Anthraquinones Rhein Research Articles

Reducing the water quenching processes using heavy water in capillary electrophoresis with fluorescence detection

Water, ubiquitous in analytical methods, is renowned for its fluorescence quenching properties, influencing techniques like fluorescence spectrophotometry or techniques with fluorescence detection. This study explores the impact of water (H₂O) substitution for heavy water (D₂O) on the fluorescence behavior of anthraquinones and anthracyclines. Anthraquinones and anthracyclines play crucial roles in pharmacy, serving as essential components in various therapeutic formulations, particularly in cancer treatment and other pharmacological interventions. Capillary electrophoresis (CE) with heavy water as the background electrolyte (BGE) solvent offers superior sensitivity to the separation and detection of these analytes. Experimental results demonstrate the improved detection limits and separation efficiency of selected anthraquinones rhein (RH), aloe-emodin (AE), and anthracyclines doxorubicin (DOX), epirubicin (EPI) and daunorubicine (DAU) in heavy water-based buffers, highlighting the potential of heavy water in advancing analytical chemistry.

Rhein ameliorates transverse aortic constriction-induced cardiac hypertrophy via regulating STAT3 and p38 MAPK signaling pathways.

The progression from compensatory hypertrophy to heart failure is difficult to reverse, in part due to extracellular matrix fibrosis and continuous activation of abnormal signaling pathways. Although the anthraquinone rhein has been examined for its many biological properties, it is not clear whether it has therapeutic value in the treatment of cardiac hypertrophy and heart failure. In this study, we report for the first time that rhein can ameliorate transverse aortic constriction (TAC)-induced cardiac hypertrophy and other cardiac damage in vivo and in vitro. In addition, rhein can reduce cardiac hypertrophy by attenuating atrial natriuretic peptide, brain natriuretic peptide, and β-MHC expression; cardiac fibrosis; and ERK phosphorylation and transport into the nucleus. Furthermore, the inhibitory effect of rhein on myocardial hypertrophy was similar to that of specific inhibitors of STAT3 and ERK signaling. In addition, rhein at therapeutic doses had no significant adverse effects or toxicity on liver and kidney function. We conclude that rhein reduces TAC-induced cardiac hypertrophy via targeted inhibition of the molecular function of ERK and downregulates STAT3 and p38 MAPK signaling. Therefore, rhein might be a novel and effective agent for treating cardiac hypertrophy and other cardiovascular diseases.

Antimicrobial Activity of Eucalyptus globulus, Azadirachta indica, Glycyrrhiza glabra, Rheum palmatum Extracts and Rhein against Porphyromonas gingivalis.

Novel plant-derived antimicrobials are of interest in dentistry, especially in the treatment of periodontitis, since the use of established substances is associated with side effects and concerns of antimicrobial resistance have been raised. Thus, the present study was performed to quantify the antimicrobial efficacy of crude plant extracts against Porphyromonas gingivalis, a pathogen associated with periodontitis. The minimal inhibitory concentrations (MICs) of Eucalyptus globulus leaf, Azadirachta indica leaf, Glycyrrhiza glabra root and Rheum palmatum root extracts were determined by broth microdilution for P. gingivalis ATCC 33277 according to CLSI (Clinical and Laboratory Standards Institute). The MICs for the E. globulus, A. indica and G. glabra extracts ranged from 64 mg/L to 1024 mg/L. The lowest MIC was determined for an ethanolic R. palmatum extract with 4 mg/L. The MIC for the anthraquinone rhein was also measured, as the antimicrobial activity of P. palmatum root extracts can be partially traced back to rhein. Rhein showed a remarkably low MIC of 0.125 mg/L. However, the major compounds of the R. palmatum root extract were not further separated and purified. In conclusion, R. palmatum root extracts should be further studied for the treatment of periodontitis.

Long-Term Administration of Anthraquinone Rhein on Induction of Constipation in Sprague-Dawley Rats via SCF/c-Kit Signaling Pathways

Background and Study Aims. It has been shown that abuse of laxatives is becoming a serious problem; therefore, a comprehensive understanding of its effect and possible mechanism on colon motility is essential to select effective treatments and avoid their abuse. Herein, we aimed to investigate the long-term stimulation of rhein on induction of constipation in rats and its underlying mechanisms. Materials and Methods. After establishing rat models of constipation, the rats were randomly divided into two equal subgroups and administered daily with normal saline (model control group) or 10 ml/kg PEG4,000 (PEG-treated group). Simultaneously, normal Sprague-Dawley (SD) rats were administered with normal saline (normal group). Physiological and fecal parameters were calculated, and intestinal transmission function was evaluated. After scarification, colonic tissues were freshly prepared for histological localization detected by immunohistochemical analysis and for the expression of stem cell factor (SCF) and c-kit proteins determined by western blot assay. Results. Following the initiation of rhein-induced rat constipation, body weight was lost slightly, the first time of black stool discharge was obviously longer, and the fecal moisture and number of fecal pellets decreased distinctly as compared with normal group. A decreased expression of SCF and c-kit was detected in model control group in comparison with normal group. Notably, compared with model control group, neither the alterations of fecal parameters and intestinal transmission function were effectively restored, nor the expression of SCF and c-kit was markedly elevated after administration of PEG4,000 for 30 d. Conclusion. Long-term stimulation of rhein can develop the constipation via SCF/c-kit signaling pathway, yet the symptoms of constipation and colon power cannot be alleviated or restored by PEG4,000. Collectively, these findings strongly suggest that long-term use of anthraquinone laxatives should be avoided for clinical treatment of constipation.

Anti-amebic effects of Chinese rhubarb (Rheum palmatum) leaves' extract, the anthraquinone rhein and related compounds

Entamoeba histolytica infects 50 million people worldwide and causes 55 thousand fatalities every year. Current anti-amebic drugs (e.g. paromomycin) work either at the level of the intestinal lumen (where trophozoites proliferate via cell divisions) or on the invasive trophozoites that have penetrated the gut or colonized internal organs (e.g. metronidazole). Some of these drugs are highly toxic to patients, have generated trophozoite resistance, or caused mutations and cancer in laboratory animals. Thus, alternative anti-amebic compounds need to be identified to minimize the side effects (on patients) or resistance (by amebas) to current treatments. The literature suggests that anthraquinones (chemicals found in medicinal plants) have antibacterial, antiparasitic, anti-inflammatory and antioxidant properties. Here we provide experimental evidence that Chinese rhubarb (Rheum palmatum) leaves' extract (rich in the anthraquinone rhein) inhibits E. histolytica trophozoite growth in vitro. In addition, from a set of ten isolated/synthetic anthraquinones (which we suspected to have anti-amebic properties), four analogs (rhein; AHHDAC = 1-amino-4-hydroxy-9, 10-dioxo-9, 10-dihydro-anthracene-2-carboxylic acid; unisol blue AS; and sennoside B) efficiently inhibited amebic growth at EIC50 concentrations comparable to metronidazole. The mechanism of action of these compounds still needs to be determined, although anthraquinones might enhance the production of toxic oxygen metabolites as it has been suggested for various protists (e.g. Leishmania, Plasmodium, Trypanosoma). Our research is the first to explore anti-amebic effects of Chinese rhubarb leaves' extract and isolated/synthetic anthraquinones on pathogenic Entamoeba.

The anthraquinone rhein exhibits synergistic antibacterial activity in association with metronidazole or natural compounds and attenuates virulence gene expression in Porphyromonas gingivalis

ObjectiveRhein is a major anthraquinone found in rhubarb root. As a continuation of our ongoing studies aimed to identify beneficial properties of this anthraquinone for periodontal disease, in this study, we investigated the ability of rhein to (i) exhibit antibacterial synergy towards the periodontopathogen Porphyromonas gingivalis when used in combination with metronidazole or polyphenols belonging to different families, and (ii) attenuate virulence factor gene expression in P. gingivalis. MethodsThe minimal inhibitory concentrations (MIC) of compounds under investigation were determined by a broth microdilution assay. The synergistic effects of rhein in association with either metronidazole or polyphenols of various families were evaluated using the chequerboard technique to determine the fractional inhibitory concentration index (FICI). The effect of rhein on virulence factor gene expression in P. gingivalis was determined by quantitative RT-PCR. ResultsRhein showed a MIC of 2.5μg/mL, which was similar to that of metronidazole. Except for the association with epigallocatechin-3-gallate that gave an additive effect, all the other combinations (licochalcone A, glabridin, myricetin, and metronidazole) resulted in synergistic effects. The strongest synergy was observed when rhein was used in association with myricetin (FICI=0.12) and licochalcone A (FICI=0.19). At a sub-MIC of rhein (0.5μg/mL), a significant decrease in the expression of fimA, hagA, and hagB genes, which are involved in host colonization, was observed. Moreover, the expression of rgpA and kgp, two protease genes related to inactivation of host defense mechanisms, tissue destruction, and nutrient acquisition, was also down-regulated. ConclusionThe data presented in our study indicate that rhein possessed antibacterial activity, which can be potentiated in combination with metronidazole or other polyphenols. In addition, rhein can impair the pathogenicity of P. gingivalis by reducing transcription of genes coding for important virulence factors.

Apoptosis inducing anthraquinone rhein and emodin differentially suppress human dehydroepiandrosterone sulfotransferase (hSULT2A1) and phenol sulfotransferases (hSULT1A1) in Hep-G2 and Caco-2 cells

The anti-cancer and apoptosis-inducing drugs rhein (4, 5-dihydroxyanthraquinone-2-carboxylic acid) and emodin (3methyl-1, 6, 8-trihydro-xyanthrax-quinone) are clinically very important. They modulate cell cycle via tumor suppressor gene, immuno-receptors and ligand activated nuclear receptors. Our recent observation suggests for the first time that 10 days of treatment of either drug with various concentrations (0.01 to 100 M) differentially suppressed the sulfotransferases (SULTs) activities and protein expressions in human hepatocellular carcinoma (Hep G2) and intestinal carcinoma (Caco-2) cell lines. SULTs are phase II drug metabolizing enzymes which catalyze the sulfuryl group transfer to hydroxyl containing endobiotics and xenobiotics. In the present investigation, dehydroepiandrosterone SULT (hSULT1A1) was markedly suppressed by these drugs in human cells. This is the first time report which demonstrates that rhein and emodin may regulate human SULTs. Our finding has important physiological and clinical implications. It will help in the understanding of the SULTs regulations by clinically important drugs and xenobiotics. In future, these drugs may be used in a better defined manner, taking into account its SULTs suppression effects with possible physiological consequences.

Bioactivation and Toxicity of Two Anthraquinones in V79 Chinese Hamster Cells

The role of the flavoprotein NADPH cytochrome P450 reductase, NADH-dehydrogenase and DT-diaphorase in the biotransformation of the anthraquinones rhein and danthron was investigated using purified enzymes, subcellular fractions and cell cultures. The results demonstrated that rhein was more able than danthron to produce O2 by P450 reductase, NADH-dehydrogenase and V79 homogenate and microsomes, and this may explain its higher toxicity to V79 cells. In addition, unlike other quinones, DT-diaphorase appeared not to play a detoxication role in rhein and danthron biotransformation. On the contrary, by inhibiting DT-diaphorase with dicoumarol, the rhein- and danthron-derived cytotoxicity in V79 cells was reduced. This finding suggests that, for these quinones, other coumarol-sensitive biotransformation routes are operative in V79 cells.

Detection of anthraquinone laxatives in the urine

A method is described to detect anthraquinones in the urine after oral intake of vegetable laxatives and danthron. After oxidative hydrolysis the free anthraquinones are extracted in benzene and separated by means of thin layer chromatography. Besides other anthraquinones rhein was always found, even when it was not present in the administered drug. Probably there is an oxidation in the body of aloe-emodin and chrysophanol to rhein.