Isosakuranetin
(Synonyms: 异野樱素) 目录号 : GC30081
A citrus flavanone with diverse biological activities
Cas No.:480-43-3
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
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Cell experiment: |
B16 melanoma cells are cultured in 24-well plates at a density of 1×104 cells/well. After 24 h, the cells are incubated for 72 h in the presence of Isosakuranetin at the indicated concentrations. The culture medium is removed and replaced with 500 μL of fresh culture medium containing 10% sterile filtered MTT. After 3 h, the formazan crystals are dissolved in 500 μL/well isopropanol and absorbance is measured at 570 nm against 630 nm. Inhibition of proliferation (%) is expressed as the percentage of viable treated cells in comparison with control cells[1]. |
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Animal experiment: |
Male Sprague-Dawley rats weighing 250 to 300 g are habituated to the temperature, humidity, and lighting (12 h light/dark cycle, lights on at 7: 00 a.m.) controlled vivarium and singly housed for at least 1 week before the studies begin. The rotarod test is used to evaluate the potential motor-impairing effect of Isosakuranetin. For the time course studies, baseline measurement is immediately followed by an injection of Isosakuranetin, and then the paw-withdrawal threshold is measured every 15 min until the drug effect dissipates to a point that the paw withdrawal threshold is not significantly different from the predrug data or until 75 min passes[2]. |
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References: [1]. Drira R, et al. Isosakuranetin, a 4'-O-methylated flavonoid, stimulates melanogenesis in B16BL6 murine melanoma cells. Life Sci. 2015 Dec 15;143:43-9. |
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Isosakuranetin is a flavanone that has been found in Citrus species and has diverse biological activities.1,2,3,4,5,6,7 It inhibits calcium uptake induced by pregnenolone sulfate in HEK293 cells expressing mouse transient receptor potential melastatin 3 (TRPM3; IC50 = 50 nM).1 Isosakuranetin is selective for TRPM3 over TRPM1, TRPM8, and TRP vanilloid-related 1 (TRPV1) when used at a concentration of 10 μM. In vivo, isosakuranetin (2 mg/kg) increases latency to first pain-related response in mice in a hot plate test and reduces the number and duration of PregS-induced nocifensive responses, such as paw licking, shaking, or lifting, in mice. It also reduces systolic blood pressure in spontaneously hypertensive rats when administered at a dose of 10 mg/kg.2 Isosakuranetin (20 ?M) inhibits UV-B-induced matrix metalloproteinase-1 (MMP-1) expression by 90% in HaCaT human keratinocyte cells, as well as phosphorylation of ERK1/2 when used at a concentration of 50 ?M.3 It blocks hydrogen peroxide-induced increases in reactive oxygen species (ROS), intracellular calcium concentration, caspase-3 activity, and JNK phosphorylation, as well as decreases in catalase activity, in PC12 cells when used at a concentration of 0.8 ?M.4 Isosakuranetin also has antibacterial and trypanocidal activity against M. tuberculosis, C. neoformans, and T. cruzi.5,6,7
1.Straub, I., Krügel, U., Mohr, F., et al.Flavanones that selectively inhibit TRPM3 attenuate thermal nociception in vivoMol. Pharmacol.84(5)736-750(2013) 2.Maruyama, H., Sumitou, Y., Sakamoto, T., et al.Antihypertensive effects of flavonoids isolated from brazilian green propolis in spontaneously hypertensive ratsBiol. Pharm. Bull.32(7)1244-1250(2009) 3.Jung, H., Lee, E.H., Lee, T.H., et al.The methoxyflavonoid isosakuranetin suppresses UV-B-induced matrix metalloproteinase-1 expression and collagen degradation relevant for skin photoagingInt. J. Mol. Sci.17(9)E1449(2016) 4.Hwang, S.-L., and Yen, G.-C.Modulation of Akt, JNK, and p38 activation is involved in citrus flavonoid-mediated cytoprotection of PC12 cells challenged by hydrogen peroxideJ. Agric. Food Chem.57(6)2576-2582(2009) 5.Suksamrarn, A., Chotipong, A., Suavansri, T., et al.Antimycobacterial activity and cytotoxicity of flavonoids from the flowers of Chromolaena odorataArch. Pharm. Res.27(5)507-511(2004) 6.da Silva Filho, A.A., de Sousa, J.P., Soares, S., et al.Antimicrobial activity of the extract and isolated compounds from Baccharis dracunculifolia D. C. (Asteraceae)Z. Naturforsch. C.63(1-2)40-46(2008) 7.da Silva Filho, A.A., Pires Bueno, P.C., Gregório, L.E., et al.In-vitro trypanocidal activity evaluation of crude extract and isolated compounds from Baccharis dracunculifolia D.C. (Asteraceae)J. Pharm. Pharmacol.56(9)1195-1199(2004)
| Cas No. | 480-43-3 | SDF | |
| 别名 | 异野樱素 | ||
| Canonical SMILES | O=C1C[C@@H](C2=CC=C(OC)C=C2)OC3=CC(O)=CC(O)=C13 | ||
| 分子式 | C16H14O5 | 分子量 | 286.28 |
| 溶解度 | DMSO : 125 mg/mL (436.64 mM) | 储存条件 | Store at 2-8°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 | 3.4931 mL | 17.4654 mL | 34.9308 mL |
| 5 mM | 0.6986 mL | 3.4931 mL | 6.9862 mL |
| 10 mM | 0.3493 mL | 1.7465 mL | 3.4931 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。
Antinociceptive Effects of Isosakuranetin in a Rat Model of Peripheral Neuropathy
Pharmacology 2017;100(3-4):201-207.28715803 10.1159/000478986
Chronic pain remains a challenging clinical reality, yet currently available analgesics are insufficient to meet clinical needs. Increasing attention has been paid to bioactive compounds from natural plants, which may be efficacious against pain. This study examined the antinociceptive effects of Isosakuranetin, a plant-derived transient receptor potential melastatin 3 blocker, in a rat model of peripheral neuropathy. Adult male Sprague-Dawley rats were first allowed to go through the chronic constriction injury surgery to develop neuropathic pain. They were then treated with Isosakuranetin (1.5, 3, or 6 mg/kg) intraperitoneally and the effects on mechanical, thermal, and cold hyperalgesia were assessed using the von Frey filament test, Hargreaves' plantar test, and cold plate test, respectively. Isosakuranetin dose-dependently alleviated mechanical, thermal, and cold hyperalgesia and the antinociceptive potency was similar across the assays. In the rotarod test, Isosakuranetin did not significantly affect motor performance within the doses tested, confirming the antinociceptive specificity. In summary, these findings suggest that Isosakuranetin may be useful in treating neuropathic pain and deserves further investigation.
Flavanones: Citrus phytochemical with health-promoting properties
Biofactors 2017 Jul 8;43(4):495-506.28497905 10.1002/biof.1363
Citrus fruit and juices represent one of the main sources of compounds with a high potential for health promoting properties. Among these compounds, flavanones (such as hesperetin, naringenin, eriodictyol, Isosakuranetin, and their respective glycosides), which occur in quantities ranging from ∿80 to 740 mg/L (depending on the Citrus species and cultivar) are responsible for many biological activities. These compounds support and enhance the body's defenses against oxidative stress and help the organism in the prevention of cardiovascular diseases, atherosclerosis, and cancer. Moreover, among other properties, they also show anti-inflammatory, antiviral, and antimicrobial activities. This review analyzes the biochemistry, pharmacology, and biology of Citrus flavanones, emphasizing the occurrence in Citrus fruits and juices and their bioavailability, structure-function correlations and ability to modulate signal cascades both in vitro and in vivo. © 2017 BioFactors, 43(4):495-506, 2017.
Effects of Isosakuranetin on Pharmacokinetic Changes of Tofacitinib in Rats with N-Dimethylnitrosamine-Induced Liver Cirrhosis
Pharmaceutics 2022 Dec 1;14(12):2684.36559177 PMC9783783
Tofacitinib, a Janus kinase 1 and 3 inhibitor, is used to treat rheumatoid arthritis. It is mainly metabolized by the cytochromes p450 (CYP) 3A1/2 and CYP2C11 in the liver. Chronic inflammation eventually leads to cirrhosis in patients with rheumatoid arthritis. Isosakuranetin (ISN), a component of Citrus aurantium L., has hepatoprotective effects in rats. This study was performed to determine the effects of ISN on the pharmacokinetics of tofacitinib in rats with N-dimethylnitrosamine-induced liver cirrhosis (LC). After intravenous administration of 10 mg/kg tofacitinib to control (CON), LC, and LC treated with ISN (LC-ISN) rats, the total area under the plasma concentration-time curves (AUC) from time zero to infinity increased by 158% in LC rats compared to those in CON rats; however, the AUC of LC-ISN rats decreased by 35.1% compared to that of LC rat. Similar patterns of AUC changes were observed in the LC and LC-ISN rats after oral administration of 20 mg/kg tofacitinib. These results can be attributed to decreased non-renal clearance (CLNR) and intestinal intrinsic clearance (CLint) in the LC rats and increased intestinal and hepatic CLint in the LC-ISN rats. Our findings imply that ISN treatment in LC rats restored the decrease in either CLNR or CLint, or both, through increased hepatic and intestinal expression of CYP3A1/2 and CYP2C11, which is regulated by the induction of pregnane X receptor (PXR) and constitutive androstane receptor (CAR).
Isosakuranetin, a 4'-O-methylated flavonoid, stimulates melanogenesis in B16BL6 murine melanoma cells
Life Sci 2015 Dec 15;143:43-9.26524968 10.1016/j.lfs.2015.10.009
Aims: The beneficial effects of 4'-O-methylated flavonoids on induction of melanogenesis are well established. Here, we report the effect of Isosakuranetin (Iso) on melanogenesis in B16BL6 melanoma cells and an analysis of the signaling pathways involved in this activity. Methods: B16BL6 melanoma cells were treated with several concentrations of Iso and melanin content was measured. Activation and expression of factors involved in melanogenesis were assessed via western blotting. Key findings: Iso (15 and 30μmol/L) strongly stimulated melanogenesis in a dose-dependent manner. Iso increased tyrosinase activity and up-regulated tyrosinase (Tyr), tyrosinase related protein 1 (TRP1), and tyrosinase related protein 2 (TRP2) in a time-dependent manner. Iso decreased B16 cell proliferation at a concentration above 45μmol/L, and had no effect on cell viability as revealed by MTT and trypan blue assays. Iso up-regulated expression of microphthalmia transcription factor (MITF), with a maximum effect after 12h. H89, a specific inhibitor of PKA, showed that MITF up-regulation is mediated through PKA/CREB activation. Furthermore, Iso decreased phosphorylation of MITF at Ser73 after 24h and 48h of exposure, activating MITF and leading to up-regulation of Tyr, TRP1, and TRP2. Iso inhibited phosphorylation and activation of ERK1/2 after 12h, while no significant effects on p38 and JNK phosphorylation were observed. Iso inhibited AKT phosphorylation and led to activation of GSK3β. Significance: Iso stimulates melanogenesis in B16 melanoma cells via up-regulation of MITF. Furthermore, Iso-induced inhibition of ERK1/2 and PI3K/AKT signaling pathways activate MITF and subsequent expression of Tyr, TRP1, and TRP2.
The Methoxyflavonoid Isosakuranetin Suppresses UV-B-Induced Matrix Metalloproteinase-1 Expression and Collagen Degradation Relevant for Skin Photoaging
Int J Mol Sci 2016 Sep 1;17(9):1449.27598131 PMC5037728
Solar ultraviolet (UV) radiation is a main extrinsic factor for skin aging. Chronic exposure of the skin to UV radiation causes the induction of matrix metalloproteinases (MMPs), such as MMP-1, and consequently results in alterations of the extracellular matrix (ECM) and skin photoaging. Flavonoids are considered as potent anti-photoaging agents due to their UV-absorbing and antioxidant properties and inhibitory activity against UV-mediated MMP induction. To identify anti-photoaging agents, in the present study we examined the preventative effect of methoxyflavonoids, such as sakuranetin, Isosakuranetin, homoeriodictyol, genkwanin, chrysoeriol and syringetin, on UV-B-induced skin photo-damage. Of the examined methoxyflavonoids, pretreatment with Isosakuranetin strongly suppressed the UV-B-mediated induction of MMP-1 in human keratinocytes in a concentration-dependent manner. Isosakuranetin inhibited UV-B-induced phosphorylation of mitogen-activated protein kinase (MAPK) signaling components, ERK1/2, JNK1/2 and p38 proteins. This result suggests that the ERK1/2 kinase pathways likely contribute to the inhibitory effects of Isosakuranetin on UV-induced MMP-1 production in human keratinocytes. Isosakuranetin also prevented UV-B-induced degradation of type-1 collagen in human dermal fibroblast cells. Taken together, our findings suggest that Isosakuranetin has the potential for development as a protective agent for skin photoaging through the inhibition of UV-induced MMP-1 production and collagen degradation.