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Food and Chemical Toxicology : An... Nov 2023Over the past decades, androgen receptor (AR) signaling has been a key driver of both primary and recurrent prostate cancer. In this work, aloe-emodin was identified as...
Over the past decades, androgen receptor (AR) signaling has been a key driver of both primary and recurrent prostate cancer. In this work, aloe-emodin was identified as a novel AR antagonist, effectively inhibiting AR signaling. Firstly, aloe-emodin can inhibit LNCaP cell growth by promoting apoptosis. Then, the results of Western blot and quantitative real-time PCR further confirmed that aloe-emodin modulated AR protein levels by promoting AR proteasomal degradation, and also inhibited the transcription of the AR downstream target genes, including PSA, KLK2, and TMPRSS2. Furthermore, the result of immunofluorescence showed that aloe-emodin prevented the nuclear translocation of AR. Molecular docking and molecular dynamics simulation suggested that aloe-emodin combined with AR to form stable complexes, which might explain that aloe-emodin prevented the translocation of AR from the cytoplasm to the nucleus by affecting the ligand binding of AR. Therefore, aloe-emodin as a novel AR antagonist may play a crucial role in promoting cancer prevention or complementing pharmacological therapies in the treatment of prostate cancer.
Topics: Male; Humans; Emodin; Receptors, Androgen; Aloe; Molecular Docking Simulation; Cell Line, Tumor; Anthraquinones; Prostatic Neoplasms; Apoptosis; Androgen Receptor Antagonists
PubMed: 37806336
DOI: 10.1016/j.fct.2023.114092 -
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 -
Biomedicine & Pharmacotherapy =... May 2022Emodin is an anthraquinone derivative found in the roots and bark of a variety of plants, molds, and lichens. Emodin has been used as a traditional medication for more... (Review)
Review
Emodin is an anthraquinone derivative found in the roots and bark of a variety of plants, molds, and lichens. Emodin has been used as a traditional medication for more than 2000 years and is still common in numerous herbal drugs. Emodin is plentiful in the three plant families, including Polygonaceae (Rheum, Rumex, and Polygonum spp.), Fabaceae (Cassia spp.), and Rhamnaceae (Rhamnus, Frangula, and Ventilago spp.). Emerging experimental evidences indicate that emodin confers a wide range of pharmacological activities; special focus was implemented toward neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, cerebral ischemia, anxiety and depression, schizophrenia, chronic hyperglycemic peripheral neuropathy, etc. Numerous preclinical evidences were established in support of the neuroprotection of emodin. However, this review highlighted the role of emodin as a potent neurotherapeutic agent; therefore, its evidence-based functionality on neurological disorders (NDs).
Topics: Anthraquinones; Emodin; Neuroprotective Agents; Rhamnus; Rheum
PubMed: 35367766
DOI: 10.1016/j.biopha.2022.112877 -
Journal of Biomolecular Structure &... Feb 2020A new anthraquinone [1-(2-Aminoethyl)piperazinyl-9,10-dioxo-anthraquinone] derivative was synthesized and characterized by density functional theory (DFT) calculations,...
A new anthraquinone [1-(2-Aminoethyl)piperazinyl-9,10-dioxo-anthraquinone] derivative was synthesized and characterized by density functional theory (DFT) calculations, experimental and theoretical vibrational spectroscopy and NMR techniques. The most stable molecular structure of the title molecule was determined by DFT B3LYP method with 6-31++G(d,p) and 6-311++G(d,p) basis sets. The fundamental vibrational wavenumbers, IR and Raman intensities for the optimized structure of the investigated molecule were calculated and compared with the experimental vibrational spectra. The vibrational assignment of the molecule was done using the potential energy distribution analysis. The molecular electrostatic potential (MEP), highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LUMO) were also calculated. The antibacterial activities of the new anthraquinone derivative against Gram-positive and Gram-negative bacteria were determined, and it was shown that the highest effectiveness was against and while no activity was against Gram-negative bacteria. Moreover, the antimycotic activity of the title compound was examined and the cytotoxicity of anthraquinone derivate was determined. In order to find the possible inhibitory activity of the title compound, molecular docking of the molecule was carried out against DNA. The results indicated that the mentioned compound has a good binding affinity to interact with the DC3, DG4, DA5, DC21 and DC23 residues of DNA via the intermolecular hydrogen bonds. [Formula: see text] Communicated by Ramaswamy H. Sarma.
Topics: A549 Cells; Anthraquinones; Anti-Bacterial Agents; Bacteria; Cell Death; Cell Proliferation; DNA; Fungi; Humans; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Molecular Conformation; Molecular Docking Simulation; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Static Electricity; Vibration
PubMed: 30890106
DOI: 10.1080/07391102.2019.1587513 -
Molecules (Basel, Switzerland) Oct 2022Currently, both acute kidney injury (AKI) and chronic kidney disease (CKD) are considered to be the leading public health problems with gradually increasing incidence... (Review)
Review
Currently, both acute kidney injury (AKI) and chronic kidney disease (CKD) are considered to be the leading public health problems with gradually increasing incidence rates around the world. Rhein is a monomeric component of anthraquinone isolated from rhubarb, a traditional Chinese medicine. It has anti-inflammation, anti-oxidation, anti-apoptosis, anti-bacterial and other pharmacological activities, as well as a renal protective effects. Rhein exerts its nephroprotective effects mainly through decreasing hypoglycemic and hypolipidemic, playing anti-inflammatory, antioxidant and anti-fibrotic effects and regulating drug-transporters. However, the latest studies show that rhein also has potential kidney toxicity in case of large dosages and long use times. The present review highlights rhein's molecular targets and its different effects on the kidney based on the available literature and clarifies that rhein regulates the function of the kidney in a positive and negative way. It will be helpful to conduct further studies on how to make full use of rhein in the kidney and to avoid kidney damage so as to make it an effective kidney protection drug.
Topics: Anthraquinones; Antioxidants; Humans; Hypoglycemic Agents; Kidney; Renal Insufficiency, Chronic
PubMed: 36235108
DOI: 10.3390/molecules27196572 -
International Journal of Biological... 2022Cancers are generally recognized as the leading cause of death and a predominant barrier to prolonging life expectancy in both developed and developing countries. Emodin... (Review)
Review
Cancers are generally recognized as the leading cause of death and a predominant barrier to prolonging life expectancy in both developed and developing countries. Emodin is a typical anthraquinone derivative from various plants that exhibits a wide spectrum of biological activities, such as anticancer, antibacterial, hepatoprotective and anti-inflammatory activities. Much previous preclinical evidence has demonstrated that emodin exhibits reliable effects on several cancer types, including lung cancer, liver cancer, colon cancer, breast cancer, pancreatic cancer, leukemia, cervical cancer, and ovarian cancer, . The related molecular mechanisms corresponding to the anticancer activities of emodin are involved in the induction of apoptosis, inhibition of cell proliferation, enhanced reactive oxygen species (ROS) accumulation, and induction of autophagy, . In the present review, we summarized the sources, anticancer properties and , molecular mechanisms, metabolic transformation and toxicities of emodin. In addition, we also discussed the limitations of the present investigations of emodin against cancers and gave some perspectives for them, which would be beneficial for the further exploration and development of this natural compound as a clinical cancer drug.
Topics: Anthraquinones; Antineoplastic Agents; Apoptosis; Colonic Neoplasms; Emodin; Humans
PubMed: 35637953
DOI: 10.7150/ijbs.70447 -
Toxicology Aug 2022Cassiae semen (CS), a traditional Chinese medicine, has various bioactivities in preclinical and clinical practice. Aurantio-obtusin (AO) is a major anthraquinone (AQ)...
Cassiae semen (CS), a traditional Chinese medicine, has various bioactivities in preclinical and clinical practice. Aurantio-obtusin (AO) is a major anthraquinone (AQ) ingredient derived from CS, and has drawn public concerns over its potential hepatotoxicity. We previously found that AO induces hepatic necroinflammation by activating NOD-like receptor protein 3 inflammasome signaling. However, the mechanisms contributing to AO-motivated hepatotoxicity remain unclear. Herein, we evaluated hepatotoxic effects of AO on three liver cell lines by molecular and biochemical analyses. We found that AO caused cell viability inhibition and biochemistry dysfunction in the liver cells. Furthermore, AO elevated reactive oxygen species (ROS), followed by mitochondrial dysfunction (decreases in mitochondrial membrane potential and adenosine triphosphate) and apoptosis (increased Caspase-3, Cleaved caspase-3, Cytochrome c and Bax expression, and decreased Bcl-2 expression). We also found that AO increased the lipid peroxidation (LPO) and enhanced ferroptosis by activating cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding (CREB) pathway (increases in PKA, p-CREB, acyl-CoA synthetase long chain family member 4). Based on these results, we used an AOP framework to explore the mechanisms underlying AO's hepatotoxicity. It starts from molecular initiating event (ROS), and follows two critical toxicity pathways (i.e., mitochondrial dysfunction-mediated apoptosis and LPO-enhanced ferroptosis) over a series of key events (KEs) to the adverse outcome of hepatotoxicity. The results of an assessment confidence in the adverse outcome pathway (AOP) framework supported the evidence concordance in dose-response, temporal and incidence relationships between KEs in AO-induced hepatotoxicity. This study's findings offer a novel toxicity pathway network for AO-caused hepatotoxicity.
Topics: Adverse Outcome Pathways; Anthraquinones; Caspase 3; Chemical and Drug Induced Liver Injury; Humans; Reactive Oxygen Species
PubMed: 35995123
DOI: 10.1016/j.tox.2022.153293 -
Natural Product Research Oct 2020Two new anthraquinone derivatives, selaginones A () and B (), and one new triarylbenzophenone analog, selagibenzophenone B (), were isolated from (Beauv.) Spring. Their...
Two new anthraquinone derivatives, selaginones A () and B (), and one new triarylbenzophenone analog, selagibenzophenone B (), were isolated from (Beauv.) Spring. Their structures were established by 1D-, 2D-NMR and HR-ESI-MS data. Compounds and represent the uncommon examples of aryl substituted anthraquinone derivatives. Especially, compound is a unique anthranone with exceptional structural feature, in which a -hydroxyphenyl moiety is attached to the C-10 position. Compound is the second naturally occurring triarylbenzophenone and showed moderate activity against SMCC-7721 and MHCC97-H cell lines with IC values of 39.8, 51.5 μM respectively.
Topics: Anthraquinones; Antineoplastic Agents, Phytogenic; Benzophenones; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Inhibitory Concentration 50; Liver Neoplasms; Magnetic Resonance Spectroscopy; Molecular Structure; Plants, Medicinal; Selaginellaceae; Spectrometry, Mass, Electrospray Ionization
PubMed: 29658323
DOI: 10.1080/14786419.2018.1452008 -
Journal of Biomolecular Structure &... Oct 20191, 4 and 5, 8-Positions as well as type of functionalities on these positions at anthraquinone-9, 10-dione are proposed to be significant for anticancer activity....
1, 4 and 5, 8-Positions as well as type of functionalities on these positions at anthraquinone-9, 10-dione are proposed to be significant for anticancer activity. Therefore, keeping this into consideration, a series of 1-substituted anthraquinone-based compounds are designed, synthesized, characterized and biologically evaluated for anticancer activity. The structure of synthesized compounds is confirmed by spectroscopic analysis, i.e. 1D (H and C) nuclear magnetic resonance (NMR), electrospray ionization-mass spectrometry (ESI-MS) studies and Fourier transform infrared (FT-IR) tools. Synthesized 1-substituted anthraquinone compounds showed cytotoxic effect against human breast cancer cell line (MCF-7), human prostate cancer cell line (PC-3) and Hela derivative human cell line (Hep 2C) (Hela derivative) cell lines. All the compounds showed mild antibacterial property in comparison to standard antibiotic streptomycin against Gram + ve and -ve bacteria. They also exhibit mild antifungal activity. calf thymus (ct)-DNA binding studies of synthesized series using UV-visible absorption spectra measurement and fluorescence tools indicate partial intercalative mode of binding. Electronic properties of synthesized analogues and mitoxantrone are compared using highest occupied molecular orbital-lowest occupied molecular orbital (HOMO-LUMO) calculation. Low energy gap between HOMO and LUMO of 1-substituted anthraquinone compounds indicates the highly charged structure of the molecules in comparison to mitoxantrone, and the same is proposed to be responsible for comparable cytotoxic activities of the synthesized 1-substituted anthraquinone molecules. Docking interaction of synthesized 1-substituted anthraquinone compounds and i-motif sequence indicates intercalative mode of binding of compounds with telomeric junction. Communicated by Ramaswamy H. Sarma.
Topics: Anthraquinones; Antifungal Agents; Antioxidants; Cell Cycle; Cell Death; Cell Line, Tumor; DNA; Humans; Inhibitory Concentration 50; Kinetics; Methotrexate; Microbial Sensitivity Tests; Molecular Docking Simulation; Nucleic Acid Conformation; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Sulfonamides; Thermodynamics
PubMed: 30489230
DOI: 10.1080/07391102.2018.1552198 -
Journal of Applied Toxicology : JAT Sep 2021Anthraquinones exhibit various pharmacological activities (e.g., antioxidant and laxative) and are commonly found in consumer products including foods, dietary...
Anthraquinones exhibit various pharmacological activities (e.g., antioxidant and laxative) and are commonly found in consumer products including foods, dietary supplements, drugs, and traditional medicines. Despite their widespread use, there are limited data available on their toxicokinetic properties. Cytochrome P450 enzymes (CYPs) in the liver play major roles in metabolizing exogenous chemicals (e.g., pharmaceuticals, food ingredients, and environmental pollutants) and endogenous biomolecules (e.g., steroid hormones and cholesterol). Inhibition of CYP activities may lead to serious interactions among these compounds. Here, in silico (quantitative structure-activity relationship modeling) and in vitro (human recombinant enzymes and liver microsomes) methods were used to identify inhibitors of five major CYP isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) among 22 anthraquinones. First, in silico prediction and in vitro human recombinant enzyme assays were conducted for all compounds, and results showed that most of the anthraquinones were potent CYP1A2 inhibitors. Second, five selected anthraquinones (emodin, aloe-emodin, rhein, purpurin, and rubiadin) were further evaluated in human liver microsomes. Finally, plasma concentrations of the five anthraquinones in animal and humans were identified in the literature and compared to their in vitro inhibition potency (IC values) towards CYP activities. Emodin, rhein, and aloe-emodin inhibited activities of multiple CYPs in human liver microsomes and potential in vivo inhibition may occur due to their high plasma concentrations. These in silico and in vitro results enabled rapid identification of potential CYP inhibitors and prioritized future in-depth studies.
Topics: Animals; Anthraquinones; Computer Simulation; Cytochrome P-450 CYP1A2; Cytochrome P-450 Enzyme Inhibitors; Emodin; Humans; In Vitro Techniques; Isoenzymes; Microsomes, Liver; Quantitative Structure-Activity Relationship; Recombinant Proteins
PubMed: 33438235
DOI: 10.1002/jat.4134