Garcinoic Acid
(Synonyms: δ-Garcinoic Acid, δ-trans-Tocotrienoloic Acid) 目录号 : GC46150
A derivative of vitamin E
Cas No.:91893-83-3
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
Garcinoic acid is a derivative of vitamin E originally isolated from C. grandiflora.1 It inhibits IL-1β-induced microsomal prostaglandin E2 synthase-1 (mPGES-1) activity in A549 cells when used at concentrations of 1 and 10 μM.2 It has higher antioxidant activity relative to (±)-α-tocopherol in a cell-free assay when used at a concentration of 0.15 mM.3
|1. Monache, F.D., Marta, M., Mac-Quhae, M.M., et al. Two new tocotrienoloic acids from the fruits of Clusia grandiflora Splith. Gazz. Chim. Ital. 114(3-4), 135-137 (1984).|2. Alsabil, K., Suor-Cherer, S., Koeberle, A., et al. Semisynthetic and natural garcinoic acid isoforms as new mPGES-1 inhibitors. Planta Med. 82(11-12), 1110-1116 (2016).|3. Terashima, K., Takaya, Y., and Niwa, M. Powerful antioxidative agents based on garcinoic acid from Garcinia kola. Bioorg. Med. Chem. 10(5), 1619-1625 (2002).
| Cas No. | 91893-83-3 | SDF | |
| 别名 | δ-Garcinoic Acid, δ-trans-Tocotrienoloic Acid | ||
| Canonical SMILES | OC1=CC(C)=C2C(CC[C@](CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/C(O)=O)(C)O2)=C1 | ||
| 分子式 | C27H38O4 | 分子量 | 426.6 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:3): 0.25 mg/ml,Ethanol: 30 mg/ml | 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。 |
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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 | 2.3441 mL | 11.7206 mL | 23.4412 mL |
| 5 mM | 0.4688 mL | 2.3441 mL | 4.6882 mL |
| 10 mM | 0.2344 mL | 1.1721 mL | 2.3441 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。
Garcinoic Acid Is a Natural and Selective Agonist of Pregnane X Receptor
J Med Chem 2020 Apr 9;63(7):3701-3712.PMID:32160459DOI:10.1021/acs.jmedchem.0c00012.
Pregnane X receptor (PXR) is a master xenobiotic-sensing transcription factor and a validated target for immune and inflammatory diseases. The identification of chemical probes to investigate the therapeutic relevance of the receptor is still highly desired. In fact, currently available PXR ligands are not highly selective and can exhibit toxicity and/or potential off-target effects. In this study, we have identified Garcinoic Acid as a selective and efficient PXR agonist. The properties of this natural molecule as a specific PXR agonist were demonstrated by the screening on a panel of nuclear receptors, the assessment of the physical and thermodynamic binding affinity, and the determination of the PXR-garcinoic acid complex crystal structure. Cytotoxicity, transcriptional, and functional properties were investigated in human liver cells, and compound activity and target engagement were confirmed in vivo in mouse liver and gut tissue. In conclusion, Garcinoic Acid is a selective natural agonist of PXR and a promising lead compound toward the development of new PXR-regulating modulators.
Garcinoic Acid prevents β-amyloid (Aβ) deposition in the mouse brain
J Biol Chem 2020 Aug 14;295(33):11866-11876.PMID:32616652DOI:10.1074/jbc.RA120.013303.
Garcinoic Acid (GA or δ-T3-13'COOH), is a natural vitamin E metabolite that has preliminarily been identified as a modulator of nuclear receptors involved in β-amyloid (Aβ) metabolism and progression of Alzheimer's disease (AD). In this study, we investigated GA's effects on Aβ oligomer formation and deposition. Specifically, we compared them with those of other vitamin E analogs and the soy isoflavone genistein, a natural agonist of peroxisome proliferator-activated receptor γ (PPARγ) that has therapeutic potential for managing AD. GA significantly reduced Aβ aggregation and accumulation in mouse cortical astrocytes. Similarly to genistein, GA up-regulated PPARγ expression and apolipoprotein E (ApoE) efflux in these cells with an efficacy that was comparable with that of its metabolic precursor δ-tocotrienol and higher than those of α-tocopherol metabolites. Unlike for genistein and the other vitamin E compounds, the GA-induced restoration of ApoE efflux was not affected by pharmacological inhibition of PPARγ activity, and specific activation of pregnane X receptor (PXR) was observed together with ApoE and multidrug resistance protein 1 (MDR1) membrane transporter up-regulation in both the mouse astrocytes and brain tissue. These effects of GA were associated with reduced Aβ deposition in the brain of TgCRND8 mice, a transgenic AD model. In conclusion, GA holds potential for preventing Aβ oligomerization and deposition in the brain. The mechanistic aspects of GA's properties appear to be distinct from those of other vitamin E metabolites and of genistein.
Garcinia kola and Garcinoic Acid suppress SARS-CoV-2 spike glycoprotein S1-induced hyper-inflammation in human PBMCs through inhibition of NF-κB activation
Phytother Res 2021 Dec;35(12):6963-6973.PMID:34697842DOI:10.1002/ptr.7315.
Symptoms and complications associated with severe SARS-CoV-2 infection such as acute respiratory distress syndrome (ARDS) and organ damage have been linked to SARS-CoV-2 spike protein S1-induced increased production of pro-inflammatory cytokines by immune cells. In this study, the effects of an extract of Garcinia kola seeds and Garcinoic Acid were investigated in SARS-CoV-2 spike protein S1-stimulated human PBMCs. Results of ELISA experiments revealed that Garcinia kola extract (6.25, 12.5, and 25 μg/ml) and Garcinoic Acid (1.25, 2.5, and 5 μM) significantly reduced SARS-CoV-2 spike protein S1-induced secretion of TNFα, IL-6, IL-1β, and IL-8 in PBMCs. In-cell western assays showed that pre-treatment with Garcinia kola extract and Garcinoic Acid reduced expressions of both phospho-p65 and phospho-IκBα proteins, as well as NF-κB DNA binding capacity and NF-κB-driven luciferase expression following stimulation of PBMCs with spike protein S1. Furthermore, pre-treatment of PBMCs with Garcinia kola extract prior to stimulation with SARS-CoV-2 spike protein S1 resulted in reduced damage to adjacent A549 lung epithelial cells. These results suggest that the seed of Garcinia kola and Garcinoic Acid are natural products which may possess pharmacological/therapeutic benefits in reducing cytokine storm in severe SARS-CoV-2 and other coronavirus infections.
Semisynthetic and Natural Garcinoic Acid Isoforms as New mPGES-1 Inhibitors
Planta Med 2016 Jul;82(11-12):1110-6.PMID:27286327DOI:10.1055/s-0042-108739.
Over the last twenty years, tocotrienol analogues raised great interest because of their higher level and larger domain of biological activities when compared with tocopherols. Amongst the most promising therapeutic application, anti-inflammatory potency has been evaluated through the inhibition of various mediators of inflammation. Here, we worked on the isolation of two natural isoforms of Garcinoic Acid (i.e., δ and γ) from two different sources, respectively, Garcinia kola seeds and Garcinia amplexicaulis bark. We also developed semisynthetic strategies to access the other two non-natural α- and β-garcinoic acid isoforms. In the next stage of our work, microsomal prostaglandin E2 synthase was defined as a target to evaluate the anti-inflammatory potential of the four Garcinoic Acid isomers. Both dimethylated isoforms, β- and γ-garcinoic acid, exhibited the lowest IC50, 2.8 µM and 2.0 µM, respectively. These results showed that the affinity of tocotrienol analogues to microsomal prostaglandin E2 synthase-1 most probably contributes to the anti-inflammatory potential of this class of derivatives.
A Facile Semisynthesis and Evaluation of Garcinoic Acid and Its Analogs for the Inhibition of Human DNA Polymerase β
Molecules 2020 Dec 11;25(24):5847.PMID:33322249DOI:10.3390/molecules25245847.
Garcinoic Acid has been identified as an inhibitor of DNA polymerase β (pol β). However, no structure-activity relationship (SAR) studies of Garcinoic Acid as a pol β inhibitor have been conducted, in part due to the lack of an efficient synthetic method for this natural product and its analogs. We developed an efficient semi-synthetic method for Garcinoic Acid and its analogs by starting from natural product δ-tocotrienol. Our preliminary SAR studies provided a valuable insight into future discovery of garcinoic acid-based pol β inhibitors.