Anthraquinone Glucosides Research Articles

Scorch processing of rhubarb (Rheum tanguticum Maxim. ex Balf.) pyrolyzed anthraquinone glucosides into aglycones and improved the therapeutic effects on thromboinflammation via regulating the complement and coagulation cascades pathway

Ethnopharmacological relevanceThe pathophysiological mechanism of thromboinflammation involves the intricate interplay between the inflammatory responses and coagulation cascades. Rhubarb is frequently used in traditional Chinese medicine to treat thromboinflammatory diseases. The scorched rhubarb (prepared by stir-baking the dried raw rhubarb till it partly turns to charcoal) is believed to possess enhanced blood-cooling and stasis-removing functions compared to the raw rhubarb, thereby augmenting the therapeutic effects on thromboinflammation. Aim of the studyThis study aimed to explore the chemical and pharmacological foundations of the scorch processing of rhubarb in order to ensure and enhance the efficacy and safety of the scorched rhubarb for treating thromboinflammatory diseases. Materials and methodsThe dried raw rhubarb pieces were subjected to stir-baking at 180 °C for 10∼80 min to obtain the rhubarbs with varying degrees of scorching. Typical ingredients present in rhubarb pieces and extracts were determined by high-performance liquid chromatography. The therapeutic effects of the raw and scorched rhubarb on thromboinflammation were evaluated using a rat model. Proteomics analysis was employed to screen potential biological pathways associated with thromboinflammation treatment by the raw and scorched rhubarb, which were further verified using a cell model. ResultsMorphological properties indicated that the rhubarb baked at 180 °C for 50 min in this research showed the optimal degree of scorching. Compared to the raw rhubarb, the properly scorched rhubarb exhibited lower levels of anthraquinone glucosides, higher levels of anthraquinone aglycones, superior anti-thromboinflammatory effects, and no purgative side effects. Proteomics analysis revealed that the complement and coagulation cascades pathway played a significant role in mediating the therapeutic effects of the raw and scorched rhubarb on thromboinflammation. Furthermore, it was found that anthraquinone aglycones were more effective than their glucoside counterparts in restoring the impaired vascular endothelial cells as well as regulating the complement and coagulation cascades pathway. ConclusionsProper scorch processing may augment the therapeutic effects of rhubarb on thromboinflammation via relieving inflammation and oxidative stress, repairing vascular endothelial cells, restoring coagulation cascades and blood rheology, and regulating some other biological processes. This may be partly caused by the scorch-induced thermolysis of anthraquinone glucosides into their aglycone counterparts that seemed to perform better in regulating the complement and coagulation cascades pathway.

Anti-Helicobacter pylori Activity of Six Major Compounds Isolated from Rumex acetosa.

Gastric problems are often caused by the well-known Helicobacter pylori (H. pylori) bacterium. One of the biggest obstacles to the treatment of H. pylori infections is increasing the antibiotic resistance. During our search for naturally derived anti-H. pylori compounds, six major compounds were isolated from the methylene chloride (CH2Cl2) and ethyl acetate (EtOAc) fractions of Rumex acetosa that showed anti-H. pylori activity. Three anthraquinones and three anthraquinone glucosides were identified as the major chemical constituents of the CH2Cl2 and EtOAc fractions, respectively. The chemical structures were identified to be emodin (1), chrysophanol (2), physcion (3), emodin-8-O-β-d-glucoside (4), chrysophanol-8-O-β-d-glucoside (5), and physcion-8-O-β-d-glucoside (6) by UV, 1H NMR, 13C NMR, and mass spectrometry. Anti-H. pylori activity, including the minimum inhibitory concentration (MIC) value of each compound, was evaluated against two H. pylori strains. All isolates exhibited anti-H. pylori activity with different potencies, with an MIC value ranging between 3.13 and 25 μM. However, some variations were found between the two strains. While compound 5 displayed the most potent antibacterial activity with an MIC50 value of 8.60 μM and an MIC90 value of 15.7 μM against H. pylori strain 51, compound 1 exhibited the most potent inhibitory activity against H. pylori strain 43504. The two compounds also showed moderate urease inhibitory activity, with compound 1 demonstrating activity higher than that of compound 5. Furthermore, a molecular docking study revealed the high binding ability of compounds 1 and 5 to the active site of H. pylori urease. The present study suggests that the six anthraquinones isolated from R. acetosa with the whole parts of this plant may be natural candidates for the treatment of H. pylori infection. Further studies are required to determine the exact mechanism of action and to evaluate safety issues in the human body.

Phytochemical and Anti-Oxidant Investigation of Alexandrian senna L. Leaves Cultivated in Iraq

Cassia acutifolia, which is commonly known as Alexandrian senna is a medicinal herb belong to family of Leguminosae, The famous use of this herbal shrub is as a laxative act by stimulation intestinal muscles to contract cause the rapid removal of waste matter. Several phytoconstituents present in Senna leaves mostly contain dianthrone glycosides one of anthraquinone derivates. Two crystalline anthraquinone glucosides sennoside A & B have been reported rich in the leaves and pods, in addition to many flavonoids and terpens. this study was designed to investigate the phytochemical component and antioxidant activity of Alexandrian senna L. leaves cultivated in Iraq. this is done by extraction of plant leaves after drying using hexane then ethanol through soxhlet extractor and determine the active ingredient in the leaves extracts using standards chemical test then the antioxindant activity has been evaluated using DPPH scavenging method. The results indicate the presence of important active ingredient such as flavonoids, saponin, carbohydrate, tannin, terpenoid and alkaloids and the leaves extract show a significant anti-oxidant activity at low level with IC50 26.7 as compared with their standard ascorbic acid.

Comparative antibacterial analysis of the anthraquinone compounds based on the AIM theory, molecular docking, and dynamics simulation analysis.

Hydroxyanthraquinones and anthraquinone glucoside derivatives are always considered as the active antibacterial components. Comparison of structure characteristics and antibacterial effect of these compounds was performed by applying quantum chemical calculations, atoms in molecules theory, molecular docking, and dynamics simulation procedure. Density functional theory calculation with B3LYP using 6-31G (d, p) basis set has been used to determine ground state molecular geometries. The molecular geometric stability, electrostatic potential, frontier orbital energies, and topological properties were analyzed at the active site. Once glucose ring is introduced into the hydroxyanthraquinone rings, almost all of the positive molecular potentials are distributed among the hydroxyl hydrogen atoms of the glucose rings. In addition, low electron density ρ (r) and positive Laplacian value of the O-H bond of the anthraquinone glucoside are the evidences of the highly polarized and covalently decreased bonding interactions. The anthraquinone glucoside compounds have generally higher intermolecular binding energies than the corresponding aglycones due to the strong interaction between the glucose rings and the surrounding amino acids. Molecular dynamics simulations further explored the stability and dynamic behavior of the anthraquinone compound and protein complexes through RMSD, RMSF, SASA, and Rg. The type of carboxyl, hydroxyl, and hydroxymethyl groups on phenyl ring and the substituent glucose rings is important to the interactions with the topoisomerase type II enzyme DNA gyrase B.

Chemical Constituents From the Roots of Rubia oncotricha

Phytochemical investigation of the 70% ethanolic extract of the roots of Rubia oncotricha Hand.-Mazz. led to the isolation of 2 new anthraquinone glucosides named 1-hydroxy-2-hydroxymethyl-9,10-anthraquinone-11- O- β-D-glucopyranoside (1) and 1,3,6–trihydroxy-2-hydroxymethyl-9,10-anthraquinone-3- O- β-D-glucopyranoside (2), together with 5 known compounds (3-7). Their structures were elucidated by extensive spectroscopic data analysis (1-dimensional, 2-dimensional-nuclear magnetic resonance, and high resolution-electrospray ionization-mass spectrometry).

Two-dimensional qNMR of anthraquinones in Frangula alnus (Rhamnus frangula) using surrogate standards and delay time adaption

In the absence of adequate reference material, a problem often encountered in natural product chemistry, we investigated the use of surrogate standards in two-dimensional qNMR for the quantification of anthraquinones in the bark of alder buckthorn (Frangula alnus). Using the integrals of cross signals in the HSQC spectrum obtained from commercial standards rutin and duroquinone and adapting the delays for the 1JCH coupling, we quantified the total amount of anthraquinones and anthraquinone glucosides, as well as the content of the value-determining glucofrangulins and frangulins. Thereby, duroquinone was used as an external standard to establish the calibration curve for the methylated anthraquinone scaffold, whereas calibration curves for the glycosides were obtained using the anomeric proton signals of the rutinose disaccharide. The method was validated for accuracy, precision, specificity, linearity and limit of quantitation and shows clear advantages over the method of the European Pharmacopeia, especially in terms of specificity and meaningfulness of the results. Apart from being a useful alternative in the quality control of alder buckthorn, the presented approach demonstrates, moreover, the versatility of sophisticated 2D measurements in quantitative NMR.

In silico screening of anthraquinones from Prismatomeris memecyloides as novel phosphodiesterase type-5 inhibitors (PDE-5Is)

ObjectivePrismatomeris memecyloides Craib (Rubiaceae) is a medicinal plant traditionally used by ethnic minorities in Vietnam for the treatment of erectile dysfunction (ED). The aim of this study was to investigate the chemical compositions and screen in silico its possible inhibitory effect against PDE-5 which reduced cyclic guanosine-3′,5′-monophosphate (cGMP) levels and indirectly caused the male ED. MethodsSeparation of natural compounds were carried out on chromatographic column with silica gel or reversed phase materials, eluting with different solvent gradients. The structures of all isolated compounds were elucidated on the basis of spectroscopic data (HR-MS, 1D/2D-NMR). Docking simulation study of compound (1–7) was performed by using flexible side chains protocol based on Iterated Local Search Global Optimizer Algorithm of AutoDock/Vina v.1.1.2. Pharmacokinetic parameters and toxicity prediction were also calculated by appropriate softwares. ResultsFrom the methanol extract of roots of P. memecyloides collected in Vietnam, seven compounds including four anthraquinone/one anthraquinone glycoside namely damnacanthal (1), lucidin-ω-methyl ether (2), 3-methylalizarin (3), rubiadin-3-methyl ether (4), and 1-O-methylrubiadin 3-O-primeveroside (5) along with two iridoid glucosides, asperulosidic acid (6) and aitchisonide A (7) were isolated. The molecular modeling results showed that 5 anthraquinone compounds possess the lowest binding energies to PDE-5. The anthraquinone glucoside 1-O-methylrubiadin 3-O-primeveroside (5) potentially inhibited PDE-5 similarly to commercial PDE-5Is sildenafil (SLD) and tadalafil (TLD). Calculated pharmacokinetic results like pIC50,pred; miLogP, TPSA, enzyme inhibitory of anthraquinone glucoside (5) were similar and even higher to those of the commercial PDE-5 inhibitors. Especially the predictive toxicity of 1-O-methylrubiadin 3-O-primeveroside (5) was even lower than those of SLD and TLD. ConclusionThis is the first study to find a scientific-based evidence for the ethnic use of P. memecyloides as medicinal plant for the treatment of ED. The result indicates that the anthraquinones (damnacanthal (1), lucidin-ω-methyl ether (2), 3-methylalizarin (3) and rubiadin-3-methyl ether (4)), especially anthraquinone glycoside (1-O-methylrubiadin 3-O-primeveroside (5)) are compounds of potential novel drug class for the ED treatment.

Spiroketalcarminic Acid, a Novel Minor Anthraquinone Pigment in Cochineal Extract Used in Food Additives.

Cochineal extract prepared from the scale insect Dactylopus coccus (American cochineal) has been used as a natural red dye for food, cosmetics, and pharmaceuticals. The major pigment in cochineal extract is carminic acid (CA), an anthraquinone glucoside, and several minor pigments have been previously reported. Our investigation aimed at establishing the safety of cochineal dye products using ultra performance liquid chromatography-photo diode array-electrospray ionization-time of flight (UPLC-PDA-ESI-TOF)/MS found an unknown minor pigment, spiroketalcarminic acid (1), in three commercial cochineal extract samples; cochineal extract used in food additives, carmine that is an aluminum salt of cochineal extract used as natural dye, and a research reagent of CA. The purification of 1 from cochineal extract involved sequential chromatographic techniques, including preparative reversed-phase HPLC. Two dimensional (2D)-NMR and mass analyses established the structure of 1 to be a novel anthraquinone with an unusual 6,5-spiroketal system instead of the C-glucosyl moiety of CA. The absolute stereochemistry of the spiroketal moiety in 1 was determined by nuclear Overhauser effect spectroscopy (NOESY) correlations and optical rotation. No data corresponding to 1 had previously been reported for extracts of dried cochineal insects and traditional art products dyed with cochineal extract, indicating that 1 is likely produced during the preparation of commercial cochineal extract.

Potent bacterial neuraminidase inhibitors, anthraquinone glucosides from Polygonum cuspidatum and their inhibitory mechanism

Ethnopharmacological relevanceP. cuspidatum is a popular Chinese medicinal herb, having a long history of usage in traditional Chinese medicine for the treatment of several inflammatory diseases in the form of powders and decoctions. Similarly there are many reports that P. cuspidatum has antibacterial and anti-inflammatory effects, both of which are properties associated with compounds having activity against bacterial neuraminidase (BNA). Aim of the studyWe investigated whether P. cuspidatum's metabolites exhibited BNA inhibition. Consistent with our hypothesis, we found several inhibitors from the methanol extract of this plant, and then fully characterized their inhibitory mechanisms. Materials and methodsActivity guided separation of methanol extract led to isolation of individual constituents, and subsequently their structures were elucidated by spectroscopic analysis. Detailed kinetic behaviors of BNA inhibitors were explored by showing the changes of Km and Vmax, the ratios of KI/KIS and Kik/Kiv, and fluorescence quenching effect. Results and conclusionThis study attempted to isolate the responsible metabolites and elucidate the BNA inhibitory mechanism. The principal BNA inhibitory compounds (2–6) were identified as emodin (2), physcion-8-O-β-D-glucopyranoside (3), emodin-8-O-β-D-glucopyranoside (4), emodin-1-O-β-D-glucopyranoside (5), and 2-methoxy-6-acetyl-7-methyljuglone (6). Unexpectedly, anthraquinone glucosides (3–5) were much more potent than their corresponding aglycones (1 and 2). For example, emodin (2) had an IC50=5.4μM, whereas its glucosides (4 and 5) had IC50=0.85μM and 0.43μM respectively. A similar trend was observed with physcion (1, IC50>200μM) and its glucoside (3, IC50=6.2μM). The anthraquinone (2) was mixed type I inhibitor, whereas its glucosides (4 and 5) were noncompetitive. In addition, the fluorescence quenching study showed that the affinity constants (KSV) of inhibitors increased in proportion to their inhibitory potencies. Furthermore, we quantified the major and minor metabolites through UPLC-PDA-Q-TOF/MS, and revealed that the most potent inhibitors were the major constituents. This result contributes to our understanding of P. cuspidatum utility as functional food stuff and widely used herbal medicine.

Differential response of terpenes and anthraquinones derivatives in Rumex dentatus and Lavandula officinalis to harsh winters across north-western Himalaya

Herbs adapted to diverse climates exhibit distinct variability to fluctuating temperatures and demonstrate various metabolic and physiological adaptations to harsh environments. In this research, Rumex dentatus L. and Lavandula officinalis L. were collected before snowfall in September–November to evaluate variability in major phytoconstituents to diverse seasonal regime. LC-MS was used for simultaneous determination of eight anthraquinone derivatives in R. dentatus, i.e. emodin, physcion, chrysophanol, physcion glucoside, endocrocin, emodin glucoside, chrysophanol glucoside and chromone derivatives and monoterpenes in L. officinalis i.e. (Z)-β-ocimene, (E)-β-ocimene, terpene alcohol, terpin-4-ol, acetate ester-linalyl acetate and bicyclic sesquiterpene (E)-caryophyllene. The correlation analysis confirmed significant variation in anthraquinone glucoside and terpene content within Rumex and Lavender, respectively, and altitude was established as the determinant factor in secondary metabolism of both herbs. The study concludes the propagation of herbs in bioclimatic belts which favour accumulation of major constituents and validate their greater pharmacological activity.

Composition and Bioactivities of Leaf Essential Oil of Cassia tora

L., an oriental herbnative to south Asia, grows as a weed in the rainy season and can grow 1–2 m in height [2]. It is traditionally used in thetreatment of jaundice [3], ringworm [4], constipation, and leprosy [5].Previous phytochemical investigation has found that it is a rich source of anthraquinone glucosides [6, 7]. Only theseed essential oil composition has been reported from China [8]. The biological activities and composition of the leaf essentia loil have not been previously reported.The essential oil from the leaf of

Anthraquinones and stilbenes from the roots and rhizomes of Rhubarb

Two new anthraquinone glucosides [aloe-emodin 8-O-β-d-(6′-galloyl)glucopyranoside (1) and rhein 8-O-β-d-(6′-galloyl)glucopyranoside (2)], together with 16 known compounds (3–18), were isolated from the roots and rhizomes of Rheum hotaoense C.Y. Cheng et C.T. Kao. Their structures were elucidated on the basis of extensive investigation of 1D and 2D NMR, HR-ESI-MS, and chemical evidence. In addition, the free-radical-scavenging activity was tested using the 1,1-diphenyl-2-picrylhydrazyl assay.

Analysis of Rhizoma Polygoni Cuspidati by HPLC and HPLC‐ESI/MS

An HPLC method with photodiode array detection (PAD) and ESI/MS detection was developed for the qualitative and quantitative analysis of the major chemical constituents of the dried rhizome of Polygonum cuspidatum Sieb. et Zucc. (Rhizoma Polygoni Cuspidati; Chinese name Hu-Zhang). Based on the chromatographic separation on an Altima C(18) column using 0.5% aqueous acetic acid and acetonitrile as the mobile phase, nine compounds, including stilbenes, stilbene glucosides, anthraquinones and anthraquinone glucosides, were identified by online ESI/MS analysis and seven were quantified by HPLC-PAD. A full validation of the method including sensitivity, linearity, repeatability and recovery was conducted. Linear calibration was achieved over the concentration range 1-200 mg/L with R(2) > 0.999, whilst the limits of detection ranged from 0.51 to 1.57 ng. Repeatability was evaluated by intra- and inter-day assays and the RSD value was within 1.79%. Recoveries of the quantified compounds were within the range 96.0-100.1% with RSD values of less than 2.2%. Five samples of Rhizoma Polygoni Cuspidati from different regions were analysed using the developed method. The major constituents piceid, resveratrol, emodin-8-O-beta-D-glucoside and emodin were selected to provide an index for the quality assessment of the herbal drug.

Identification and determination of the major constituents in traditional Chinese medicinal plant Polygonum multiflorum thunb by HPLC coupled with PAD and ESI/MS

An HPLC-PAD-MS method has been developed for the qualitative and quantitative analysis of the major chemical constituents in Polygonum multiflorum Thunb. Chromatographic separation was conducted on an Alltima C18 column using water:acetonitrile:acetic acid as the mobile phase. Altogether nine compounds of various classes, including stilbene glucosides, anthraquinone glucosides and anthraquinone derivates, were identified by online ESI/MS. Their identities were ascertained by comparison with data derived from the literature and/or standard compounds. Five components were quantified by HPLC-PAD and the method was fully validated. All the linear regressions were acquired with R2 > 0.99 and the quantification limits (with a signal-to-noise ratio of 3) ranged from 0.63 and 1.57 ng. Repeatability was evaluated by intra- and inter-day assays and RSD value was within 2.47%. Recovery studies for the quantified compounds were found to be within the range 96.32-102.53% with RSD less than 2.35%. The overall procedure is rapid and reproducible and is considered suitable for qualitative and quantitative analysis of a large number of samples.

Comparative Study of Chemical Constituents of Rhubarb from Different Origins

A comparative study of the pharmacologically active constituents of 24 rhubarb samples, which were identified genetically as Rheum tanguticum, 3 intraspecies groups of R. palmatum and R. officinale, was conducted using reversed-phase high performance liquid chromatography (HPLC) methods. Thirty compounds belonging to anthraquinones, anthraquinone glucosides, dianthrones, phenylbutanones, stilbenes, flavan-3-ols, procyanidins, galloylglucoses, acylglucoses, gallic acid, and polymeric procyanidins were analyzed quantitatively. The drug samples derived from the same botanical source showed similar chromatographic profiles, and the comparable specific shape that appeared in the 10-directed radar graphs constructed on the basis of the results of quantitative analysis indicated the relationship between chemical constituent patterns and genetic varieties of rhubarb samples.

Reinvestigation of the Chemical Constituents of Eurycoma Longifolia

A preliminary screening demonstrated that the ethanolic extract of Eurycoma longifolia could decrease the basal level but increase the human chorionic gonadotropin (hCG)-induced production of testosterone by rat Leydig cells. Thirteen known compounds including five canthin-6-one alkaloids, three anthraquinones and five anthraquinone glucosides were isolated from the roots of E.longifolia. The structures of these compounds were established by spectroscopic analysis and comparison with literature data.

Antioxidant constituents from rhubarb: structural requirements of stilbenes for the activity and structures of two new anthraquinone glucosides

The methanolic extracts from five kinds of rhubarb were found to show scavenging activity for DPPH radical and O 2 −. Two new anthraquinone glucosides were isolated from the rhizome of Rheum undulatum L. together with two anthraquinone glucosides, a naphthalene glucoside, and 10 stilbenes. In the screening test for radical scavenging activity of rhubarb constituents, stilbenes and a naphthalene glucoside showed activity, but anthraquinones and sennosides did not. In addition, most stilbenes inhibited lipid peroxidation of erythrocyte membrane by tert-butyl hydroperoxide. Detailed examination of the scavenging effect on various related compounds suggested the following structural requirements; 1) phenolic hydroxyl groups are essential to show the activity; 2) galloyl moiety enhances the activity; 3) glucoside moiety reduces the activity; 4) dihydrostilbene derivatives maintain the scavenging activity for the DPPH radical, but they show weak activity for O 2 −. In addition, several stilbenes with both the 3-hydroxyl and 4′-methoxyl groups inhibited xanthine oxidase.

Effects of stilbene constituents from rhubarb on nitric oxide production in lipopolysaccharide-activated macrophages

Two new anthraquinone glucosides [chrysophanol 8-O-β-d-(6′-galloyl)-glucopyranoside, aloe-emodin 1-O-β-d-glucopyranoside] together with various known stilbenes and their glucosides, anthraquinone glucosides, and a naphthalene glucoside were isolated from the rhizome of Rheum undulatum L. Three stilbenes (rhapontigenin, piceatannol, resveratrol), a naphthalene glucoside (torachrysone 8-O-β-d-glucopyranoside), and two stilbene glucoside gallates (rhaponticin 2′′-O-gallate, rhaponticin 6′′-O-gallate) showed inhibitory activity of NO production in lipopolysaccharide-activated macrophages. (IC50=11–69 μM). The oxygen functions (-OH,-OCH3) at the benzene ring were found to be essential to show the activity. Whereas, the glucoside moiety reduced the activity, while the α,β-double bond did not affect the activity. Furthermore, the active stilbenes (rhapontigenin, piceatannol, resveratrol) inhibited iNOS induction.

Alaternin glucoside isomer from cassia tora

From the seeds of Cassia tora, an anthraquinone glucoside was isolated and characterized as alaternin 2-O- β- d-glucopyranoside.

Anthraquinone ß-D-glucoside from Cassia grandis

A new anthraquinone glucoside has been isolated from the pods of Cassia grandis and was identified as 1,3,4-trihydroxy-6,7,8-trimethoxy-2-methyl anthraquinone-3-O-s-D-glucopyranoside. The structure of this glucoside was elucidated by chemical and spectroscopic methods and confirmed by synthesis.