Chebulagic acid
(Synonyms: 诃子鞣酸) 目录号 : GC31707
A polyphenol with diverse biological activities
Cas No.:23094-71-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Chebulagic acid is a polyphenol and tannin that has been found in T. chebula and has diverse biological activities.1,2,3,4,5 It is an inhibitor of COX-1, COX-2, and 5-lipoxygenase (5-LO; IC50s = 15, 0.92, and 2.1 μM, respectively) as well as α-glucosidase and 15-LO (IC50s = 0.05 and 24.9 μM, respectively).1,2 Chebulagic acid inhibits LPS-induced increases in inducible nitric oxide synthase (iNOS), COX-1, COX-2, and 5-LO protein levels, production of NO, prostaglandin E2 (PGE2), and reactive oxygen species (ROS), and nuclear translocation of NF-κB in RAW 264.7 macrophages in a concentration-dependent manner.3 It inhibits the growth of HCT15, COLO 205, MDA-MB-231, DU145, and K562 cancer cells (GI50s = 20.3, 18, 26.2, 28.54, and 30.66 μM, respectively).1 Chebulagic acid increases insulin-stimulated glucose uptake in 3T3-L1 adipocytes by 10.2-, 13.8-, and 16.6-fold when used at concentrations of 10, 50, and 100 μM, respectively.4 It also scavenges 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (IC50 = 1.4 μM) and exhibits antiviral activity against cytomegalovirus, hepatitis C virus, dengue virus, measles virus, and respiratory syncytial virus in vitro (EC50s = 25.5, 12.16, 13.11, 34.42, and 0.38 μM, respectively).1,5
1.Reddy, D.B., Reddy, T.C., Jyotsna, G., et al.Chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of Terminalia chebula retz., induces apoptosis in COLO-205 cell lineJ. Ethnopharmacol.124(3)506-512(2009) 2.Pham, A.T., Malterud, K.E., Paulsen, B.S., et al.α-Glucosidase inhibition, 15-lipoxygenase inhibition, and brine shrimp toxicity of extracts and isolated compounds from Terminalia macroptera leavesPharm. Biol.52(9)1166-1169(2014) 3.Reddy, D.B., and Reddanna, P.Chebulagic acid (CA) attenuates LPS-induced inflammation by suppressing NF-κB and MAPK activation in RAW 264.7 macrophagesBiochem. Biophys. Res. Commun.381(1)112-117(2009) 4.Shyni, G.L., Kavitha, S., Indu, S., et al.Chebulagic acid from Terminalia chebula enhances insulin mediated glucose uptake in 3T3-L1 adipocytes via PPARγ signaling pathwayBiofactors40(6)646-657(2014) 5.Lin, L.T., Chen, T.Y., Lin, S.C., et al.Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entryBMC Microbiol.13187(2013)
| Cas No. | 23094-71-5 | SDF | |
| 别名 | 诃子鞣酸 | ||
| Canonical SMILES | OC(CC(C(O[C@H]([C@@H](COC(C1=CC(O)=C2O)=O)O[C@@H]3OC(C4=CC(O)=C(O)C(O)=C4)=O)[C@H](OC(C5=CC(O)=C(O)C(O)=C5C1=C2O)=O)[C@H]3OC6=O)=O)C(C7O)C(C6=CC(O)=C8O)=C8OC7=O)=O | ||
| 分子式 | C41H30O27 | 分子量 | 954.66 |
| 溶解度 | DMSO : 100 mg/mL (104.75 mM) | 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 | 1.0475 mL | 5.2375 mL | 10.4749 mL |
| 5 mM | 0.2095 mL | 1.0475 mL | 2.095 mL |
| 10 mM | 0.1047 mL | 0.5237 mL | 1.0475 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。
Chebulagic acid attenuates HFD/streptozotocin induced impaired glucose metabolism and insulin resistance via up regulations of PPAR 污 and GLUT 4 in type 2 diabetic rats
The aim of the present study was to evaluate the effects of chebulagic acid on enzymes involved in carbohydrate metabolism in high-fat diet/streptozotocin-induced diabetic rats. Diabetes was induced in albino male Wistar rats by feeding them with a high-fat diet comprising of 84.3% standard laboratory rat chow, 5% lard, 10% yolk powder, 0.2% cholesterol, and 5% bile salt for 2 weeks. After 2 weeks, the animals were kept in an overnight fast and injected with a low dose of streptozotocin (35 mg/kg, dissolved in 0.1 M sodium citrate buffer, pH 4.5). At the end of the experimental periods, the blood glucose, plasma insulin, hemoglobin, glycated hemoglobin levels, homeostatic model of insulin resistance, glycogen content, glycogen synthase, glycogen phosphorylase were measured in high-fat diet and streptozotocin-induced diabetic rats whereas the glucose metabolic enzymes such as hexokinase, glucose 6 phosphate dehydrogenase, glucose 6 phosphatase, fructose 1,6 bisphosphatase and protein expression of peroxisome proliferator-activated receptor-污 (PPAR-污) and Glucose transporter 4 (GLUT4) were analyzed. Administration of chebulagic acid to HFD/STZ -induced diabetic rats for 30 days significantly decreased the levels of plasma glucose, homeostatic model assessment of insulin resistance, glycogen phosphorylase and glycosylated hemoglobin and increased the levels of insulin, glycogen content and glycogen synthase. On the other hand, the altered activity of carbohydrate metabolic enzymes, PPAR-污 and GLUT4 were brought back to near-normal levels on treatment with chebulagic acid. The effect produced by chebulagic acid on various parameters was comparable to that of metformin.
Ferroptosis-Inhibitory Difference between Chebulagic Acid and Chebulinic Acid Indicates Beneficial Role of HHDP
The search for a safe and effective inhibitor of ferroptosis, a recently described cell death pathway, has attracted increasing interest from scientists. Two hydrolyzable tannins, chebulagic acid and chebulinic acid, were selected for the study. Their optimized conformations were calculated using computational chemistry at the B3LYP-D3(BJ)/6-31G and B3LYP-D3(BJ)/6-311 + G(d,p) levels. The results suggested that (1) chebulagic acid presented a chair conformation, while chebulinic acid presented a skew-boat conformation; (2) the formation of chebulagic acid requires 762.1729 kcal/mol more molecular energy than chebulinic acid; and (3) the 3,6-HHDP (hexahydroxydiphenoyl) moiety was shown to be in an (R)- absolute stereoconfiguration. Subsequently, the ferroptosis inhibition of both tannins was determined using a erastin-treated bone marrow-derived mesenchymal stem cells (bmMSCs) model and compared to that of ferrostatin-1 (Fer-1). The relative inhibitory levels decreased in the following order: Fer-1 > chebulagic acid > chebulinic acid, as also revealed by the in vitro antioxidant assays. The UHPLC-ESI-Q-TOF-MS analysis suggested that, when treated with 16-(2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxy free radicals, Fer-1 generated dimeric products, whereas the two acids did not. In conclusion, two hydrolyzable tannins, chebulagic acid and chebulinic acid, can act as natural ferroptosis inhibitors. Their ferroptosis inhibition is mediated by regular antioxidant pathways (ROS scavenging and iron chelation), rather than the redox-based catalytic recycling pathway exhibited by Fer-1. Through antioxidant pathways, the HHDP moiety in chebulagic acid enables ferroptosis-inhibitory action of hydrolyzable tannins.
Chebulinic and chebulagic acid binding with serum proteins: biophysical and molecular docking approach
Chebulinic acid (CHN) and chebulagic acid (CHG) have been known for centuries for their anti-cancer, anti-diabetes, HIV and anti-inflammatory properties. In this study, the interaction of these phytochemicals CHN/CHG, with the two major transport proteins for various drugs, human serum albumin (HSA) and 汐-1-acid glycoprotein (AGP), was unraveled by using several spectroscopic techniques and computational methods. The binding of CHN/CHG quenches the HSA/AGP fluorescence intensities, and also these phytochemicals are bound strongly to HSA/AGP proteins. An apparent decrease in fluorescence intensities of CHN/CHG-HSA and CHN/CHG-AGP complex showed the static mode of fluorescence quenching. Furthermore, the intrinsic fluorescence and using site-specific markers ibuprofen competing with these molecules, thereby replacing it in the binding site of subdomain IIIA. The computational methods substantiated the experimental findings, revealing that CHN interacted with Lys414A, Glu492A, Glu492A and Lys413A residues of subdomain IIIA of HSA and for CHG showed the interaction with Lys545A and Lys413A residues of subdomain IIIA of HSA. Fluorescence and surface plasmon resonance data unveiled a previously unreported binding event between CHN/CHG and HSA; the determined binding affinities of both compounds were slightly higher for HSA than AGP. A change in functionality of protein confirmed the esterase-like activity of HSA in the presence of CHG/CHN upon binding with CHG/CHN. Displacement and circular dichroism (CD) experiments analysis showed that the two CHN/CHG and binding specifically to IIIA subdomain on HSA results in the conformational changes in the HSA. Thus, CD revealed a few conformational changes in HSA due to CHN/CHG. The binding of these two phytochemicals to the plasma proteins would give a path to develop new inspired drug molecules for chronic diseases.Communicated by Ramaswamy H. Sarma.
Discovery of chebulagic acid and punicalagin as novel allosteric inhibitors of SARS-CoV-2 3CLpro
The emerging SARS-CoV-2 infection is the cause of the global COVID-19 pandemic. To date, there are limited therapeutic options available to fight this disease. Here we examined the inhibitory abilities of two broad-spectrum antiviral natural products chebulagic acid (CHLA) and punicalagin (PUG) against SARS-CoV-2 viral replication. Both CHLA and PUG reduced virus-induced plaque formation in Vero-E6 monolayer at noncytotoxic concentrations, by targeting the enzymatic activity of viral 3-chymotrypsin-like cysteine protease (3CLpro) as allosteric regulators. Our study demonstrates the potential use of CHLA and PUG as novel COVID-19 therapies.
Pyrogallol, Corilagin and Chebulagic acid target the "fuzzy coat" of alpha-synuclein to inhibit the fibrillization of the protein
The accumulation of the intrinsically disordered protein alpha-synuclein (汐Syn) in the form of insoluble fibrillar aggregates in the central nervous system is linked to a variety of neurodegenerative disorders such as Parkinson's disease, Lewy body dementia, and multiple system atrophy. Here we show that Pyrogallol, Corilagin and Chebulagic acid, compounds containing a different number of catechol rings, are independently capable of delaying and reducing the extent of 汐Syn fibrillization. The efficiency of inhibition was found to correlate with the number of catechol rings. Further, our NMR studies reveal that these compounds interact with the N-terminal region of 汐Syn which is unstructured even in the fibrillar form of the protein and is known as the "fuzzy coat" of fibrils. Thus, Corilagin and Chebulagic acid target the fuzzy coat of 汐Syn and not the amyloid core which is a common target for the inhibition of protein fibrillization. Our results indicate that the N-terminus also plays a key role in the fibrillization of 汐Syn.