Nothofagin
(Synonyms: 1-(3-BETA-D-吡喃葡萄糖基-2,4,6-三羟基苯基)-3-(4-羟基苯基)-1-丙酮) 目录号 : GC61139
Nothofagin是一种二氢查尔酮，是从如意宝(Aspalathuslinearis)中分离得到的。Nothofagin通过阻断钙(calcium)内流来下调NF-κB的转运。Nothofagin具有抗氧化活性，可改善各种炎症反应，例如脓毒症反应和血管炎症。
Cas No.:11023-94-2
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Nothofagin, a dihydrochalcone, is isolated from rooibos (Aspalathus linearis)[1]. Nothofagin downregulates NF-κB translocation through blocking calcium influx. Nothofagin has antioxidant activity and ameliorates various inflammatory responses such as the septic response and vascular inflammation[2].
Nothofagin pre-treatment (0.1, 1, 10 μM) decreases the level of histamine release in RBL-2H3 and RPMCs cells. The production of cytokines are downregulated bynothofagin pre-treatment Nothofagin (TNF-α: 1-10 μM; IL-4: 0.1-10 μM, IL-6: 1-10 μM)[1]. Pre-treatment of DNPHSA-stimulated RBL-2H3 with Nothofagin (10 μM) markedly suppresses the phosphorylation of Lyn, Syk, and Akt[1]. Nothofagin (30 μM; for 6 hours) results in inhibited formation of LPS-induced (100 ng/mL; 4 hours) paracellular gaps with the formation of dense F-actin rings in HUVECs[2]. Nothofagin suppresses IgE-mediated mast cell degranulation both in vitro and in vivo[1].
Nothofagin (1 mg/kg; orally; once a day; for 7 days) significantly increases the urinary volume of both normotensive (NTR) and spontaneously hypertensive rats (SHR)[3]. Animal Model: Male Wistar normotensive and spontaneously hypertensive rats (3-4 months old) [3]
[1]. Wonhwa Lee, et al. Anti-inflammatory Effects of Aspalathin and Nothofagin From Rooibos (Aspalathus Linearis) In Vitro and In Vivo. Inflammation. 2015 Aug;38(4):1502-16. [2]. Byeong-Cheol Kang, et al. Nothofagin Suppresses Mast Cell-Mediated Allergic Inflammation. Chem Biol Interact. 2019 Jan 25;298:1-7. [3]. Camila Leandra Bueno de Almeida, et al. Prolonged Diuretic and Saluretic Effect of Nothofagin Isolated From Leandra Dasytricha (A. Gray) Cogn. Leaves in Normotensive and Hypertensive Rats: Role of Antioxidant System and Renal Protection. Chem Biol Interact. 2018 Jan 5;279:227-233.
| Cas No. | 11023-94-2 | SDF | |
| 别名 | 1-(3-BETA-D-吡喃葡萄糖基-2,4,6-三羟基苯基)-3-(4-羟基苯基)-1-丙酮 | ||
| Canonical SMILES | OC1=C([C@@H]([C@@H]([C@H]2O)O)O[C@@H]([C@H]2O)CO)C(O)=CC(O)=C1C(CCC(C=C3)=CC=C3O)=O | ||
| 分子式 | C21H24O10 | 分子量 | 436.41 |
| 溶解度 | 储存条件 | Store at -20°C | |
| 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2914 mL | 11.4571 mL | 22.9142 mL |
| 5 mM | 0.4583 mL | 2.2914 mL | 4.5828 mL |
| 10 mM | 0.2291 mL | 1.1457 mL | 2.2914 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。
Nothofagin suppresses mast cell-mediated allergic inflammation
Chem Biol Interact 2019 Jan 25;298:1-7.PMID:30392763DOI:10.1016/j.cbi.2018.10.025.
Mast cells play a major role in immunoglobulin E-mediated allergic inflammation, which is involved in asthma, atopic dermatitis, and allergic rhinitis. Nothofagin has been shown to ameliorate various inflammatory responses such as the septic response and vascular inflammation. In this study, we assessed the inhibitory effect of Nothofagin on allergic inflammation using cultured/isolated mast cells and an anaphylaxis mouse model. Nothofagin treatment prevented histamine and β-hexosaminidase release by reducing the influx of calcium into the cytosol in a concentration-dependent manner. Nothofagin also inhibited the gene expression and secretion of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-4 by downregulating the phosphorylation of Lyn, Syk, Akt and nuclear translocation of nuclear factor-κB. To confirm these effects of Nothofagin in vivo, we used a passive cutaneous anaphylaxis mouse model. Topical administration of Nothofagin suppressed local pigmentation and ear thickness. Taken together, these results suggest Nothofagin as a potential candidate for the treatment of mast cell-involved allergic inflammatory diseases.
Nitric oxide/cGMP signaling pathway and potassium channels contribute to hypotensive effects of Nothofagin
Minerva Cardioangiol 2020 Dec;68(6):602-608.PMID:32657557DOI:10.23736/S0026-4725.20.05243-3.
Background: Nothofagin is a mono-C-glycoside of 4,2',4',6'-tetrahydroxy-dihydrochalcone that is commonly found in Aspalathus linearis, Nothofagus fusca, and Leandra dasytricha. A wide range of biological effects has been attributed to Nothofagin, including antioxidant, diuretic, renoprotective, antiplatelet, and antithrombotic effects. Although Nothofagin is pharmacologically active, its effects on blood pressure remain unknown. In the present study, we investigated whether Nothofagin causes acute and prolonged hypotension in male Wistar rats, and we investigated the molecular mechanisms that underlie these hemodynamic effects. Methods: Hypotensive effects of Nothofagin (0.3, 1, and 3 mg/kg) were evaluated after acute intraduodenal administration and after 7 days of oral treatment. Using pharmacological antagonists and inhibitors, we explored the involvement of the prostaglandin/cyclic adenosine monophosphate and nitric oxide/cyclic guanosine monophosphate pathways and K+ channels in nothofagin-induced hypotension. Results: Acute and prolonged Nothofagin administration significantly decreased systolic blood pressure and mean arterial pressure in Wistar rats. Pretreatment with N(G)-nitro-L-arginine methyl ester, methylene blue, and tetraethylammonium prevented the hypotensive effect of Nothofagin. Conclusions: These results show that Nothofagin induces a hypotensive response in Wistar rats, and this effect depends on K+ channel opening in smooth muscle cells through nitric oxide signaling.
Leloir glycosyltransferases enabled to flow synthesis: Continuous production of the natural C-glycoside Nothofagin
Biotechnol Bioeng 2021 Nov;118(11):4402-4413.PMID:34355386DOI:10.1002/bit.27908.
C-glycosyltransferase (CGT) and sucrose synthase (SuSy), each fused to the cationic binding module Zbasic2 , were co-immobilized on anionic carrier (ReliSorb SP400) and assessed for continuous production of the natural C-glycoside Nothofagin. The overall reaction was 3'-C-β-glycosylation of the polyphenol phloretin from uridine 5'-diphosphate (UDP)-glucose that was released in situ from sucrose and UDP. Using solid catalyst optimized for total (∼28 mg/g) as well as relative protein loading (CGT/SuSy = ∼1) and assembled into a packed bed (1 ml), we demonstrate flow synthesis of Nothofagin (up to 52 mg/ml; 120 mM) from phloretin (≥95% conversion) solubilized by inclusion complexation in hydroxypropyl β-cyclodextrin. About 1.8 g Nothofagin (90 ml; 12-26 mg/ml) were produced continuously over 90 reactor cycles (2.3 h/cycle) with a space-time yield of approximately 11 mg/(ml h) and a total enzyme turnover number of up to 2.9 × 103 mg/mg (=3.8 × 105 mol/mol). The co-immobilized enzymes exhibited useful effectiveness (∼40% of the enzymes in solution), with limitations on the conversion rate arising partly from external liquid-solid mass transfer of UDP under packed-bed flow conditions. The operational half-life of the catalyst (∼200 h; 30°C) was governed by the binding stability of the glycosyltransferases (≤35% loss of activity) on the solid carrier. Collectively, the current study shows integrated process technology for flow synthesis with co-immobilized sugar nucleotide-dependent glycosyltransferases, using efficient glycosylation from sucrose via the internally recycled UDP-glucose. This provides a basis from engineering science to promote glycosyltransferase applications for natural product glycosides and oligosaccharides.
Nitric oxide and Ca2+-activated high-conductance K+ channels mediate nothofagin-induced endothelium-dependent vasodilation in the perfused rat kidney
Chem Biol Interact 2020 Aug 25;327:109182.PMID:32554038DOI:10.1016/j.cbi.2020.109182.
Nothofagin is a natural 3'-C-β-D-glucoside of the polyphenol phloretin that is mainly found in Aspalathus linearis, Nothofagus fusca, and Leandra dasytricha. In recent years, Nothofagin has been described as a potential therapeutic agent for renal disorders, but the mechanisms that are involved in its renoprotective effects remain unclear. In the present study, perfused rat kidneys were used to test the hypothesis that Nothofagin causes the direct relaxation of renal arteries. The molecular mechanisms that underlie these vascular effects were also investigated. The left kidney from Wistar rats was coupled in a perfusion system and continuously perfused with physiological saline solution (PSS). Initially, preparations with and without the endothelium were contracted with phenylephrine and received injections of 1-300 nmol Nothofagin. The preparations were then perfused with PSS that contained phenylephrine plus KCl, indomethacin, l-NAME, tetraethylammonium, glibenclamide, 4-aminopyridine, iberiotoxin, charybdotoxin, and apamin. After 15 min under perfusion, Nothofagin was injected again. In preparations with an intact endothelium, Nothofagin dose-dependently reduced perfusion pressure. Endothelium removal or the inhibition of nitric oxide synthase by l-NAME prevented the vasodilatory effect of Nothofagin at all doses tested. Perfusion with PSS that contained KCl or tetraethylammonium chloride also abolished the vasodilatory effect of Nothofagin. Treatment with glibenclamide, 4-aminopyridine, and apamin did not affect the vasodilatory effect of Nothofagin. Iberiotoxin (selective Ca2+-activated high-conductance K+ channel [KCa1.1] blocker) and charybdotoxin (selective KCa1.1 and Ca2+-activated intermediate-conductance K+ channel [KCa3.1] blocker) application blocked the vasodilatory effect of Nothofagin at all doses tested, pointing to a predominant role for KCa1.1 in the action of Nothofagin. However, these data cannot exclude a potential contribution of endothelial KCa3.1 channel in the nothofagin-induced vasodilation. Overall, our findings indicate that Nothofagin induces vasodilation in renal arteries, an effect that is mediated by Ca2+ -activated high-conductance K+ channels opening and endothelial nitric oxide production.
Isolation of aspalathin and Nothofagin from rooibos (Aspalathus linearis) using high-performance countercurrent chromatography: sample loading and compound stability considerations
J Chromatogr A 2015 Feb 13;1381:29-36.PMID:25614190DOI:10.1016/j.chroma.2014.12.078.
Aspalathin and Nothofagin, the major dihydrochalcones in rooibos (Aspalathus linearis), are valuable bioactive compounds, but their bioactivity has not been fully elucidated. Isolation of these compounds using high-performance countercurrent chromatography (HPCCC), a gentle, support-free, up-scalable technique, offers an alternative to synthesis for obtaining sufficient amounts. An HPLC-DAD method was adapted to allow rapid (16 min from injection to injection) quantification of the four major compounds (aspalathin, Nothofagin, isoorientin, orientin) during development of the isolation protocol. The traditional shake-flask method, used to determine distribution constants (K(D)) for target compounds, was also adapted to obtain higher repeatability. Green rooibos leaves with a high aspalathin and Nothofagin content were selected as source material. Sample loading of the polyphenol-enriched extract was limited due to constituents with emulsifying properties, but could be increased by removing ethanol-insoluble matter. Furthermore, problems with degradation of aspalathin during HPCCC separation and further processing could be limited by acidifying the HPCCC solvent system. Aspalathin was shown to be fairly stable at pH 3 (91% remaining after 29 h) compared to pH 7 (45% remaining after 29 h). Aspalathin and Nothofagin with high purities (99% and 100%, respectively) were obtained from HPCCC fractions after semi-preparative HPLC.