Isosinensetin
(Synonyms: 异橙黄酮) 目录号 : GC36345
A polymethoxylated flavone with anticancer and anti-inflammatory activities
Cas No.:17290-70-9
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
Isosinensetin is a polymethoxylated flavone that has been found in C. reticulata and has anticancer and anti-inflammatory activities.1,2,3 It inhibits P-glycoprotein (P-gp; IC50 = 4.2 ?M) and increases the cytotoxicity of paraquat in MDR1-MDCKII cells and paclitaxel in MX-1 breast and paclitaxel-resistant MX-1/T cancer cells.1 Isosinensetin inhibits the proliferation of A549 lung, HL-60 leukemia, MCF-7 breast, and HO-8910 ovarian cancer cells (IC50s = 23.6, 23.8, 15.1, and 12.5 ?M, respectively).2 It prevents decreases in cell viability and inhibits increases in IL-1β, TNF-α, and IL-6 levels and the production of reactive oxygen species (ROS) induced by fine particulate matter less than or equal to 2.5 ?m (PM2.5) in 16HBE bronchial epithelial cells when used at a concentration of 80 ?g/ml.3
1.Bai, J., Zhao, S., Fan, X., et al.Inhibitory effects of flavonoids on P-glycoprotein in vitro and in vivo: Food/herb-drug interactions and structure-activity relationshipsToxicol. Appl. Pharmacol.36949-59(2019) 2.Du, Q., and Chen, H.The methoxyflavones in Citrus reticulata Blanco cv. ponkan and their antiproliferative activity against cancer cellsFood Chem.119(2)567-572(2010) 3.Zou, Y., Li, S., Li, X., et al.Isosinensetin alleviates the injury of human bronchial epithelial cells induced by PM2.5Exp. Ther. Med.22(6)1435(2021)
| Cas No. | 17290-70-9 | SDF | |
| 别名 | 异橙黄酮 | ||
| Canonical SMILES | O=C1C=C(C2=CC=C(OC)C(OC)=C2)OC3=C(OC)C(OC)=CC(OC)=C13 | ||
| 分子式 | C20H20O7 | 分子量 | 372.37 |
| 溶解度 | DMSO : 12.5 mg/mL (33.57 mM; Need ultrasonic) | 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 | 2.6855 mL | 13.4275 mL | 26.855 mL |
| 5 mM | 0.5371 mL | 2.6855 mL | 5.371 mL |
| 10 mM | 0.2686 mL | 1.3428 mL | 2.6855 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。
Isosinensetin alleviates the injury of human bronchial epithelial cells induced by PM2.5
Exp Ther Med 2021 Dec;22(6):1435.PMID:34707716DOI:10.3892/etm.2021.10870.
Flavonoids which are extracted from citrus peel and pulp have been reported to have multiple beneficial effects on human health. Isosinensetin (ISO) is a type of flavonoid compound, which has several protective effects including anticancer, antioxidant, antiviral, anti-inflammatory and bacteriostatic. However, the molecular mechanism of its antioxidant and anti-inflammatory effects remain unclear. The present study aimed to investigate the intervention effect and possible mechanism of ISO on human bronchial epithelial cells injured by fine particular matter ≤2.5 µm in diameter (PM2.5). In the present study, the cell viability was detected by Cell Counting Kit-8 method. The levels of pro-inflammatory cytokines were analyzed by ELISA. The level of reactive oxygen species (ROS) was detected by fluorescence probe. The expression levels of proliferating cell nuclear antigen (PCNA), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor кΒ (NF-кB) proteins were detected by western blotting. The results revealed that ISO evidently increased the viability of 16-HBE cells and sharply decreased the levels of pro-inflammatory factors in cell culture supernatant. ISO significantly inhibited ROS release caused by PM2.5. Moreover, the expression levels of PCNA, Nrf2 and NF-кB proteins were downregulated after ISO incubation. These results indicated that ISO alleviated 16-HBE-cell injury by PM2.5 through the ROS-Nrf2/NF-кB signaling pathway.
Determination of Isosinensetin in rat plasma by UHPLC-MS/MS: Application to oral and intravenous pharmacokinetic study in healthy rats
J Pharm Biomed Anal 2020 May 30;184:113210.PMID:32126459DOI:10.1016/j.jpba.2020.113210.
Isosinensetin is a polymethoxyflavone existing in various kinds of citrus. It has exhibited significant anti-proliferative activity and herb-drug interaction. To date, a specific determination method to quantify Isosinensetin concentration in biological matrix has not been developed. In the present study, a highly specific, simple and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) approach was developed and validated for quantification of Isosinensetin in rat plasma with subsequent application to a pharmacokinetic study. Isosinensetin and lysionotin (internal standard, IS) were extracted from rat plasma by a single step protein precipitation using acetonitrile as precipitation agent. The chromatographic separation was conducted using an Agilent C18 column with a gradient elution system (0.1 % formic acid aqueous solution and acetonitrile) within 3.5 min. An electrospray ionization (ESI) source operating in positive mode and multiple reaction monitoring (MRM) were used to monitor the transitions of m/z 373.1 → 343.1 for Isosinensetin and m/z 345.1 → 315.1 for IS. The developed method was linear within the range of 1-1000 ng/mL and fully validated according to FDA guidelines. The accuracy values reported as relative errors were between 2.0 and 10.0 % for three quality control levels (2, 400 and 800 ng/mL) and lower limit of quantification (LLOQ). The precisions were ≤11.1 % for quality controls and ≤18.1 % for LLOQ. The recoveries and matrix effects of Isosinensetin were in the range of 83.4-87.7 % and 105.6-108.8 %, respectively. Other parameters such as selectivity, carryover effect, dilution integrity and stability were also validated and met the acceptance criteria. The method was applied to a pharmacokinetic study in rats following oral and intravenous administration of Isosinensetin. Isosinensetin was rapidly absorbed with a poor bioavailability of 2.19 % and quickly eliminated with mean half-life of 1.40 h and 1.76 h for oral and intravenous route, respectively.
Isosinensetin alleviates estrogen deficiency-induced osteoporosis via suppressing ROS-mediated NF-κB/MAPK signaling pathways
Biomed Pharmacother 2023 Apr;160:114347.PMID:36746095DOI:10.1016/j.biopha.2023.114347.
The formation of osteoclasts and their hyperactive bone resorption are related to the aggregation of intracellular reactive oxygen species (ROS). Flavonoids, derived from plant active ingredients, can alleviate the symptoms of osteoporosis (OP). Isosinensetin (Iss) is a flavonoid with antioxidant effects obtained mainly from citrus fruits, and its effect on osteoclastogenesis has not been reported. In this study, we investigated the antioxidant activity of Iss on osteoclast differentiation and function, as well as the therapeutic impact of Iss on OP. We found that Iss inhibited osteoclastogenesis and suppressed the bone resorption function of osteoclasts. Additionally, Iss reduced receptor activator of nuclear factor-κB ligand (RANKL)-induced intracellular ROS. Using quantitative real-time polymerase chain reaction and western blot, we further found that Iss inhibited osteoclast-specific genes and related proteins, while promoting the expression of antioxidant enzyme-related genes and proteins. Mechanistically, Iss reduces intracellular ROS by activating nuclear factor-erythroid 2-related factor 2 (Nrf2) and its related antioxidant enzymes and inhibits the downstream nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways of ROS, which in turn inhibits nuclear factor of activated T cells 1 (NFATc1), and ultimately inhibits osteoclastogenesis. In vivo, by micro-computed tomography (Micro-CT) assay and histological analyses, we found that Iss could reduce bone loss in ovariectomized (OVX) mice. Therefore, Iss has the potential as an OP preventative and therapeutic drug option.
Isosinensetin Stimulates Glucagon-like Peptide-1 Secretion via Activation of hTAS2R50 and the Gβγ-Mediated Signaling Pathway
Int J Mol Sci 2023 Feb 12;24(4):3682.PMID:36835092DOI:10.3390/ijms24043682.
Bitter taste receptors (TAS2Rs) are G protein-coupled receptors localized in the taste buds of the tongue. They may also be present in non-lingual organs, including the brain, lung, kidney, and gastrointestinal (GI) tract. Recent studies on bitter taste receptor functions have suggested TAS2Rs as potential therapeutic targets. The human bitter taste receptor subtype hTAS2R50 responds to its agonist Isosinensetin (ISS). Here, we demonstrated that, unlike other TAS2R agonists, Isosinensetin activated hTAS2R50 as well as increased Glucagon-like peptide 1 (GLP-1) secretion through the Gβγ-mediated pathway in NCI-H716 cells. To confirm this mechanism, we showed that ISS increased intracellular Ca2+ and was suppressed by the IP3R inhibitor 2-APB as well as the PLC inhibitor U73122, suggesting that TAS2Rs alters the physiological state of enteroendocrine L cells in a PLC-dependent manner. Furthermore, we demonstrated that ISS upregulated proglucagon mRNA and stimulated GLP-1 secretion. ISS-mediated GLP-1 secretion was suppressed in response to small interfering RNA-mediated silencing of Gα-gust and hTAS2R50 as well as 2-APB and U73122. Our findings improved the understanding of how ISS modulates GLP-1 secretion and indicates the possibility of using ISS as a therapeutic agent in the treatment of diabetes mellitus.
Identification of the active compounds and functional mechanisms of Jinshui Huanxian formula in pulmonary fibrosis by integrating serum pharmacochemistry with network pharmacology
Phytomedicine 2022 Jul 20;102:154177.PMID:35636171DOI:10.1016/j.phymed.2022.154177.
Background: Jinshui Huanxian formula (JHF), a traditional Chinese medicine (TCM), has been demonstrated to attenuate idiopathic pulmonary fibrosis (IPF). The active compounds and underlying mechanisms of JHF, however, are unclear. Purpose: The purpose of This study was to aimed to identify the active compounds and pharmacological mechanism of JHF by integrating serum pharmacochemistry with a network pharmacology strategy. Methods: JHF was orally administered to a rat model with bleomycin (BLM)-induced pulmonary fibrosis (PF). The pharmacodynamic effects and compounds present in the serum were identified. The targets and biological mechanisms of these compounds were revealed using network analysis and validated using in vitro experiments. Results: JHF could significantly ameliorate BLM-induced PF by preventing extracellular matrix collagen deposition. Twenty-seven compounds that were found to be enriched in the serum samples collected 1 h after oral administration with JHF were identified as the candidate active compounds, and their 423 potential targets were identified as JHF targets. primarily related to the advanced glycation and products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway, phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB or AKT) signaling pathway, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, etc. The 423 targets, 1145 IPF-related genes and their overlapped genes were applied to analyze, respectively. The results showed that these genes were primarily related to the advanced glycation end-products-receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, lipid and atherosclerosis pathology, phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB or AKT) signaling pathway, and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance. Furthermore, the affinity between serum JHF compounds and the main proteins in the above important pathways was investigated through molecular docking. As a result, Molecular docking analysis showed that, tangeretin, Isosinensetin, and peimine were found to could bind to EGFR and AKT, and their inhibitory effect on EGFR and AKT were validated in fibroblast cell induced by transforming growth factor (TGF)TGF-β. The results indicated that suppression of fibroblast activation by inhibiting the EGFR/PI3K/AKT signaling pathway might be an important mechanism of JHF may to treat PF. Conclusion: JHF may suppress fibroblast activation by inhibiting the EGFR/PI3K/AKT signaling pathway to ameliorate PF. Tangeretin, Isosinensetin, and peimine may be the active compounds in JHF involved in the treatment of that have therapeutic effects on IPF.