN but also announces its potential value in treating KOA in humans.
Agnuside mitigates OVA-LPS induced perturbed lung homeostasis via modulating inflammatory, autophagy, apoptosis-fibrosis response and myeloid lineages in mice model of allergic asthma
Int Immunopharmacol 2022 May;106:108579.PMID:35144202DOI:10.1016/j.intimp.2022.108579.
Attributes of Agnuside, a nontoxic, iridoid glycoside have been advocated for inflammatory disorders. However, information on its efficacy in alleviating allergic asthma largely remain ambiguous and yet to be deciphered. Present study aimed to assess efficacy of Agnuside in targeting vicious circle of oxi-inflammation, autophagy and fibrosis, together with investigating its underlying molecular mechanism during OVA-LPS induced allergic asthma. Results revealed that Agnuside showed prophylactic effect in assuaging asthmatic lung architecture impairment (p ≤ 0.01) as indicated by suppression of inflammatory cell infiltration, congestion, fibrosis, airway remodeling and alveolar collapse in OVA-LPS sensitized group. Decreased expression level (p ≤ 0.05) of allergic inflammatory mediators such as IgE, Th1/Th2, IL-4/IFN-γ, IL-4/IL-10, chemokines, endopeptidases and TGF-β, Smad2/4, Caspase9/3, connexin 43/50 observed in Agnuside treatments. Analysis of redox molecular signaling cascade and autophagic proteins revealed concurrent upregulation in p-NF-κB, p-PI3K, p-Akt, p-p38, p-Stat3 activation, GATA3, LC3B expression and reduction in Bcl2/Bax, Beclin1 and p62 expression in sensitized mice (p ≤ 0.05) which were intensely counteracted by administration of Agnuside. Suppression in myeloid cells activation and augmentation (p ≤ 0.001) of Tregs established modulatory attribute of Agnuside for innate and adaptive immune response during allergic asthma. Collectively, these outcomes confer prophylactic attribute of Agnuside and signify it as promising strategy to thwart allergic asthma.
Identification and characterization of Agnuside, a natural proangiogenic small molecule
Eur J Med Chem 2018 Dec 5;160:193-206.PMID:30340142DOI:10.1016/j.ejmech.2018.10.009.
Due to its important role in regulating angiogenesis, vascular homeostasis and remodeling, and arteriogenesis in blood vascular and lymphatic endothelial cells, VEGFR2 stimulation has demonstrated promise in preclinical studies as an endovascular treatment for ischemic myocardial and peripheral disease. However, the short half-life of protein- and cytokine-based strategies and transduction inefficiency of vector-based modalities have hindered its clinical therapeutic applications. In the present study, we used a streamlined bioinformatics strategy combining ligand-based pharmacophore development and validation, virtual screening, and molecular docking to identify Agnuside, a non-toxic, natural small molecule extract of Vitex agnus-castus possessing strong binding affinity, druggable physiochemical properties, and conformationally stable hydrogen bond and hydrophobic interactions with catalytically important residues within VEGFR2's active and allosteric sites. In-vitro proliferation, tube formation, and scratch wound migration assays provide evidence that Agnuside promotes endothelial cell angiogenesis. Agnuside increases HUVEC proliferation with an EC50 of 1.376 μg/mL, stimulates tubulogenesis dose-dependently, and increases scratch wound migration rate. An additional angiogenesis assay suggests that Agnuside may actively compete with a VEGFR2 inhibitor for VEGFR2 binding site occupancy to increase total length and branching length of HUVEC tubular networks. Chemometric analysis of molecular interaction fields (MIFs) by partial least squares (PLS)-derived quantitative structure activity relationship (QSAR) analysis and MIF contours provides the framework for the formulation of Agnuside analogues possessing greater potency. Our research supports that Agnuside may be a lead molecule for therapeutic angiogenesis.
Anti-arthritic activity of Agnuside mediated through the down-regulation of inflammatory mediators and cytokines
Inflamm Res 2012 Apr;61(4):293-304.PMID:22228102DOI:10.1007/s00011-011-0410-x.
Objective and design: The purpose of this study was to elucidate the probable mechanism for the anti-arthritic activity of Agnuside (AGN), a compound isolated from the leaf extract of Vitex negundo. Methodology: The anti-inflammatory activity of AGN within a dose range of 1.56-12.50 mg/kg in normal and adrenalectomized rats was evaluated against different inflammagens. An array of pro-inflammatory mediators (PGE(2) and LTB(4)) and T-cell-mediated cytokines (IL-2, TNF-α, IFN-γ, IL-4, IL-10, IL-17) was assayed using flow cytometry, in arthritic paw tissue homogenate and splenocytes of treated animals. Results: Significant anti-arthritic activity was observed in the polyarthritis test in rats and this was associated with significant suppression of inflammatory mediators and T-cell-mediated cytokines (Th1/Th2). The anti-inflammatory activity in adrenalectomized rats confirmed that the effect of AGN is not mediated by the pituitary-adrenal axis. AGN also showed inhibition of vascular permeability and leukocyte migration in vivo. Conclusion: The study suggests the possible development of AGN as a therapeutic agent in the treatment of arthritis by the modulation of the host immune response.
Plasma pharmacokinetics, bioavailability and tissue distribution of Agnuside following peroral and intravenous administration in mice using liquid chromatography tandem mass spectrometry
J Pharm Biomed Anal 2016 Jun 5;125:154-64.PMID:27018507DOI:10.1016/j.jpba.2016.02.047.
Agnuside (AGN), an iridoid glycoside, is the chemotaxonomic marker of the genus Vitex which has gained enormous attention by virtue of its potential health benefits. Regardless of claiming many therapeutic applications reports demonstrating its pharmacokinetics or quantification in biomatrices are lacking. This is the first report which presents a sensitive liquid chromatography coupled to a tandem mass spectrometry (LC-MS/MS) method for the quantification of AGN in mice plasma and various tissues (including liver, intestine, spleen, kidney, heart, lungs and brain). AGN was extracted from the biological samples using protein precipitation followed by liquid-liquid extraction and the separation was achieved on C18 reversed phase column with a mobile phase consisted of 0.1% formic acid in acetonitrile-0.1% formic acid in triple distilled water (92:8, v/v) at a flow rate of 0.7mL/min. The MS/MS detection was performed by electrospray ionization (ESI) using multiple reaction monitoring (MRM) in negative scan mode. The bioanalytical method was found linear over the concentration range of 1-4000ng/mL for plasma and tissue homogenates (r(2)≥0.990). The lower limit of quantitation (LLOQ) for all matrices was 1ng/mL. Intra-day and inter-day variance and accuracy ranged from 90 to 110% and 1-10%, respectively. Matrix effect and recoveries were well within the satisfactory limits. The validated method was applied successfully to measure AGN concentrations in plasma and tissues following intravenous (i.v.) and peroral (p.o.) administration to mice. Maximal AGN concentrations in plasma and tissues were reached within 30-45min. The mean absolute bioavailability (%F) of AGN was∼0.7%. After oral administration, AGN was most abundant in intestine, followed by kidney, liver, spleen, brain, lungs and heart. The identified target tissues of AGN may help in understanding its pharmacological action in vivo.