Methylophiopogonanone A
(Synonyms: 麦冬高异黄酮A) 目录号 : GN10454
甲基麦冬酮 A (MOA) 是一种从草药麦冬中分离出来的具有丰富生物活性的同型异黄酮，被认为是麦冬相关草药制剂质量控制的关键化学指标。
Cas No.:74805-92-8
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
| Cell experiment [1]: | |
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Cell lines |
Mouse brain endothelial bEND.3 cells, Human monocytic THP-1 cells |
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Preparation Method |
Cells were seeded at 5×105 cells per well on 24 well plates. After 12 hours, cells were incubated in a hypoxia chamber with Dulbecco＊s modified Eagle＊s medium (no glucose) supplemented with 10% (v/v) fetal bovine serum at 37～C in a 5% (v/v) CO2/ 95% (v/v) N2 for 12 hours, and then incubated under normal conditions at 37～C for another 24 hours. Before hypoxia, cells were treated with Methylophiopogonanone A (2.5, 5.0 or 10 uM), and control cells were cultured under normal conditions with vehicle. After stimulation, cells were lysated with an ultrasonic lysis instrument, and supernatants were collected for ICAM-1 and VCAM-1 ELISA detection. Human monocytic THP-1 cells were cultured in RPMI 1640 medium supplemented with 10% (v/v) fetal bovine serum at 37～C in a humidified atmosphere of 5% (v/v) CO2. Cells were seeded at 5×105 cells per well on 24 well plates, and stimulated with PMA (200 nM) or PMA (200 nM) + Methylophiopogonanone A (2.5, 5.0 or 10 uM) for 24 hours. After stimulation, cell culture supernatants were collected for MMP-9 ELISA detection, the MMP-9 ELISA was performed according to the protocols of human MMP-9 quantikine ELISA kit. |
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Reaction Conditions |
2.5, 5.0 or 10 µM for 24 hours |
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Applications |
The level of ICAM-1 and VCAM-1 were significantly enhanced in OGD/R-induced bEnd.3 cells (model group) when compared with the control group. MO-A treatment significantly inhibited the increase of ICAM-1 and VCAM-1 induced by OGD/R-treatment. |
| Animal experiment [1]: | |
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Animal models |
Sprague-Dawley rats |
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Preparation Method |
Middle cerebral artery occlusion (MCAO) was induced using the intraluminal suture method. To evaluate the neuroprotective effect of Methylophiopogonanone A (dissolved in normal saline with PH = 8.0), except for sham operation rats (Control), MCAO rats were randomly divided into 4 groups: MCAO with vehicle (model), and MCAO treated with 1.25, 2.50 or 5.00 mg/kg Methylophiopogonanone A twice per day. After 2 h reperfusion, the rats were treated intravenously with Methylophiopogonanone A for 7 days. Control rats were treated with equal volumes of saline. |
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Dosage form |
1.25, 2.50 or 5.00 mg/kg Methylophiopogonanone A twice per day for 7 days |
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Applications |
The infarct area of each treatment group was observed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Infarct volume was analyzed, and the results showed that there was no infarct in sham animals, but significant ischemic injury following transient MCAO (model group). TTC staining revealed that MO-A (2.5 mg/kg, 5.0 mg/kg) significantly reduced infarct volume when compared with the model group. |
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References: [1]: Lin M, Sun W, Gong W, et al. Methylophiopogonanone a protects against cerebral ischemia/reperfusion injury and attenuates blood-brain barrier disruption in vitro[J]. PLoS One, 2015, 10(4): e0124558. |
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Methylophiopogonanone A (MOA), an abundantly bioactive homoisoflavonoid isolated from the herbal medicine Ophiopogonis Radix, has been considered as the key chemical index for the quality control of Ophiopogonis Radix related herbal formulations [1]. Methylophiopogonanone A inhibited hUGTs effect of 4-HN-335 O-glucuronidation with IC50 values ranged from 1.23 ± 0.09 μμ (for UGT1A1) to 8.30 ± 0.72 μμ (for UGT2B7) [2].
Modern pharmacological studies have demonstrated that Methylophiopogonanone A held a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, anti-tumour, anti-hyperlipidemia effects and the potentials for attenuating myocardial apoptosis and improving cerebral ischemia/reperfusion injury [3,4,5,6].
Methylophiopogonanone A dose-dependently inhibited hUGT1A1-catalysed NHPN-O-glucuronidation in HeLa-UGT1A1 cells, with the apparent IC50 value of 1.54 ± 0.17 μM [2]. Methylophiopogonanone A (2.5-10 μM) treatment significantly reversed the decreased TER values when compared with the model group, which indicated that Methylophiopogonanone A had a protective effect on hypoxic BBB damage [5]. In H9C2 cells subjected to H/R, pretreatment with Methylophiopogonanone A (10 μmol/L) significantly decreased apoptosis and cleaved caspase-3 expression, elevated the Bcl-2/Bax ratio and restored NO production [6].
Pretreatment with Methylophiopogonanone A (10 mg.kg-1.d-1, po.) significantly reduced the infarct size (by 60.7%) and myocardial apoptosis (by 56.8%), and improved cardiac function, in I/R mice [6]. Cerebral water contents were less in the Methylophiopogonanone A (2.5 mg/kg and 5.0 mg/kg) treatment groups than those in the model group in MCAO rats [5].
References:
[1]. Zheng Y, Fan C, Liu M, Chen Y, Lu Z, Xu N, Huang H, Zeng H, Liu S, Cao H, Liu J. Overall quality control of the chemical and bioactive consistency of ShengMai Formula. Journal of pharmaceutical and biomedical analysis. 2020 Sep 10;189:113411.
[2]. Zhou Q H, Zhu G H, Song Y Q, et al. Methylophiopogonanone A is a naturally occurring broad‐spectrum inhibitor against human UDP‐glucuronosyltransferases: Inhibition behaviours and implication in herb‐drug interactions[J]. Basic & Clinical Pharmacology & Toxicology, 2021, 129(6): 437-449.
[3]. Li, Z., Wu, Y. Y., & Yu, B. X. (2020). Methylophiopogonanone A, an Ophiopogon homoisoflavonoid, alleviates high-fat diet-induced hyperlipidemia: assessment of its potential mechanism. Brazilian Journal of Medical and Biological Research, 53.
[4]. Dang, N. H., Chung, N. D., Tuan, H. M., Hiep, N. T., & Dat, N. T. (2017). Cytotoxic homoisoflavonoids from Ophiopogon japonicus tubers. Chemical and Pharmaceutical Bulletin, 65(2), 204-207.
[5]. Lin, M., Sun, W., Gong, W., Zhou, Z., Ding, Y., & Hou, Q. (2015). Methylophiopogonanone a protects against cerebral ischemia/reperfusion injury and attenuates blood-brain barrier disruption in vitro. PLoS One, 10(4), e0124558.
[6]. He, F., Xu, B. L., Chen, C., Jia, H. J., Wu, J. X., Wang, X. C., ... & Cheng, J. (2016). Methylophiopogonanone A suppresses ischemia/reperfusion-induced myocardial apoptosis in mice via activating PI3K/Akt/eNOS signaling pathway. Acta Pharmacologica Sinica, 37(6), 763-771.
甲基麦冬酮 A (MOA) 是一种从草药麦冬中分离出来的具有丰富生物活性的同型异黄酮，被认为是麦冬相关草药制剂质量控制的关键化学指标[1]。甲基麦冬酮 A 抑制 4-HN-335 O-葡萄糖醛酸化的 hUGTs 效应，IC50 值范围为 1.23 ± 0.09 μμ（对于 UGT1A1）至 8.30 ± 0.72 μμ（对于 UGT2B7）[2]。
现代药理研究表明，甲基麦冬酮A具有多种药理作用，包括抗氧化、抗炎、抗肿瘤、抗高血脂等作用，具有减轻心肌细胞凋亡、改善脑缺血/再灌注损伤的潜力 < sup>[3,4,5,6].
甲基麦冬酮 A 剂量依赖性地抑制 HeLa-UGT1A1 细胞中 hUGT1A1 催化的 NHPN-O-葡萄糖醛酸化，表观 IC50 值为 1.54 ± 0.17 μM [2]。与模型组相比，甲基麦冬酮 A (2.5-10 μM) 处理显着逆转了降低的 TER 值，这表明甲基麦冬酮 A 对缺氧性 BBB 损伤具有保护作用[5]。在经过 H/R 处理的 H9C2 细胞中，用 Methylophiopogonanone A (10 μmol/L) 预处理可显着降低细胞凋亡和裂解的 caspase-3 表达，提高 Bcl-2/Bax 比率并恢复 NO 产生[6].
使用甲基麦冬花酮 A（10 mg.kg-1.d-1，口服）预处理可显着减少 I/R 患者的梗塞面积（减少 60.7%）和心肌细胞凋亡（减少 56.8%），并改善心脏功能小鼠[6]。甲基麦冬酮A（2.5 mg/kg和5.0 mg/kg）治疗组MCAO大鼠脑水含量低于模型组[5]。
| Cas No. | 74805-92-8 | SDF | |
| 别名 | 麦冬高异黄酮A | ||
| 化学名 | (3R)-3-(1,3-benzodioxol-5-ylmethyl)-5,7-dihydroxy-6,8-dimethyl-2,3-dihydrochromen-4-one | ||
| Canonical SMILES | CC1=C(C2=C(C(=C1O)C)OCC(C2=O)CC3=CC4=C(C=C3)OCO4)O | ||
| 分子式 | C19H18O6 | 分子量 | 342.34 |
| 溶解度 | ≥ 86.7mg/mL in DMSO | 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 | 2.9211 mL | 14.6054 mL | 29.2107 mL |
| 5 mM | 0.5842 mL | 2.9211 mL | 5.8421 mL |
| 10 mM | 0.2921 mL | 1.4605 mL | 2.9211 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。
Oxidation of methylophiopogonanone A on the surface of TLC plate
J Nat Med2022 Mar;76(2):504-508.PMID: 35089490DOI: 10.1007/s11418-022-01604-7
Methylophiopogonanone A (MOPNA, 1) is a characteristic homoisoflavonoid, having two methyl groups on the A ring, isolated from Ophiopogon Root (enlarged part of the root of Ophiopogon japonicus Ker-Gawler, Liliaceae). Although MOPNA is chemically stable in various organic solvents, such as acetone, chloroform, methanol and dimethyl sulfoxide, it gave a spot of higher polarity in addition to the spot of MOPNA on the surface of TLC plate. The spot was isolated and the structure of the major compound was revealed to be a compound with an oxygen atom at C-6 of the A ring. This oxidation on the surface of TLC plate was observed for synthetic intermediates of MOPNA having two methyl groups on a phloroacetophenone-type ring, suggesting that the methyl groups enhanced susceptibility to air oxidation. The structure of the major oxidation product was similar to those of humulone and sufflomin A. Humulone has two prenyl units and sufflomin A has two C-glucosyl moieties instead of the two methyl groups, respectively. As dialkylated phloroacetophenone derivatives seem susceptible to oxidation, air oxidation might be involved in the formation of these compounds.
Methylophiopogonanone A is a naturally occurring broad-spectrum inhibitor against human UDP-glucuronosyltransferases: Inhibition behaviours and implication in herb-drug interactions
Basic Clin Pharmacol Toxicol2021 Dec;129(6):437-449.PMID: 34478607DOI: 10.1111/bcpt.13651
Methylophiopogonanone A (MOA) is an abundant homoisoflavonoid in the Chinese herb Ophiopogonis Radix. Recent investigations revealed that MOA inhibited several human cytochrome P450 enzymes (CYPs) and stimulated OATP1B1. However, the inhibitory effects of MOA on phase II drug-metabolizing enzymes, such as human UDP-glucuronosyltransferases (hUGTs), have not been well investigated. Herein, the inhibition potentials of MOA on hUGTs were assessed. The results clearly demonstrated that MOA dose-dependently inhibited all tested hUGTs including UGT1A1 (IC50 = 1.23 米M), one of the most important detoxification enzymes in humans. Further investigations showed that MOA strongly inhibited UGT1A1-catalysed NHPH-O-glucuronidation in a range of biological settings including hUGT1A1, human liver microsomes (HLM) and HeLa cells overexpressing UGT1A1. Inhibition kinetic analyses demonstrated that MOA competitively inhibited UGT1A1-catalysed NHPH-O-glucuronidation in both hUGT1A1 and HLM, with Ki values of 0.52 and 1.22 米M, respectively. Collectively, our findings expanded knowledge of the interactions between MOA and human drug-metabolizing enzymes, which would be very helpful for guiding the use of MOA-related herbal products in clinical settings.
Methylophiopogonanone A, an Ophiopogon homoisoflavonoid, alleviates high-fat diet-induced hyperlipidemia: assessment of its potential mechanism
Braz J Med Biol Res2020 Mar 2;53(3):e9201.PMID: 32130294DOI: 10.1590/1414-431X20199201
Methylophiopogonanone A (MO-A), a homoisoflavonoid extracted from Ophiopogon japonicus, has been shown to attenuate myocardial apoptosis and improve cerebral ischemia/reperfusion injury. However, the hypolipidemic effects remain unknown. This study was performed to investigate a potential hypolipidemic effect of MO-A in hyperlipidemia rats, as well as its underlying mechanism of action. A rat model of hyperlipidemia was induced by a high-fat diet (HFD). Animals were randomly divided into three groups (n=8/group): normal control group (NC), HFD group, and HFD+MO-A (10 mg﹞kg-1﹞d-1) treatment group. The effects of MO-A on serum lipids, body weight, activity of lipoprotein metabolism enzyme, and gene expression of lipid metabolism were evaluated in HFD-induced rats. In HFD-induced rats, pretreatment with MO-A decreased the body weight gain and reduced serum and hepatic lipid levels. In addition, pretreatment with MO-A improved the activities of lipoprotein lipase and hepatic lipase in serum and liver, down-regulated mRNA expression of acetyl CoA carboxylase and sterol regulatory element-binding protein 1c, and up-regulated mRNA expression of low-density lipoprotein receptor and peroxisome proliferator-activated receptor 汿in the liver. Our results indicated that MO-A showed strong ability to ameliorate the hyperlipidemia in HFD-induced rats. MO-A might be a potential candidate for prevention of overweight and dyslipidemia induced by HFD.
Identification of the metabolites of methylophiopogonanone A by ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry
Rapid Commun Mass Spectrom2022 Jun 30;36(12):e9304.PMID: 35347765DOI: 10.1002/rcm.9304
Rationale: Methylophiopogonanone A (MOA) is a naturally occurring homoisoflavonoid from the Chinese herb Ophiopogon japonicus, which has been demonstrated to attenuate myocardial apoptosis. However, the metabolism of MOA remains unknown. The goal of the present work was to investigate the in vitro metabolism of MOA using liver microsomes and hepatocytes.
Methods: The metabolites were generated by incubating MOA with rat, monkey and human liver microsomes or hepatocytes. The resulting samples were analyzed by using a quadrupole-orbitrap high-resolution mass spectrometer. The metabolites were identified through the measurements of the exact mass, elemental composition and product ions.
Results: A total of 15 metabolites were detected and identified. Among these metabolites, M7 (demethylenation) was the most abundant metabolite in liver microsomes, while M6 (hydroxylation) was the predominant metabolite in hepatocytes, and glucuronidation metabolites (M9 and M10) were also the main metabolites in hepatocytes. The metabolic pathways of MOA included hydroxylation, demethylenation, glucuronidation, methylation, sulfation and glutathione conjugation.
Conclusions: This study for the first time provides valuable data on the metabolites of MOA, which will be of great importance for a better understanding of its disposition and to predict human pharmacokinetics.
Methylophiopogonanone A suppresses ischemia/reperfusion-induced myocardial apoptosis in mice via activating PI3K/Akt/eNOS signaling pathway
Acta Pharmacol Sin2016 Jun;37(6):763-71.PMID: 27063216DOI: 10.1038/aps.2016.14
Aim: The dried tuber root of Ophiopogon japonicus has been used in the traditional Chinese medicine for treatment of myocardial ischemia and thrombosis. In this study we investigated the effects of methylophiopogonanone A (MO-A), a major homoisoflavonoid in Ophiopogon japonicus, on myocardial ischemia/reperfusion (I/R) injury.
Methods: Mice were pretreated with MO-A (10 mg﹞kg(-1)﹞d(-1), po) for 2 weeks and then subjected to transient occlusion of the left anterior descending coronary artery. Cardiac function was evaluated, and the infarct size and apoptosis index were assessed. The mechanisms underlying the cardio-protection of MO-A were analyzed in H9C2 rat cardiomyocytes subjected to hypoxia/reoxygenation (H/R). The cell viability and apoptosis were evaluated; apoptotic and relevant signaling proteins were analyzed. NO levels in the culture medium were assessed.
Results: In I/R mice, pretreatment with MO-A significantly reduced the infarct size (by 60.7%) and myocardial apoptosis (by 56.8%), and improved cardiac function. In H9C2 cells subjected to H/R, pretreatment with MO-A (10 米mol/L) significantly decreased apoptosis and cleaved caspase-3 expression, elevated the Bcl-2/Bax ratio and restored NO production. Furthermore, pretreatment with MO-A markedly increased the activation of PI3K/Akt/eNOS pathway in H9C2 cells subjected to H/R, and the protective effects of MO-A were abolished in the presence of the PI3K inhibitor wortmannin (100 nmol/L).
Conclusion: MO-A attenuates I/R-induced myocardial apoptosis in mice via activating the PI3K/Akt/eNOS signaling pathway.