Thonningianin A
目录号 : GC39094
Thonningianin A 是一种鞣花素，从非洲草药通宁宁的甲醇提取物中分离得到。Thonningianin A 的抗氧化特性包括自由基清除、抗超氧物生成和金属螯合作用。具有抗癌活性。
Cas No.:271579-11-4
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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Thonningianin A, an ellagitannin, is isolated from the methanolic extract of the African medicinal herb, Thonningia sanguinea. The antioxidant properties of Th A involve radical scavenging, anti-superoxide formation and metal chelation. Anti-cancer activities[1][2].
[1]. Gyamfi MA, et al. Antioxidant properties of Thonningianin A, isolated from the African medicinal herb, Thonningia sanguinea. Biochem Pharmacol. 2002 May 1;63(9):1725-37. [2]. Zhang TT, et al. Effects of thonningianin A in natural foods on apoptosis and cell cycle arrest of HepG-2 human hepatocellular carcinoma cells. Food Funct. 2015 Aug;6(8):2588-97.
| Cas No. | 271579-11-4 | SDF | |
| Canonical SMILES | OC1=CC(C(OC[C@@H]2[C@@H]3[C@H](OC(C4=CC(O)=C(O)C(O)=C4)=O)[C@@H](O)[C@H](OC5=CC(O)=C(C(CCC6=CC=CC=C6)=O)C(O)=C5)O2)=O)=C(C7=C(C(O3)=O)C=C(O)C(O)=C7O)C(O)=C1O | ||
| 分子式 | C42H34O21 | 分子量 | 874.71 |
| 溶解度 | Soluble 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。 |
||
| 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 | 1.1432 mL | 5.7162 mL | 11.4324 mL |
| 5 mM | 0.2286 mL | 1.1432 mL | 2.2865 mL |
| 10 mM | 0.1143 mL | 0.5716 mL | 1.1432 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。
Targeting microglial autophagic degradation of the NLRP3 inflammasome for identification of Thonningianin A in Alzheimer's disease
Inflamm Regen 2022 Aug 3;42(1):25.PMID:35918778DOI:10.1186/s41232-022-00209-7.
Background: NLRP3 inflammasome-mediated neuroinflammation plays a critical role in the pathogenesis and development of Alzheimer's disease (AD). Microglial autophagic degradation not only decreases the deposits of extracellular Aβ fibrils but also inhibits the activation of NRLP3 inflammasome. Here, we aimed to identify the potent autophagy enhancers from Penthorum chinense Pursh (PCP) that alleviate the pathology of AD via inhibiting the NLRP3 inflammasome. Methods: At first, autophagic activity-guided isolation was performed to identify the autophagy enhancers in PCP. Secondly, the autophagy effect was monitored by detecting LC3 protein expression using Western blotting and the average number of GFP-LC3 puncta per microglial cell using confocal microscopy. Then, the activation of NLRP3 inflammasome was measured by detecting the protein expression and transfected fluorescence intensity of NLRP3, ASC, and caspase-1, as well as the secretion of proinflammatory cytokines. Finally, the behavioral performance was evaluated by measuring the paralysis in C. elegans, and the cognitive function was tested by Morris water maze (MWM) in APP/PS1 mice. Results: Four ellagitannin flavonoids, including pinocembrin-7-O-[4″,6″-hexahydroxydiphenoyl]-glucoside (PHG), pinocembrin-7-O-[3″-O-galloyl-4″,6″-hexahydroxydiphenoyl]-glucoside (PGHG), Thonningianin A (TA), and thonningianin B (TB), were identified to be autophagy enhancers in PCP. Among these, TA exhibited the strongest autophagy induction effect, and the mechanistic study demonstrated that TA activated autophagy via the AMPK/ULK1 and Raf/MEK/ERK signaling pathways. In addition, TA effectively promoted the autophagic degradation of NLRP3 inflammasome in Aβ(1-42)-induced microglial cells and ameliorated neuronal damage via autophagy induction. In vivo, TA activated autophagy and improved behavioral symptoms in C. elegans. Furthermore, TA might penetrate the blood-brain barrier and could improve cognitive function and ameliorate the Aβ pathology and the NLRP3 inflammasome-mediated neuroinflammation via the AMPK/ULK1 and Raf/MEK/ERK signaling pathways in APP/PS1 mice. Conclusion: We identified TA as a potent microglial autophagy enhancer in PCP that promotes the autophagic degradation of the NLRP3 inflammasome to alleviate the pathology of AD via the AMPK/ULK1 and Raf/MEK/ERK signaling pathways, which provides novel insights for TA in the treatment of AD.
Quantification of Thonningianin A in rat plasma by liquid chromatography tandem mass spectrometry and its application to a pharmacokinetic study
Pharm Biol 2021 Dec;59(1):525-531.PMID:33915063DOI:10.1080/13880209.2021.1913188.
Context: Thonningianin A is an ellagitannin substance and displays multiple pharmacological activities. Objective: This study investigated the pharmacokinetic characteristics of Thonningianin A after oral administration in rats using a fully validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Materials and methods: A sensitive and selective LC-MS/MS assay was developed for quantifying Thonningianin A. Eighteen Wistar rats were randomly divided into three groups (n = 6), which were given at a single dose of 10, 20, or 40 mg/kg Thonningianin A by gavage. Blood samples (200 µL) were collected from the orbit vein at designated time points and analyzed using the LC-MS/MS method to measure the levels of Thonningianin A. Results: Thonningianin A and internal standard (IS) were eluted at 1.5 and ∼3.0 min, respectively. The selected reaction mode transitions monitored were m/z 873.2 > 300.3 and 819.3 > 610.6 for Thonningianin A and the IS, respectively. The calibration range was 10-1200 ng/mL. The intra- and the inter-day accuracy and precision met the acceptance criteria. No carryover and matrix effect were observed. The plasma concentrations of Thonningianin A increased rapidly after oral administration of three dosages and reached the mean peak concentrations (Cmax) within 0.61-0.83 h. Meanwhile, AUC0-t/AUC0-∞ of the three dosage groups was more than 89.0% (10 mg/kg), 95.7% (20 mg/kg), and 97.0% (40 mg/kg). Discussion and conclusions: The present method is the first report in terms of the simple precipitation procedure, high sensitivity, and high-throughput efficiency. This validated assay was successfully applied to determine the pharmacokinetic behaviours of Thonningianin A in rats. This study should be helpful for providing references for understanding the action mechanism and further application of Penthorum chinense.
Activation of Atg7-dependent autophagy by a novel inhibitor of the Keap1-Nrf2 protein-protein interaction from Penthorum chinense Pursh. attenuates 6-hydroxydopamine-induced ferroptosis in zebrafish and dopaminergic neurons
Food Funct 2022 Jul 18;13(14):7885-7900.PMID:35776077DOI:10.1039/d2fo00357k.
The death of dopaminergic neurons is a dominant factor during the occurrence and development of Parkinson's disease (PD). Previous studies demonstrated that ferroptosis is implicated in the death of dopaminergic neurons. Besides, polyphenols have been proven to be effective in preventing the death of dopaminergic neurons. This work aims to explore the neuroprotective effect and mechanism of Thonningianin A (Th A), a polyphenolic compound in natural plant foods, against 6-hydroxydopamine (6-OHDA)-induced ferroptosis in dopaminergic cells. The results of molecular docking and other binding assays collectively demonstrated that Th A can strongly target the Kelch domain of Keap1. Th A treatment significantly facilitated the nuclear factor erythroid 2-like 2 (Nrf2) nuclear translocation and subsequently increased the heme oxygenase-1 (HO-1) protein level through inhibiting the protein-protein interaction (PPI) of Keap1 and Nrf2. Compared with the nomifensine (Nomi) treatment, Th A had a more potent protective effect on 6-OHDA-induced ferroptosis during PD pathology in zebrafish, which was associated with assuaging the reduction of the total swimming distance, glutathione (GSH) depletion, iron accumulation, lipid peroxidation, and aggregation of α-synuclein (α-syn). Furthermore, Th A also exhibited a strong protective effect against 6-OHDA-induced ferroptosis in vitro in the human neuroblastoma cell line SH-SY5Y. Th A degraded Keap1 protein through activating Atg7-dependent autophagy. Additionally, Th A treatment facilitated the degradation of Keap1 protein by promoting the interaction between p62/SQSTM1 (sequestosome 1, hereafter referred to as p62) and Keap1. Taken together, our findings indicated that Th A protects dopaminergic cells against 6-OHDA-induced ferroptosis through activating the Nrf2-based cytoprotective system, thus enabling a potential application of Keap1-Nrf2 PPI inhibitors in the restraint of ferroptosis and treatment of PD.
Effects of Thonningianin A in natural foods on apoptosis and cell cycle arrest of HepG-2 human hepatocellular carcinoma cells
Food Funct 2015 Aug;6(8):2588-97.PMID:26119846DOI:10.1039/c5fo00388a.
The anti-cancer activities of Thonningianin A on the HepG-2 human hepatocellular carcinoma cell line were evaluated by MTT assay, flow cytometry, quantitative real-time PCR and western blotting. Results showed that Thonningianin A effectively inhibited the proliferation of HepG-2 cells by inducing apoptosis, as evidenced by increase in the sub-G1 cell population, DNA fragmentation, and increase in the content of reactive oxygen species. Activation of caspase-9 and the subsequent activation of caspase-3 indicated that Thonningianin A-induced apoptosis is caspase-dependent. Thonningianin A also disrupted the mitochondrial membrane potential (Δψm) and down-regulated the Bcl-xL mRNA expression in HepG-2 cells. Thonningianin A induced cell cycle arrest by changing the cyclin D1 and CDK4 mRNA expression levels. Moreover, western blotting showed that Thonningianin A significantly down-regulated the NF-kappa-B cell survival pathway, along with up-regulation of the expression level of phosphorylated P38 and down-regulation of the expression level of phosphorylated ERK. The anti-cancer activity of Thonningianin A was confirmed by the characteristic patterns of DNA fragmentation and cell cycle arrest, suggesting that Th A is an effective antitumor ingredient in natural plant foods, and is worthy of further study.
Antioxidant properties of Thonningianin A, isolated from the African medicinal herb, Thonningia sanguinea
Biochem Pharmacol 2002 May 1;63(9):1725-37.PMID:12007576DOI:10.1016/s0006-2952(02)00915-2.
The antioxidant properties of Thonningianin A (Th A), an ellagitannin, isolated from the methanolic extract of the African medicinal herb, Thonningia sanguinea were studied using the NADPH and Fe2+/ascorbate-induced lipid peroxidation (LPO), electron spin resonance spectrometer and the deoxyribose assay. Th A at 10 microM inhibited both the NADPH and Fe2+/ascorbate-induced LPO in rat liver microsomes by 60% without inhibitory effects on cytochrome P450 activity. Th A was similar to the synthetic antioxidant, tannic acid, as an inhibitor of both the NADPH and Fe2+/ascorbate-induced LPO but potent than gallic acid, vitamin C and vitamin E. While Th A poorly scavenged the hydroxyl radical generated by the Fenton reaction it dose-dependently scavenged 1,1-diphenyl-2-picrylhydrazyl, superoxide anion and peroxyl radicals with IC50 of 7.5, 10 and 30 microM, respectively. Furthermore, Th A showed inhibitory effects on the activity of xanthine oxidase with an IC50 of 30 microM. In the deoxyribose assay both T. sanguinea and its methanolic component Th A showed only site-specific (Fe3+ + H2O2) but not non-site-specific (Fe3+ + EDTA + H2O2) hydroxyl radical scavenging suggesting chelating ability for iron ions. Spectroscopic studies showed that Th A enhanced absorbance in the visible region in the presence of Fe2+ ions. These results indicate that the antioxidant properties of Th A involve radical scavenging, anti-superoxide formation and metal chelation.