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Biomedicine & Pharmacotherapy =... Sep 2022In folk medicine, Aloe, a genus of Aloaceae, is constantly developed into laxative drugs or products and skin remedies with tremendous popularity worldwide. However,... (Review)
Review
In folk medicine, Aloe, a genus of Aloaceae, is constantly developed into laxative drugs or products and skin remedies with tremendous popularity worldwide. However, almost all products of Aloe are in roughly processed form. Therefore, developing related products of the active ingredients derived from Aloe is of great medical value. Aloin is a quality standard compound based on the Chinese Pharmacopoeia (CHP). It has a wide range of pharmacological activities, including anti-tumor, anti-inflammatory, anti-osteoporotic, organ-protective, anti-viral, anti-microbial, anti-parasitic, and laxative potentials. Moreover, it regulates blood lipids and glucose and improves neuropathic pain effects, depicting potential to be transformed into promising medicines and healthcare products. In addition to the functional cosmetics and health products of Aloe, the availability, pharmacological activities, pharmacokinetics, formulation studies, and toxicity of aloin were summarized after investigating the literature from PubMed, Google, and other databases. Moreover, significant attention had been paid to the development of aloin-derived medicines and healthcare products. Thus, the present review clarified the possibility of aloin as medicines and healthcare products to develop and utilize Aloe resources.
Topics: Aloe; Anthraquinones; Anti-Inflammatory Agents; Antiviral Agents; Delivery of Health Care; Emodin; Laxatives
PubMed: 36076485
DOI: 10.1016/j.biopha.2022.113421 -
Nucleic Acids Research Jan 2023Thermorubin (THR) is an aromatic anthracenopyranone antibiotic active against both Gram-positive and Gram-negative bacteria. It is known to bind to the 70S ribosome at...
Thermorubin (THR) is an aromatic anthracenopyranone antibiotic active against both Gram-positive and Gram-negative bacteria. It is known to bind to the 70S ribosome at the intersubunit bridge B2a and was thought to inhibit factor-dependent initiation of translation and obstruct the accommodation of tRNAs into the A site. Here, we show that thermorubin causes ribosomes to stall in vivo and in vitro at internal and termination codons, thereby allowing the ribosome to initiate protein synthesis and translate at least a few codons before stalling. Our biochemical data show that THR affects multiple steps of translation elongation with a significant impact on the binding stability of the tRNA in the A site, explaining premature cessation of translation. Our high-resolution crystal and cryo-EM structures of the 70S-THR complex show that THR can co-exist with P- and A-site tRNAs, explaining how ribosomes can elongate in the presence of the drug. Remarkable is the ability of THR to arrest ribosomes at the stop codons. Our data suggest that by causing structural re-arrangements in the decoding center, THR interferes with the accommodation of tRNAs or release factors into the ribosomal A site.
Topics: Anti-Bacterial Agents; Codon, Terminator; Gram-Negative Bacteria; Gram-Positive Bacteria; Ribosomes; Protein Biosynthesis; Anthraquinones
PubMed: 36546783
DOI: 10.1093/nar/gkac1189 -
International Journal of Environmental... Aug 2022Objective: This study was conducted to evaluate the acute and subchronic toxicity of anthraquinone. An acute toxicity test was performed in female Sprague Dawley (SD)...
Objective: This study was conducted to evaluate the acute and subchronic toxicity of anthraquinone. An acute toxicity test was performed in female Sprague Dawley (SD) rats, and the oral median lethal dose (LD50) of anthraquinone was estimated to be >5000 mg/kg body weight (BW). In the subchronic study, groups of 10 male and 10 female rats were dosed with anthraquinone by gavage at 0, 1.36, 5.44, 21.76, and 174.08 mg/kg BW, 7 days/week for 90 days followed by a recovery period of 28 days. No appreciable toxic-related changes were observed in the 1.36 mg/kg BW group. When the animals received 5.44 mg/kg BW or more of anthraquinone, hyaline droplet accumulation in the renal tubules was observed in both the male and female rats, and anemia was observed in the females. When the anthraquinone dose reached 174.08 mg/kg BW, mild hepatocellular hypertrophy around the central vein of the hepatic lobule and hypothyroidism were observed in the female rats. During the recovery period, changes in clinical symptoms and parameters were considerably alleviated. Based on the results of this study, the no observed adverse effect level (NOAEL) for anthraquinone in rats was set at 1.36 mg/kg BW, and the lowest observed adverse effect level (LOAEL) was 5.44 mg/kg BW.
Topics: Administration, Oral; Animals; Anthraquinones; Body Weight; Female; Male; No-Observed-Adverse-Effect Level; Organ Size; Rats; Rats, Sprague-Dawley; Toxicity Tests, Acute; Toxicity Tests, Subchronic
PubMed: 36012048
DOI: 10.3390/ijerph191610413 -
Angewandte Chemie (International Ed. in... Mar 2021Sulfur incorporation into natural products is a critical area of biosynthetic studies. Recently, a subset of sulfur-containing angucyclines has been discovered, and yet,...
Sulfur incorporation into natural products is a critical area of biosynthetic studies. Recently, a subset of sulfur-containing angucyclines has been discovered, and yet, the sulfur incorporation step is poorly understood. In this work, a series of thioether-bridged angucyclines were discovered, and a cryptic epoxide Michael acceptor intermediate was revealed en route to thioangucyclines (TACs) A and B. However, systematic gene deletion of the biosynthetic gene cluster (BGC) by CRISPR/Cas9 could not identify any gene responsible for the conversion of the epoxide intermediate to TACs. Instead, a series of in vitro and in vivo experiments conclusively showed that the conversion is the result of two non-enzymatic steps, possibly mediated by endogenous hydrogen sulfide. Therefore, the TACs are proposed to derive from a detoxification process. These results are expected to contribute to the study of both angucyclines and the utilization of inorganic sulfur in natural product biosynthesis.
Topics: Anthraquinones; Molecular Conformation; Sulfhydryl Compounds; Sulfur
PubMed: 33465268
DOI: 10.1002/anie.202015570 -
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 -
Bioorganic & Medicinal Chemistry Oct 2019In order to overcome therapy resistance in cancer, scientists search in nature for novel lead structures for the development of improved chemotherapeutics.... (Review)
Review
In order to overcome therapy resistance in cancer, scientists search in nature for novel lead structures for the development of improved chemotherapeutics. Anthraquinones belong to a class of tricyclic organic natural compounds with promising anti-cancer effects. Anthraquinone derivatives are rich in structural diversity, and exhibit pleiotropic properties, among which the modulation of autophagy seems promising in the context of overcoming cancer-therapy resistance. Among the most promising derivatives in this regard are emodin, aloe emodin, rhein, physcion, chrysophanol and altersolanol A. On the molecular level, these compounds target autophagy via different upstream pathways including the AKT/mTOR-axis and transcription of autophagy-related proteins. The role of autophagy is pro-survival as well as cell death-promoting, depending on derivatives and their cell type specificity. This review summarizes observed effects of anthraquinone derivatives on autophagy and discusses targeted pathways and crosstalks. A cumulative knowledge about this topic paves the way for further research on modes of action, and aids to find a therapeutic window of anthraquinones in cancer-therapy.
Topics: Animals; Anthraquinones; Antineoplastic Agents; Autophagy; Cell Death; Dose-Response Relationship, Drug; Humans; Molecular Structure; Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Structure-Activity Relationship; TOR Serine-Threonine Kinases
PubMed: 31420258
DOI: 10.1016/j.bmc.2019.115042 -
Fitoterapia Mar 2023Emodin is the main pharmacodynamic components of rhubarb, with significant pharmacological effects and clinical efficacy.Emodin has a variety of therapy effects, such as... (Review)
Review
Emodin is the main pharmacodynamic components of rhubarb, with significant pharmacological effects and clinical efficacy.Emodin has a variety of therapy effects, such as anti-cancer, anti-fibrosis effects, and is widely used to treat encephalitis, diabetic cataract and organ fibrosis. Several studies have shown that emodin has a good treatment effect on organ fibrosis, but the mechanism is complex. Moreover, the evidence of some studies is conflicting and confusing. This paper reviewed the mechanism, pharmacokinetics and toxicology of emodin in fibrosis treatment, and briefly discussed relevant cutting-edge new formulations to improve the efficacy, the result can provide some reference for future study.
Topics: Rats; Animals; Emodin; Anthraquinones; Rats, Sprague-Dawley; Molecular Structure; Plant Extracts; Rheum
PubMed: 36436587
DOI: 10.1016/j.fitote.2022.105358 -
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 -
Journal of the American Chemical Society Nov 2022First discovered in 1989, the anthraquinone-fused enediynes are a class of DNA-cleaving bacterial natural products composed of a DNA-intercalating anthraquinone moiety...
First discovered in 1989, the anthraquinone-fused enediynes are a class of DNA-cleaving bacterial natural products composed of a DNA-intercalating anthraquinone moiety and a 10-membered enediyne warhead. However, until recently, there has been a lack of genetically amenable hosts and sequenced biosynthetic gene clusters available for solving the biosynthetic questions surrounding these molecules. Herein, we have identified and biochemically and structurally characterized TnmK1, a member of the α/β-hydrolase fold superfamily responsible for the C-C bond formation linking the anthraquinone moiety and enediyne core together in tiancimycin (TNM) biosynthesis. In doing so, two intermediates, TNM H and TNM I, in anthraquinone-fused enediyne biosynthesis, containing an unprecedented cryptic C16 aldehyde group, were identified. This aldehyde plays a key role in the TnmK1-catalyzed C-C bond formation via a Michael addition, representing the first example of this chemistry for the α/β-hydrolase fold superfamily. Additionally, TNM I shows sub-nanomolar cytotoxicity against selected cancer cell lines, indicating a new mechanism of action compared to previously known anthraquinone-fused enediynes. Together, the findings from this study are expected to impact enzymology, natural product biosynthesis, and future efforts at enediyne discovery and drug development.
Topics: Enediynes; Anthraquinones; Biological Products; Hydrolases; Aldehydes
PubMed: 36279548
DOI: 10.1021/jacs.2c08957 -
Molecules (Basel, Switzerland) Sep 2022We report the use of electrogenerated anthraquinone radical anion (AQ•) to trigger fast catalytic depolymerization of polymers derived from poly(dithiothreitol)...
We report the use of electrogenerated anthraquinone radical anion (AQ•) to trigger fast catalytic depolymerization of polymers derived from poly(dithiothreitol) (pDTT)-a self-immolative polymer (SIP) with a backbone of dithiothreitols connected with disulfide bonds and end-capped via disulfide bonds to pyridyl groups. The pDTT derivatives studied include polymers with simple thiohexyl end-caps or modified with AQ or methyl groups by Steglich esterification. All polymers were shown to be depolymerized using catalytic amounts of electrons delivered by AQ•. For pDTT, as little as 0.2 electrons per polymer chain was needed to achieve complete depolymerization. We hypothesize that the reaction proceeds with AQ• as an electron carrier (either molecularly or as a pendant group), which transfers an electron to a disulfide bond in the polymer in a dissociative manner, generating a thiyl radical and a thiolate. The rapid and catalytic depolymerization is driven by thiyl radicals attacking other disulfide bonds internally or between pDTT chains in a chain reaction. Electrochemical triggering works as a general method for initiating depolymerization of pDTT derivatives and may likely also be used for depolymerization of other disulfide polymers.
Topics: Anions; Anthraquinones; Disulfides; Dithiothreitol; Polymers
PubMed: 36234828
DOI: 10.3390/molecules27196292