Doxofylline 是一种口服有效的PDE IV抑制剂，也是A1AR拮抗剂。Doxofylline 通过抑制线粒体 ROS 的产生，以及改善多种细胞途径 (包括NLRP3-TXNIP炎症体的激活) 来减轻上皮细胞的炎症。Doxophylline 可用于哮喘、慢性阻塞性肺病和支气管痉挛的研究。
| 生物活性 | Doxofylline is an orally activePDE IVinhibitor andA1ARantagonist. Doxofylline reduces inflammation in epithelial cells via inhibiting mitochondrial ROS production and amelioration of multiple cellular pathways (NLRP3-TXNIPinflammasome activation). Doxophylline can be used in studies of asthma, chronic obstructive pulmonary disease, and bronchospasm[1][2][3]. |
| IC50& Target | Adenosine A1 receptor, phosphodiesterase IV[1][2][3]. |
体外研究
(In Vitro) | Doxofylline (5, 10 μM; 48 h) shows potent protection against LPS-induced epithelial inflammation by reducing PGE2, NO release, and decreasing mitochondrial ROS generation in 16HBE cells[1].
Doxofylline (5, 10 μM; 48 h) suppresses LPS-induced expression of NADPH oxidase subunits and TXNIP 16HBE cells[1].
Doxofylline (5, 10 μM; 48 h) inhibits LPS-induced NLRP3 inflammasome activation and secretion of IL-1b and IL-18, as well as mitigates LPS-mediated SIRT1 reduction[1].
Doxofylline (0.1-10 μM; 15 min) significantly reduces fMLP-induced leukocyte migration in BM cells (fMLP: Formyl-Methionyl-Leucyl-Phenylalanine)[2].
Cell Viability Assay[1] | Cell Line: | 16HBE cells | | Concentration: | 5, 10 μM | | Incubation Time: | 48 h | | Result: | Weakened LPS-induced NO and PGE2in a dose-dependent manner.
Exerted dose-dependent inhibition on LPS-induced mitochondrial ROS production and NADPH oxidase subunits expression.
Suppressed LPS-induced TXNIP expression and NLRP3 inflammasome activation at the protein level in a dose-dependent manner.
Inhibited LPS-induced secretion of IL-1b and IL-18. |
Cell Viability Assay[2] | Cell Line: | BM cells (from naive mice) | | Concentration: | 0.1-10 μM | | Incubation Time: | 15 min (pretreat) | | Result: | Notably surpressed positive migration of BM cells in response to fMLP. |
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体内研究
(In Vivo) | Doxofylline (0.3, 1 mg/kg; i.p.; single) inhibits LPS-induced inflammation in the lungs of mice[2].
Doxofylline (0.3 mg/kg; i.p.; pre-treat; single) notably reduces the adhesion of cells to the vascular tissue and surpresses the expression of LPS-induced ICAM-1 in vivo[2].
| Animal Model: | Male BALB/c mice (6 to 8-week-old)[2]. | | Dosage: | 0.3, 1 mg/kg | | Administration: | Intraperitoneal injection; single. | | Result: | Significantly inhibited the migration of neutrophils and the release of IL-6 and TNF-a into the lung lumen.
Increased the bone marrow leukocyte numbers to levels similar to those seen in the saline-treated group.
Notably reduced the number of circulating leukocytes in comparison to LPS-treated mice.
Significantly reduced accumulation of neutrophils in the peribronchial area. |
| Animal Model: | Male BALB/c mice (6 to 8-week-old)[2]. | | Dosage: | 0.3 mg/kg | | Administration: | Intraperitoneal injection; pre-treat; single. | | Result: | Significantly reduced the adhesion of cells to the vascular tissue, but not the rolling of cells along the vessel wall in mice.
Significantly reduced the expression of ICAM-1 induced by LPS. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 50 mg/mL(187.79 mM;Need ultrasonic) H2O : 25 mg/mL(93.90 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.7559 mL | 18.7793 mL | 37.5587 mL | | 5 mM | 0.7512 mL | 3.7559 mL | 7.5117 mL | | 10 mM | 0.3756 mL | 1.8779 mL | 3.7559 mL |
*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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： PBS Solubility: 65 mg/mL (244.13 mM); Clear solution; Need ultrasonic and warming and heat to 60℃ 2. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (9.39 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (9.39 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 3. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (9.39 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (9.39 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 4. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (9.39 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (9.39 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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