chebulagic-acid and chebulinic-acid

Ellagitannins are literally a class of tannins. Triggered by the oxidation of the phenolic parts on β-pentagalloyl-d-glucose, ellagitannins are generated through various structural conversions, such as the coupling of the phenolic parts, oxidation to highly complex structures, and the formation of dimer and lager analogs, which expand the structural diversity. To date, more than 1000 natural ellagitannins have been identified. Since these phenolic compounds exhibit a variety of biological activities, ellagitannins have potential applications in medicine and health enhancement. Within the context of identifying suitable applications, considerations need to be based on correct structural features. This review describes the structural revisions of 32 natural ellagitannins, namely alnusiin; alnusnin A and B; castalagin; castalin; casuarinin; cercidinin A and B; chebulagic acid; chebulinic acid; corilagin; geraniin; isoterchebin; nobotanin B, C, E, G, H, I, J, and K; punicalagin; punicalin; punigluconin; roxbin B; sanguiin H-2, H-3, and H-6; stachyurin; terchebin; vescalagin; and vescalin. The major focus is on the outline of the initial structural determination, on the processes to find the errors in the structure, and on the methods for the revision of the structure.

Topics: Benzopyrans; Glucosides; Hydrolyzable Tannins; Molecular Structure; Oxidation-Reduction; Phenols; Terminology as Topic

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 (

Topics: Animals; Antioxidants; Benzopyrans; Cells, Cultured; Ferroptosis; Glucosides; Hydrolyzable Tannins; Mesenchymal Stem Cells; Models, Molecular; Rats, Sprague-Dawley

Diabetic retinopathy (DR) is characterized by pro-inflammatory, pro-angiogenic and pro-fibrotic environment during the various stages of the disease progression. Basement membrane changes in the retina and formation of fibrovascular membrane are characteristically seen in DR. In the present study the effect of Alcoholic (AlE) extracts of Triphala an ayurvedic herbal formulation and its chief compounds, Chebulagic (CA), Chebulinic (CI) and Gallic acid (GA) were evaluated for TGFβ1-induced anti-fibrotic activity in choroid-retinal endothelial cells (RF/6A).. RF/6A cells were treated with TGFβ1 alone or co-treated with AlE, CA, CI or GA. The mRNA and protein expression of fibrotic markers (αSMA, CTGF) were assessed by qPCR and western blot/ELISA. Functional changes were assessed using proliferation assay and migration assay. To deduce the mechanism of action, downstream signaling was assessed by western blot analysis along with in silico docking studies.. AlE (50 μg/ml) CA and CI at 10 μM reduced the expression of pro-fibrotic genes (αSMA and CTGF) induced by TGFβ1, by inhibiting ERK phosphorylation. GA did not inhibit TGFβ1 mediated changes in RF/6A cells. In silico experiments shows that CA and CI has favourable binding energy to bind with TGFβ receptor and inhibit the downstream signaling, while GA did not.. Hence this study identifies Triphala and its chief compounds CA and CI as potential adjuvants in the management of DR.

Topics: Animals; Benzopyrans; Binding Sites; Cell Movement; Cell Proliferation; Cells, Cultured; Choroid; Diabetic Retinopathy; Endothelial Cells; Extracellular Signal-Regulated MAP Kinases; Fibrosis; Glucosides; Hydrolyzable Tannins; Macaca mulatta; Molecular Docking Simulation; Neovascularization, Pathologic; Phosphorylation; Plant Extracts; Protein Binding; Receptors, Transforming Growth Factor beta; Retinal Vessels; Signal Transduction; Transforming Growth Factor beta1

Topics: Animals; Benzopyrans; Chromatography, Liquid; Drug Stability; Glucosides; Hydrolyzable Tannins; Linear Models; Male; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry; Tissue Distribution

Tumor necrosis factor-α (TNFα) a pleiotropic cytokine induces pro-inflammatory and pro-angiogenic changes in conditions such as diabetic retinopathy (DR) and neovascular age related macular degeneration (NV-AMD). Hence, inhibition of TNFα mediated changes can benefit the management of DR and NV-AMD. Triphala, an ayurvedic herbal preparation is known to have immunomodulatry functions. In this study we evaluated the alcoholic extract of triphala (AlE) and its compounds Chebulagic acid (CA), Chebulinic acid (CI) and Gallic acid (GA) for their anti-TNFα activity. TNFα induced pro-inflammatory and pro-angiogenic changes in the retinal-choroid microvascular endothelial cells (RF/6A). Treatment with CA/CI/GA and the whole Triphala extract showed characteristic inhibition of MMP-9, cell proliferation/migration and tube formation as well the expression of IL-6, IL-8 and MCP-1 without affecting cell viability. This was mediated by inhibition of p38, ERK and NFκB phosphorylation. Ex vivo angiogenesis assay using chick chorioallantoic membrane (CAM) model also showed that TNFα-induced angiogenesis and it was inhibited by AlE and its active principles. Further, in silico studies revealed that CA, CI and GA are capable of binding the TNFα-receptor-1 to mediate anti-TNFα activity. This study explains the immunomodulatory function of Triphala, evaluated in the context of retinal and choroid vasculopathies in vitro and ex vivo; which showed that CA, CI and GA can be a potential pharmacological agents in the management of DR and NV-AMD.

Topics: Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents; Benzopyrans; Cell Line; Chick Embryo; Dose-Response Relationship, Drug; Endothelial Cells; Extracellular Signal-Regulated MAP Kinases; Gallic Acid; Glucosides; Hydrolyzable Tannins; Inflammation Mediators; Macaca mulatta; Matrix Metalloproteinase 9; Molecular Docking Simulation; Neovascularization, Physiologic; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Plant Extracts; Protein Binding; Receptors, Tumor Necrosis Factor, Type I; Retinal Neovascularization; Retinal Vessels; Signal Transduction; Time Factors; Tumor Necrosis Factor-alpha

Epithelial to Mesenchymal Transition (EMT) of the retinal pigment epithelium is involved in the pathogenesis of proliferative vitreoretinopathy (PVR) that often leads to retinal detachment. In this study, Triphala, an ayurvedic formulation and two of its active ingredients, namely chebulagic acid and chebulinic acid were evaluated for anti-EMT properties based on in vitro experiments in human retinal pigment epithelial cell line (ARPE-19) under TGFβ1 induced conditions. ARPE-19 cells were treated with TGFβ1 alone or co-treated with various concentrations of aqueous extract (AqE) (30-300 μg/ml); alcoholic extract (AlE) (50-500 μg/ml) of triphala and the active principles chebulagic acid (CA) and chebulinic acid (CI) (CA,CI: 50-200 μM). The expression of EMT markers namely MMP-2, αSMA, vimentin and the tight junction protein ZO-1 were evaluated by qPCR, western blot and immunofluorescence. The functional implications of EMT, namely migration and proliferation of cells were assessed by proliferation assay, scratch assay and transwell migration assay. AqE, AlE, CA and CI reduced the expression and activity of MMP-2 at an ED50 value of 100 μg/ml, 50 μg/ml, 100 μM and 100 μM, respectively. At these concentrations, a significant down-regulation of the expression of αSMA, vimentin and up-regulation of the expression of ZO-1 altered by TGFβ1 were observed. These concentrations also inhibited proliferation and migration of ARPE-19 cells induced by TGFβ1. EMT was found to be induced in ARPE-19 cells, through SMAD-3 phosphorylation and it was inhibited by AqE, AlE, CA and CI. Further studies in experimental animals are required to attribute therapeutic potential of these extracts and their active compounds, as an adjuvant therapy in the disease management of PVR.

Topics: Benzopyrans; Cell Line; Epithelial Cells; Epithelial-Mesenchymal Transition; Glucosides; Humans; Hydrolyzable Tannins; Phosphorylation; Plant Extracts; Retinal Pigment Epithelium; Smad3 Protein

Persistent activation of hepatic stellate cells (HSC-T6) has been known to cause liver fibrosis. In this study, our objective was to investigate the effects of chebulagic acid and chebulinic acid, two hydrolysable tannins of tropical almond (Terminalia chebula) fruits, on collagen synthesis and signal transduction in transforming growth factor-β1-stimulated HSC-T6 cells. The expression of Smad2, Smad3, Smad4, collagen I(α1)/III, and plasminogen activator inhibitor 1 (PAI-1) mRNAs was determined by reverse-transcription polymerase chain reaction and their protein levels were assessed by western blotting.. Results showed that chebulagic acid and chebulinic acid at 20 µmol L(-1) exhibited cytotoxic and anti-proliferative effects on HSC-T6 cells. They also significantly decreased the expression of Smd2, Smad3 and Smad4, and the synthesis of collagen, procollagen I (α1) and III, as well as suppressing the activation of PAI-1; these events consequently facilitated the resolution of fibrosis.. These results indicate that both chebulagic acid and chebulinic acid possess antifibrotic activity, and their mechanism of action could be through the inhibition of the Smad pathway.

Topics: Animals; Benzopyrans; Blotting, Western; Cell Proliferation; Cells, Cultured; Collagen; Collagen Type I; Collagen Type III; Cytotoxins; Fruit; Glucosides; Hepatic Stellate Cells; Hydrolyzable Tannins; Liver Cirrhosis; Phytotherapy; Plant Extracts; Plasminogen Activator Inhibitor 1; Rats; RNA, Messenger; Signal Transduction; Smad Proteins, Receptor-Regulated; Terminalia; Transforming Growth Factor beta1

Abhayarishta is an Ayurvedic formulation prepared traditionally by the fermentation of the decoction of Terminalia chebula (pericarp), Vitis vinifera (fruits), Embelia ribes (fruits) and Madhuca indica (flowers). In the present communication, chemical changes occurring during fermentation in Abhayarishta have been studied for the purpose of its standardization. An HPLC-DAD method for quantitative estimation of selected marker constituents in the formulation has been developed and validated. A comparison of decoction and final processed formulation revealed that major polyphenolics (chebulagic and chebulinic acid) of T. chebula were hydrolyzed to their respective monomers and, consequently, there was an increase in the amount of chebulic acid, gallic acid, ellagic acid and ethyl gallate after fermentation. 5-Hydroxymethyl furfural (5-HMF) was also found in the formulation. Thus, emphasis is laid upon consideration of processing methods of formulation which has been lacking in the standardization of most of Ayurvedic formulations.

Topics: Benzopyrans; Chromatography, High Pressure Liquid; Ellagic Acid; Fermentation; Furaldehyde; Gallic Acid; Glucosides; Hydrolyzable Tannins; Medicine, Ayurvedic; Plant Extracts; Reproducibility of Results

The aqueous extract of galls from Terminalia chebula Retz. (Combretaceae) was fractionated on Diaion and refractionated on octadecyl silica column. Six phenolic compounds were isolated and identified as gallic acid (1), punicalagin (2), isoterchebulin (3), 1,3,6-tri-O-galloyl-β-D-glucopyranose (4), chebulagic acid (5) and chebulinic acid (6). All of the compounds showed stronger 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and melanin inhibitory activities than ascorbic acid, butylated hydroxytoluene, α-tocopherol, arbutin and kojic acid, the reference compounds. Gallic acid (1) exhibited inhibitory activity against nitric oxide production in lipopolysaccharide-activated macrophages. However, all isolated compounds exhibited less activity than the reference compounds in mushroom tyrosinase inhibition and human tumour cytotoxicity assays. This study has demonstrated that the phenolic compounds isolated from galls of T. chebula might contribute significantly due to their antioxidant and whitening activities.

Topics: Analysis of Variance; Animals; Benzopyrans; Biphenyl Compounds; Cell Line, Tumor; Cell Proliferation; Chemical Fractionation; Free Radical Scavengers; Gallic Acid; Glucosides; Humans; Hydrolyzable Tannins; Melanins; Mice; Molecular Structure; Nitric Oxide; Phenols; Picrates; Plant Extracts; Plant Tumors; Terminalia

As a chromatographic column, the high-speed counter-current chromatography system was equipped with a preparative HPLC series, enabling the successful isolation of hydrolysable tannins from the fruits of Terminalia chebula, a traditional Chinese medicine. The two-phase solvent system was composed of n-hexane-ethyl acetate-methanol-water (1:20:1:20 v/v). As a result, 33.2 mg chebulagic and 15.8 mg chebulinic acids were obtained in one step from 300 mg of crude extract. Their purities were determined by HPLC to be 95.3 and 96.1%, respectively. The chemical structures were identified by their MS and 1H NMR spectra.

Topics: Benzopyrans; Chromatography, High Pressure Liquid; Countercurrent Distribution; Drugs, Chinese Herbal; Glucosides; Hydrolyzable Tannins; Magnetic Resonance Spectroscopy; Molecular Structure; Solvents; Spectrometry, Mass, Fast Atom Bombardment; Terminalia

We used the agar dilution method to evaluate the antibacterial effect of Terminalia macroptera leaf (Tml) extract against nine reference and clinical Neisseria gonorrhoeae strains, including penicillin- and tetracycline-resistant and -susceptible strains. Tml possesses anti-N. gonorrhoeae activity against all of the strains and the minimum inhibitory concentrations (MIC) were between 100 and 200 microg ml(-1). We then used a liquid-liquid partition method to divide the Tml extract into five fractions and determined the anti-N. gonorrhoeae activity of each of the fractions. All of the fractions showed antibacterial activity. The most active one was identified as the diethyl ether fraction and had MIC values of between 25 and 50 microg ml(-1) against all of the strains.

Topics: Anti-Bacterial Agents; Benzopyrans; Ellagic Acid; Flavonoids; Gallic Acid; Glucosides; Hydrolyzable Tannins; Luteolin; Neisseria gonorrhoeae; Plant Extracts; Plant Leaves; Tannins; Terminalia

To analyze the hydrolyzable tannins-chebulinic acid (I) and chebulagic acid(II) in Fructus Chebulae and its confusion varieties by using high performance capillary electrophoresis (HPCE) method.. Using a capillary (375 microns OD x 50 microns ID; 81.5 cm x 61.5 cm) and a power supply set at 24 kV, with phosphate-borate buffer containing 20 mmol.L-1 Na2HPO4-60 mmol.L-1 boric acid and a UV detector at 280 nm, sample solution was loaded in decompression mode at the positive end of the capillary, the loading time was 5 s.. The linear ranges of I and II were 0.0842-0.842 and 0.842 and 0.0940-0.940 mg.mL-1 respectively, the correlation coefficient were 0.9966 and 0.9957, the average recoveries were 95.6% (RSD = 4.0%, n = 5) and 95.0% (RSD = 4.4%, n = 5), the RSDs (n = 5) of measurement precision test were 2.2% and 1.7%, the RSDs (n = 6) of reproduction test were 5.4% and 4.0% respectively. The contents of I and II were obviously interrelated with the variety and characteristics of Fructus Chebulae, the contents of I and II in the confusion varieties of Fructus Chebulae were very low.. It is suitable to use I and II as the criterion in quality evaluation of Fructus Chebulae, and the HPCE method is effective for quality evaluation of the crude Fructus Chebulae.

Topics: Benzopyrans; Drug Contamination; Electrophoresis, Capillary; Fruit; Glucosides; Hydrolyzable Tannins; Plants, Medicinal; Quality Control; Tannins; Terminalia

Three hydrolyzable tannins chebulinic acid (I), chebulagic acid(II) and 1,3, 6-tri-O-galloyl-beta-D-glucose (III) in Fructus Chebulae from different habitats were determined by RP-HPLC method. The contents of I and II were obviously interrelated with the variety and characteristics of Fructus Chebulae. It's suitable to use I and II as indexes in quality evaluation of the crude drug of Fructus Chebulae.

Topics: Benzopyrans; Fruit; Glucosides; Hydrolyzable Tannins; Plants, Medicinal; Quality Control; Species Specificity; Tannins; Terminalia