-
Journal of Controlled Release :... Feb 2022Breast cancer is the most common cancer among women and a leading cause of death worldwide. Triple negative breast cancer (TNBC) is a highly aggressive subtype which is...
Breast cancer is the most common cancer among women and a leading cause of death worldwide. Triple negative breast cancer (TNBC) is a highly aggressive subtype which is the most challenging to treat. Due to heterogeneity and a lack of specific molecular targets, small molecule-based chemotherapy is the preferred course of treatment. However, these drugs have high toxicity due to off-target effects on healthy tissues, and tumors may develop resistance. Here, we present a polyethylene glycol-modified nanoscale liposomal formulation (LipoRV) of a new anthraquinone derivative which has potent effects on multiple TNBC cell lines. LipoRV readily inhibited the cell cycle, induced cell apoptosis, and reduced long-term proliferative potential of TNBC cells. In a xenograft animal model, LipoRV successfully cleared tumors and demonstrated a good safety profile, without detrimental effects on biochemical markers. Finally, RNA sequencing of LipoRV-treated TNBC cells was carried out, indicating that LipoRV may have immunomodulatory properties. These findings demonstrate that a liposomal anthraquinone-based molecule has excellent promise for TNBC therapy in the future.
Topics: Animals; Anthraquinones; Apoptosis; Cell Line, Tumor; Cell Proliferation; Female; Humans; Liposomes; Triple Negative Breast Neoplasms; Xenograft Model Antitumor Assays
PubMed: 34896187
DOI: 10.1016/j.jconrel.2021.12.001 -
International Journal of Molecular... Oct 2023Breast cancer (BC) is the most common malignancy among women worldwide. In recent years, significant progress has been made in BC therapy. However, serious side effects... (Review)
Review
Breast cancer (BC) is the most common malignancy among women worldwide. In recent years, significant progress has been made in BC therapy. However, serious side effects resulting from the use of standard chemotherapeutic drugs, as well as the phenomenon of multidrug resistance (MDR), limit the effectiveness of approved therapies. Advanced research in the BC area is necessary to create more effective and safer forms of therapy to improve the outlook for individuals diagnosed with this aggressive neoplasm. For decades, plants and natural products with anticancer properties have been successfully utilized in treating various medical conditions. Anthraquinone derivatives are tricyclic secondary metabolites of natural origin that have been identified in plants, lichens, and fungi. They represent a few botanical families, e.g., Rhamnaceae, Rubiaceae, Fabaceae, Polygonaceae, and others. The review comprehensively covers and analyzes the most recent advances in the anticancer activity of 1,8-dihydroanthraquinone derivatives (emodin, aloe-emodin, hypericin, chrysophanol, rhein, and physcion) applied both individually, or in combination with other chemotherapeutic agents, in in vitro and in vivo BC models. The application of nanoparticles for in vitro and in vivo evidence in the context of 1,8-dihydroanthraquinone derivatives was also described.
Topics: Humans; Female; Emodin; Breast Neoplasms; Rheum; Anthraquinones; Plant Extracts; Polygonaceae
PubMed: 37958772
DOI: 10.3390/ijms242115789 -
Drug Design, Development and Therapy 2021Anthraquinones (AQs) are found in a variety of consumer products, including foods, nutritional supplements, drugs, and traditional medicines, and have a wide range of... (Review)
Review
Anthraquinones (AQs) are found in a variety of consumer products, including foods, nutritional supplements, drugs, and traditional medicines, and have a wide range of pharmacological actions. Rubiadin, a 1,3-dihydroxy-2-methyl anthraquinone, primarily originates from Linn (Rubiaceae). It was first discovered in 1981 and has been reported for many biological activities. However, no review has been reported so far to create awareness about this molecule and its role in future drug discovery. Therefore, the present review aimed to provide comprehensive evidence of Rubiadin's phytochemistry, biosynthesis, physicochemical properties, biological properties and therapeutic potential. Relevant literature was gathered from numerous scientific databases including PubMed, ScienceDirect, Scopus and Google Scholar between 1981 and up-to-date. The distribution of Rubiadin in numerous medicinal plants, as well as its method of isolation, synthesis, characterisation, physiochemical properties and possible biosynthesis pathways, was extensively covered in this review. Following a rigorous screening and tabulating, a thorough description of Rubiadin's biological properties was gathered, which were based on scientific evidences. Rubiadin fits all five of Lipinski's rule for drug-likeness properties. Then, the in depth physiochemical characteristics of Rubiadin were investigated. The simple technique for Rubiadin's isolation from and the procedure of synthesis was described. Rubiadin is also biosynthesized via the polyketide and chorismate/o-succinylbenzoic acid pathways. Rubiadin is a powerful molecule with anticancer, antiosteoporotic, hepatoprotective, neuroprotective, anti-inflammatory, antidiabetic, antioxidant, antibacterial, antimalarial, antifungal, and antiviral properties. The mechanism of action for the majority of the pharmacological actions reported, however, is unknown. In addition to this review, an in silico molecular docking study was performed against proteins with PDB IDs: 3AOX, 6OLX, 6OSP, and 6SDC to support the anticancer properties of Rubiadin. The toxicity profile, pharmacokinetics and possible structural modifications were also described. Rubiadin was also proven to have the highest binding affinity to the targeted proteins in an in silico study; thus, we believe it may be a potential anticancer molecule. In order to present Rubiadin as a novel candidate for future therapeutic development, advanced studies on preclinical, clinical trials, bioavailability, permeability and administration of safe doses are necessary.
Topics: Animals; Anthraquinones; Antineoplastic Agents, Phytogenic; Drug Development; Drug Discovery; Humans; Medicine, Traditional; Molecular Docking Simulation; Rubia
PubMed: 34764636
DOI: 10.2147/DDDT.S338548 -
Molecules (Basel, Switzerland) Feb 2022belongs to the genus and is classified as an invasive parasitic plant in agriculture. Despite other species being widely used in herbal medicine due to their... (Review)
Review
belongs to the genus and is classified as an invasive parasitic plant in agriculture. Despite other species being widely used in herbal medicine due to their antimicrobial, antioxidant, antitumor, and anti-inflammatory effects, there are almost no information about the potential of confertus for the treatment of various diseases. In this review we analyzed scientific articles revealing properties of plant's substances against cancer, diabetes, pathogenic bacterial invasions, viruses, inflammation, and oxidative stress for the past 20 years. Compounds dominating in each composition of solvents for extraction were discussed, and common thin layer chromatography(TLC) and high performance liquid chromatography(HPLC) methods for efficient separation of the plant's extract are included. Physico-chemical properties such as solubility, hydrophobicity (Log P), pKa of flavonoids, anthraquinones, and other derivatives are very important for modeling of pharmacokinetic and pharmacodynamics. An overview of clinical studies for abounded selected substances of species is presented.
Topics: Anthraquinones; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Flavonoids; Rumex
PubMed: 35208994
DOI: 10.3390/molecules27041204 -
Molecules (Basel, Switzerland) Aug 2019Herein, a direct strategy to synthesize 3-(2-hydroxybenzoyl)-1-aza-anthraquinones with excellent efficiency, mild conditions, and benign functional group compatibility...
Herein, a direct strategy to synthesize 3-(2-hydroxybenzoyl)-1-aza-anthraquinones with excellent efficiency, mild conditions, and benign functional group compatibility was reported. A variety of 3-formylchromone compounds were employed as compatible substrates and this protocol gave the 3-(2-hydroxybenzoyl)-1-aza-anthraquinone derivatives in good to excellent yields without inert gas and expensive transition metal catalysts. Some compounds displayed good anti-proliferative activities.
Topics: Anthraquinones; Antineoplastic Agents; Cell Proliferation; Chemistry Techniques, Synthetic; Drug Screening Assays, Antitumor; HT29 Cells; HeLa Cells; Humans; Metals; Molecular Structure
PubMed: 31434258
DOI: 10.3390/molecules24163017 -
Mediators of Inflammation 2016Anthraquinone compounds are one of the abundant polyphenols found in fruits, vegetables, and herbs. However, the in vivo anti-inflammatory activity and molecular...
Anthraquinone compounds are one of the abundant polyphenols found in fruits, vegetables, and herbs. However, the in vivo anti-inflammatory activity and molecular mechanisms of anthraquinones have not been fully elucidated. We investigated the activity of anthraquinones using acute inflammatory and nociceptive experimental conditions. Anthraquinone-2-carboxylic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA), one of the major anthraquinones identified from Brazilian taheebo, ameliorated various inflammatory and algesic symptoms in EtOH/HCl- and acetylsalicylic acid- (ASA-) induced gastritis, arachidonic acid-induced edema, and acetic acid-induced abdominal writhing without displaying toxic profiles in body and organ weight, gastric irritation, or serum parameters. In addition, AQCA suppressed the expression of inflammatory genes such as cyclooxygenase- (COX-) 2 in stomach tissues and lipopolysaccharide- (LPS-) treated RAW264.7 cells. According to reporter gene assay and immunoblotting analyses, AQCA inhibited activation of the nuclear factor- (NF-) κB and activator protein- (AP-) 1 pathways by suppression of upstream signaling involving interleukin-1 receptor-associated kinase 4 (IRAK1), p38, Src, and spleen tyrosine kinase (Syk). Our data strongly suggest that anthraquinones such as AQCA act as potent anti-inflammatory and antinociceptive components in vivo, thus contributing to the immune regulatory role of fruits and herbs.
Topics: Acetic Acid; Analgesics; Animals; Anthraquinones; Anti-Inflammatory Agents; Arachidonic Acid; Cyclooxygenase 2; Edema; Lipopolysaccharides; Male; Mice; Mice, Inbred ICR; NF-kappa B; Plant Extracts; RAW 264.7 Cells; Ranitidine; Signal Transduction
PubMed: 27057092
DOI: 10.1155/2016/1903849 -
Structure (London, England : 1993) May 2023In this issue of Structure, Huber et al. identify five O-methyltransferases, and three of them catalyze the sequential methylation of the Gram-negative...
In this issue of Structure, Huber et al. identify five O-methyltransferases, and three of them catalyze the sequential methylation of the Gram-negative bacterium-derived aromatic polyketide anthraquinone AQ-256. They present co-crystal structures with bound AQ-256 and its methylated derivatives, which explains the specificities of these O-methyltransferases.
Topics: Methyltransferases; Methylation; Anthraquinones
PubMed: 37146572
DOI: 10.1016/j.str.2023.04.006 -
Molecules (Basel, Switzerland) Mar 2023The composition of an ethanol extract from the roots of Losinsk of the Trans-Ili Alatau wild flora was studied in order to determine its antiulcer activity. The...
The composition of an ethanol extract from the roots of Losinsk of the Trans-Ili Alatau wild flora was studied in order to determine its antiulcer activity. The phytochemical composition of the anthraquinone-flavonoid complex from (AFC) revealed the presence of numerous polyphenolic compounds, the most abundant of which are anthraquinones (1.77%), flavonoids (6.95%), and tannins (13.39%). The use of column chromatography (CC) and thin-layer chromatography (TLC) in conjunction with UV, IR, NMR spectroscopy, and mass spectrometry data allowed the researchers to isolate and identify the major components of the anthraquinone-flavonoid complex's polyphenol fraction: physcion, chrysophanol, emodin, isorhamnetin, quercetin, and myricetin. The gastroprotective effect of the polyphenolic fraction of the anthraquinone-flavonoid complex (AFC) of roots was examined in an experimental model of rat gastric ulcer induced by indomethacin. The preventive and therapeutic effect of the anthraquinone-flavonoid complex at a dose of 100 mg/kg was analyzed using intragastric administration per day for 1 to 10 days, followed by a histological examination of stomach tissues. It has been demonstrated that prophylactic and prolonged use of the AFC in laboratory animals resulted in significantly less pronounced hemodynamic and desquamative changes in the epithelium of gastric tissues. The acquired results thus offer fresh insight into the anthraquinone and flavonoid metabolite component composition of roots, and they imply that the examined extract can be used to develop herbal medicines with antiulcer activity.
Topics: Rats; Animals; Rumex; Anthraquinones; Plant Extracts; Flavonoids; Anti-Ulcer Agents; Stomach Ulcer
PubMed: 36903594
DOI: 10.3390/molecules28052347 -
BMC Microbiology Dec 2022The demand for natural coloring and preservative agents in food industry is increasing day by day as a result of awareness of the negative health effects of synthetic...
Irradiation impact on biological activities of Anthraquinone pigment produced from Talaromyces purpureogenus and its evaluation, characterization and application in beef burger as natural preservative.
BACKGROUND
The demand for natural coloring and preservative agents in food industry is increasing day by day as a result of awareness of the negative health effects of synthetic color preservatives. Consumers want foods with less processing, a longer shelf life, and clear labels that list only natural ingredients and food additives with familiar names that promote good health. In order to meet consumer demands and regain consumers' confidence in the safety of food products, the food industry was compelled to search for natural alternatives with strong antibacterial and antioxidant properties. Therefore, the objective of this study was to produce a microbial pigment that not only serve as food coloring agents but also provide health advantages owing to their bioactivities. Additionally, the potential use of anthraquinone pigment (AQP) as a natural food preservative compared to gamma irradiation was also examined to extend the shelf life of the beef burger and improve its hygienic quality.
RESULTS
This study used Talaromyces purpureogenus AUMC2603 to produce the red natural pigment, which was identified as an anthraquinone pigment (AQP). According to the results, gamma (γ) radiation had no significant effect on AQP's antibacterial properties. However, it has a negative, considerable effect on antioxidant activity, where a large dose of γ-ray may change the antioxidant components and lessen the AQP's capacity to scavenge free radicals. Additionally, the γ ray-treated AQP had a strong cytotoxic activity in relation to a high γ-ray dose. As a result, it is suggested that AQP-containing foods should not be irradiated. The extracted AQP was applied as a food additive to improve the quality and increase the shelf life of beef burgers. Significant antibacterial and antioxidant action has been shown at 2% (w/v) AQP. The findings demonstrated that the treatment of beef burger with AQP decreased the initial total bacterial count and psychrophilic bacteria and extended the shelf-life of beef burger in comparison to the control (beef burger with no addition of AQP, butylated hydroxytoluene (BHT) or gamma radiation treatment). On the other hand, there was no substantial difference in the overall amount of mold and yeast or coliform at zero time. According to sensory characteristics, beef burgers had a shelf life of 6 days for controls and 9, 12, and 15 days for AQP-treated samples at 0.5, 1 and 2%, respectively, compared to γ- irradiated samples, 9 and 21 days, at 3 and 5 Kilo Gray (KGy), respectively.
CONCLUSIONS
This research provides a natural red pigment from Talaromyces purpureogenus with potent biological activities as antimicrobials and antioxidants to be applied as coloring, additive, and preservative agent in the food industry. Also, the tested pigment offers a powerful alternative to gamma irradiation for extending the shelf life of food products.
Topics: Animals; Cattle; Antioxidants; Colony Count, Microbial; Anti-Bacterial Agents; Anthraquinones
PubMed: 36581795
DOI: 10.1186/s12866-022-02734-4 -
Cells Jan 2022Anthraquinone derivatives exhibit various biological activities, e.g., antifungal, antibacterial and in vitro antiviral activities. They are naturally produced in many...
Anthraquinone derivatives exhibit various biological activities, e.g., antifungal, antibacterial and in vitro antiviral activities. They are naturally produced in many fungal and plant families such as Rhamnaceae or Fabaceae. Furthermore, they were found to have anticancer activity, exemplified by mitoxantrone and pixantrone, and many are well known redox-active compounds. In this study, various nature inspired synthetic anthraquinone derivatives were tested against colon, prostate, liver and cervical cancer cell lines. Most of the compounds exhibit anticancer effects against all cell lines, therefore the compounds were further studied to determine their IC-values. Of these compounds, 1,4-bis(benzyloxy)-2,3-bis(hydroxymethyl)anthracene-9,10-dione () exhibited the highest cytotoxicity against PC3 cells and was chosen for a deeper look into its mechanism of action. Based on flow cytometry, the compound was proven to induce apoptosis through the activation of caspases and to demolish the ROS/RNS and NO equilibrium in the PC3 cell line. It trapped cells in the G2/M phase. Western blotting was performed for several proteins related to the effects observed. Compound enhanced the production of PARP and caspase-3. Moreover, it activated the conversion of LC3A/B-I to LC3A/B-II showing that also autophagy plays a role in its mechanism of action, and it caused the phosphorylation of p70 s6 kinase.
Topics: Adenine; Anthraquinones; Apoptosis; Autophagy; Caspases; Cell Line, Tumor; Cell Survival; DNA Topoisomerases; Drug Screening Assays, Antitumor; Emodin; Enzyme Activation; G2 Phase; Humans; Inhibitory Concentration 50; Mitosis
PubMed: 35011730
DOI: 10.3390/cells11010168