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BACKGROUND: The search for new bioactive natural compounds with anticancer activity is still of great importance. Even though their potential for diagnostics and treatment of cancer has already been proved, the availability is still limited. Hypericin, a naphthodianthrone isolated essentially from plant source Hypericum perforatum L. along with other related anthraquinones and bisanthraquinones belongs to this group of compounds. Although it has been proven that hypericin is synthesized by the polyketide pathway in plants, none of the candidate genes coding for key enzymes has been experimentally validated yet. Despite the rare occurrence of anthraquinones in plants, their presence in microorganisms, including endophytic fungi, is quite common. Unlike plants, several biosynthetic genes grouped into clusters (BGCs) in fungal endophytes have already been characterized. RESULTS: The aim of this work was to predict, identify and characterize the anthraquinone BGCs in de novo assembled and functionally annotated genomes of selected endophytic fungal isolates (Fusarium oxysporum, Plectosphaerella cucumerina, Scedosporium apiospermum, Diaporthe eres, Canariomyces subthermophilus) obtained from different tissues of Hypericum spp. The number of predicted type I polyketide synthase (PKS) BGCs in the studied genomes varied. The non-reducing type I PKS lacking thioesterase domain and adjacent discrete gene encoding protein with product release function were identified only in the genomes of C. subthermophilus and D. eres. A candidate bisanthraquinone BGC was predicted in C. subthermophilus genome and comprised genes coding the enzymes that catalyze formation of the basic anthraquinone skeleton (PKS, metallo-beta-lactamase, decarboxylase, anthrone oxygenase), putative dimerization enzyme (cytochrome P450 monooxygenase), other tailoring enzymes (oxidoreductase, dehydrogenase/reductase), and non-catalytic proteins (fungal transcription factor, transporter protein). CONCLUSIONS: The results provide an insight into genetic background of anthraquinone biosynthesis in Hypericum-borne endophytes. The predicted bisanthraquinone gene cluster represents a basis for functional validation of the candidate biosynthetic genes in a simple eukaryotic system as a prospective biotechnological alternative for production of hypericin and related bioactive anthraquinones.
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Antraquinonas , Endófitos , Hypericum , Família Multigênica , Policetídeos , Hypericum/microbiologia , Hypericum/genética , Hypericum/metabolismo , Policetídeos/metabolismo , Endófitos/genética , Endófitos/metabolismo , Antraquinonas/metabolismo , Fungos/genética , Genoma Fúngico , Simulação por Computador , Policetídeo Sintases/genética , Perileno/análogos & derivados , Perileno/metabolismo , Antracenos/metabolismo , Genômica , FilogeniaRESUMO
Anthraquinones have attracted considerable interest in the realm of cancer treatment owing to their potent anticancer properties. This study evaluates the potential of a series of new anthraquinone derivatives as anticancer agents for non-small-cell lung cancer (NSCLC). The compounds were subjected to a range of tests to assess their cytotoxic and apoptotic properties, ability to inhibit colony formation, pro-DNA damage functions, and capacity to inhibit the activity of tyrosine kinase proteins (PTKs). Based on the research findings, it has been discovered that most active derivatives (i84, i87, and i90) possess a substantial capability to impede the viability of NSCLC while having mostly a negligible effect on the human kidney cell line. Moreover, the anthraquinones displayed pro-apoptotic and genotoxic attributes while blocking the phosphorylation of multiple PTKs. Collectively, our findings indicate that these derivatives may demonstrate promising potential as effective anticancer agents for lung cancer treatment.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Proteínas Tirosina Quinases , Apoptose , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico , Proliferação de CélulasRESUMO
The purpose of the present work was to develop a phytocosmetic sunscreen emulsion with antioxidant activity and an anti-melanogenic effect, containing an anthraquinone-enriched extract of Rhamnus alaternus (A.E.). Our findings demonstrated that A.E. decreased the levels of reactive oxygen species, DNA damage, and malondialdehyde induced by UVA in human keratinocytes and melanocytes. Furthermore, the calculated SPF value inâ vitro of the cream containing A.E. was 14.26±0.152. Later, it was shown that A.E. extract had an inhibitory effect on the amount of melanin. This extract could also reduce B16F10 intracellular tyrosinase activity. Besides, docking studies were carried out to provide a logical justification for the anti-tyrosinase potential. The findings showed that, A.E. may provide protection against UVA-induced oxidative stress and could be thought of as a viable treatment for hyperpigmentation disorders.
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Rhamnus , Humanos , Antioxidantes/farmacologia , Estresse Oxidativo , Espécies Reativas de Oxigênio , Melaninas , Antraquinonas/farmacologiaRESUMO
INTRODUCTION: Sicklepod [Cassia obtusifolia L. syn Senna obtusifolia (L.) H.S. Irwin & Barneby, Fabaceae] sprouts are promising ingredients with health-promoting benefits. Notwithstanding, the pharmacologically active compounds in sicklepod sprouts have not been studied or analysed in detail. OBJECTIVE: This study aimed to isolate and structurally identify phytochemicals showing α-glucosidase inhibitory activity in sicklepod sprouts and simultaneously quantify the compounds in the sprouts to determine the optimal cultivation method and germination time to maximise active compounds. METHOD: A simultaneous high-performance liquid chromatography-ultraviolet (HPLC-UV) method with high sensitivity and accuracy was developed and used to analyse time-dependent changes in anthraquinone content during sicklepod germination. RESULTS: Thirteen anthraquinones were isolated and identified, of which six-chrysoobtusin, emodin, 1-O-methyl-2-methoxychrysophanol, 7-O-methylobtusin, chrysophanol, and physcion-showed moderate α-glucosidase inhibitory activity. The maximum content of anthraquinones in a sprout was observed on Day 5 under both light and dark conditions. CONCLUSION: The findings of this study revealed that sicklepod sprouts which are promising functional food materials contain a variety of anthraquinones.
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Antraquinonas , Inibidores de Glicosídeo Hidrolases , alfa-Glucosidases , Antraquinonas/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , alfa-Glucosidases/metabolismo , Cassia/química , Senna/química , Germinação/efeitos dos fármacosRESUMO
Content of bioactive constituents is one of the most important characteristics in Rheum palmatum complex. Increasing ingredient content through genetic breeding is an effective strategy to solve the contradiction between large market demand and resource depletion, but currently hampered by limited understanding of metabolite biosynthesis in rhubarb. In this study, deep transcriptome sequencing was performed to compare roots, stems, and leaves of two Rheum species (PL and ZK) that show different levels of anthraquinone contents. Approximately 0.52 billion clean reads were assembled into 58,782 unigenes, of which around 80% (46,550) were found to be functionally annotated in public databases. Expression patterns of differential unigenes between PL and ZK were thoroughly investigated in different tissues. This led to the identification of various differentially expressed genes (DEGs) involved in shikimate, MEP, MVA, and polyketide pathways, as well as those involved in catechin and gallic acid biosynthesis. Some structural enzyme genes were shown to be significantly up-regulated in roots of ZK with high anthraquinone content, implying potential central roles in anthraquinone synthesis. Taken together, our study provides insights for future functional studies to unravel the mechanisms underlying metabolite biosynthesis in rhubarb. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01492-z.
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In this study, J774A.1 macrophages stimulated by lipopolysaccharide(LPS) and adenosine triphosphate(ATP) were used to establish an in vitro model of pyroptosis, and the intervention mechanism of free total rhubarb anthraquinones(FTRAs) on pyroptosis was investigated. J774A.1 macrophages were cultured in vitro, and the experiment was assigned to the control group and groups with different concentrations of LPS(0.25, 0.5, and 1 µg·mL~(-1)) and ATP(1.25, 2.5, and 5 mmol·L~(-1)). An in vitro model of macrophage pyroptosis was established by detecting cell viability through CCK-8, propidium iodide(PI) apoptotic cell staining, lactate dehydrogenase(LDH), interleukin(IL)-18, and tumor necrosis factor(TNF)-α release. Then, J774A.1 macrophages were randomly divided into six groups: blank control group, LPS+ATP group, high-dose FTRA group, and low, medium, and high-dose FTRA pre-protection group. The phenotypic characteristics and key indicators of pyroptosis were detected as the basis for evaluating the effect of FTRAs on pyroptosis induced by LPS and ATP. Western blot and RT-PCR were used to detect the expression levels of protein and mRNA related to the pyroptosis pathway in caspase-1/11 and elucidate the molecular mechanism of the anti-pyroptosis effect. The results showed that the stimulation condition of 0.50 µg·mL~(-1) LPS+5.00 mmol·L~(-1) ATP was the most effective in the in vitro model of macrophage pyroptosis. FTRAs pre-protected cells for 24 h and then can increase cell viability under pyroptosis conditions, alleviate cell damage, lower the positive rate of PI staining, and reduce the release of LDH, IL-18, and TNF-α. FTRAs were able to significantly inhibit the activation of GSDMD proteins and significantly down-regulate the protein expression of the pyroptosis pathway signature molecules, TLR4, NLRP3, cleaved-caspase-1, and cleaved-caspase-11, but they had no significant effect on ASC proteins. FTRAs were also able to significantly inhibit the mRNA expression of caspase-1, caspase-11, and GSDMD. These results indicate that FTRAs have an inhibitory effect on the pyroptosis model induced by LPS and ATP and play an anti-pyroptosis effect by regulating classical and non-classical pyroptosis signaling pathways and reducing the production of inflammatory cytokines.
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Antraquinonas , Macrófagos , Piroptose , Rheum , Piroptose/efeitos dos fármacos , Rheum/química , Animais , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/citologia , Antraquinonas/farmacologia , Antraquinonas/química , Linhagem Celular , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Trifosfato de Adenosina/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Lipopolissacarídeos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Interleucina-18/genética , Interleucina-18/metabolismoRESUMO
Anthraquinones are polycyclic compounds with an unsaturated diketone structure (quinoid moiety). As important secondary metabolites of plants, anthraquinones play an important role in the response of many biological processes and environmental factors. Anthraquinones are common in the human diet and have a variety of biological activities including anticancer, antibacterial, and antioxidant activities that reduce disease risk. The biological activity of anthraquinones depends on the substitution pattern of their hydroxyl groups on the anthraquinone ring structure. However, there is still a lack of systematic summary on the distribution, classification, and biosynthesis of plant anthraquinones. Therefore, this paper systematically reviews the research progress of the distribution, classification, biosynthesis, and regulation of plant anthraquinones. Additionally, we discuss future opportunities in anthraquinone research, including biotechnology, therapeutic products, and dietary anthraquinones.
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INTRODUCTION: Compared to synthetic herbicides, natural products with allelochemical properties can inhibit weed germination, aiding agricultural output with less phytotoxic residue in water and soil. OBJECTIVES: To identify natural product extracts of three Cassia species; C. javanica, C. roxburghii, and C. fistula and to investigate the possible phytotoxic and allelopathic potential. METHODS: Allelopathic activity of three Cassia species extracts was evaluated. To further investigate the active constituents, untergated metabolomics using UPLC-qTOF-MS/MS and ion-identity molecular networking (IIMN) approach was performed to identify and determine the distribution of metabolites in different Cassia species and plant parts. RESULTS: We observed in our study that the plant extracts showed consistent allelopathic activity against seed germination (P < 0.05) and the inhibition of shoot and root development of Chenopodium murale in a dose-dependent manner. Our comprehensive study identified at least 127 compounds comprising flavonoids, coumarins, anthraquinones, phenolic acids, lipids, and fatty acid derivatives. We also report the inhibition of seed germination, shoot growth, and root growth when treated with enriched leaf and flower extracts of C. fistula, and C. javanica, and the leaf extract of C. roxburghii. CONCLUSION: The present study recommends further evaluation of Cassia extracts as a potential source of allelopathic compounds in agricultural systems.
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Cassia , Espectrometria de Massas em Tandem , Metabolômica , Germinação , Extratos Vegetais/farmacologia , Extratos Vegetais/químicaRESUMO
Natural products (NPs) are highly profitable pharmacological tools due to their chemical diversity and ability to modulate biological systems. Accessing new chemical entities while retaining the biological relevance of natural chemotypes is a fundamental goal in the design of novel bioactive compounds. Notably, NPs have played a crucial role in understanding Hedgehog (HH) signalling and its pharmacological modulation in anticancer therapy. However, HH antagonists developed so far have shown several limitations, thus growing interest in the design of second-generation HH inhibitors. Through smart manipulation of the NPs core-scaffold, unprecedented and intriguing architectures have been achieved following different design strategies. This study reports the rational design and synthesis of a first and second generation of anthraquinone-based hybrids by combining the rhein scaffold with variously substituted piperazine nuclei that are structurally similar to the active portion of known SMO antagonists, the main transducer of the HH pathway. A thorough functional and biological investigation identified RH2_2 and RH2_6 rhein-based hybrids as valuable candidates for HH inhibition through SMO antagonism, with the consequent suppression of HH-dependent tumour growth. These findings also corroborated the successful application of the NPs-based hybrid design strategy in the development of novel NP-based SMO antagonists.
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Antineoplásicos , Neoplasias , Humanos , Receptor Smoothened/uso terapêutico , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antraquinonas/farmacologia , Receptores Acoplados a Proteínas G/metabolismoRESUMO
Since ancient times, Morinda species, particularly Morinda citrifolia, have been used for their therapeutic benefits. Iridoids, anthraquinones, coumarins, flavonoids, lignans, phytosterols, and carotenoids are examples of natural substances with bioactivity. Anthraquinone derivatives are the most significant of these chemicals since they are utilized as natural coloring agents and have a wide range of medicinal functions. Utilizing cell and organ cultures of Morinda species, various biotechnological methods have been developed for the bioproduction of anthraquinone derivatives. The generation of anthraquinone derivatives in cell and organ cultures is summarized in this article. The methods used to produce these chemicals in bioreactor cultures have also been examined. KEY POINTS: ⢠This review investigates the potential of cell and organ cultures for anthraquinone synthesis. ⢠The overproduction of anthraquinones has been addressed using a variety of techniques. ⢠The use of bioreactor technologies for anthraquinone manufacturing is highlighted.
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Lignanas , Morinda , Técnicas de Cultura de Órgãos , Morinda/química , Antraquinonas/química , Extratos Vegetais/químicaRESUMO
New anthraquinone derivatives acruciquinones A-C (1-3), together with ten known metabolites, were isolated from the obligate marine fungus Asteromyces cruciatus KMM 4696. Acruciquinone C is the first member of anthraquinone derivatives with a 6/6/5 backbone. The structures of isolated compounds were established based on NMR and MS data. The absolute stereoconfigurations of new acruciquinones A-C were determined using ECD and quantum chemical calculations (TDDFT approach). A plausible biosynthetic pathway of the novel acruciquinone C was proposed. Compounds 1-4 and 6-13 showed a significant antimicrobial effects against Staphylococcus aureus growth, and acruciquinone A (1), dendryol B (4), coniothyrinone B (7), and ω-hydroxypachybasin (9) reduced the activity of a key staphylococcal enzyme, sortase A. Moreover, the compounds, excluding 4, inhibited urease activity. We studied the effects of anthraquinones 1, 4, 7, and 9 and coniothyrinone D (6) in an in vitro model of skin infection when HaCaT keratinocytes were cocultivated with S. aureus. Anthraquinones significantly reduce the negative impact of S. aureus on the viability, migration, and proliferation of infected HaCaT keratinocytes, and acruciquinone A (1) revealed the most pronounced effect.
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Ascomicetos , Infecções Estafilocócicas , Staphylococcus aureus , Antraquinonas/farmacologiaRESUMO
In this study, seven novel anthraquinones (1-7) and four described anthraquinones (8-11) were purified from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220. It is worth noting that only analogs of 4 and 5 have been reported as natural products to date, while the nuclei of compounds 1-3, 6 and 7 were isolated for the first time in nature. Among them, compounds 1-3 bear an unusual anthra[2,3-b]furan-9,10-dione nucleus, 4 and 5 possess a rare 3-methyl-1H-pyrrol-2-yl substituent, and 6 and 7 are new framework anthraquinones bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. Interestingly, the in vivo assays indicated that 1, 4 and 5 had inactivation effects against tobacco mosaic virus (TMV) with inhibition rates of 41.6%, 55.4% and 38.6%, respectively, at a concentration of 50 µg/mL, which were better than that of the positive control agent, ningnanmycin (33.8%). Compounds 1, 4 and 5 also had protective effects with inhibition rates of 48.7%, 60.2% and 43.5% at the same concentration, while 4 had a better curative effect than ningnanmycin at a concentration of 100 µg/mL. In addition, mechanistic studies also revealed that a potent direct effect on TMV, the induction of SAR in tobacco plants, and the effective regulation of defense enzymes, defense genes, and defense hormones may be the reasons for the significant effects of 4 against TMV. At the same time, downregulation of the expression of total NtHsp70 protein by inhibiting the related Hsp70 genes may also be involved in tobacco resistance to TMV. To evaluate whether compounds have broader antiviral activities, the antirotavirus activities of new isolates were also evaluated and found to be highly effective with a therapeutic index (TI) value ranging from 11.6 to 17.7. This study suggests that the above anthraquinone compounds, particularly 4, have broad spectrum antiviral activities. The successful isolation and structure identification of the above anthraquinones provide new materials for the screening of anti-TMV agents and contribute to the improved utilization of N. tabacum-derived fungi.
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Aspergillus oryzae , Vírus do Mosaico do Tabaco , Nicotiana , Antraquinonas/farmacologia , Bioensaio , Antivirais/farmacologiaRESUMO
Rheum tanguticum (Rh. tanguticum) is a Chinese medicinal plant traditionally used in the treatment of constipation. As a byproduct, the seeds of this plant are rich in nutrients and phytochemicals. This study aimed to determine and assess seed germination ability, seed physical characteristics, soluble protein content, chemical constituents and antioxidant capacity from different breeding lines, to promote the development and utilization of seed resources. Significant differences were observed for the soluble protein content and antioxidant assays among the ten lines. The contents of aloe-emodin, rhein and catechins accumulated in seeds were extremely low and significantly different from those in roots. In contrast, emodin and chrysophanol were abundant in seeds, and significant differences were observed between seeds and roots. It was found that associations between gallic acid and catechins were not significant for either soluble protein or antioxidant capacity. There was a significantly positive correlation between the contents of four anthraquinones (aloe-emodin, rhein, emodin and chrysophanol) and soluble protein. Seeds have potent antioxidative capacity and relatively high levels of soluble protein content. The rich chemical composition of seeds can be widely used in the medical industry for further development.
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Antioxidantes , Rheum , Antraquinonas/farmacologia , Antraquinonas/química , Antioxidantes/farmacologia , Emodina , Rheum/química , Sementes/química , TibetRESUMO
INTRODUCTION: Solid-phase extraction applied to plant matrices is nowadays a well-validated technique allowing to concentrate and purify different secondary metabolites. Several classes of phytochemicals have been selectively extracted by this methodology. During the last decade attention has been focused on biologically active anthraquinones from numerous sources like edible, healthy, and medicinal plants. OBJECTIVES: The aim of this review is to provide a detailed literature survey of the solid-phase adsorption methodologies for the extraction of natural anthraquinones reported so far and to discuss and propose future directions in this field of research. MATERIALS AND METHODS: Substructure search was performed in the SciFinder Scholar, PubMed, Medline, and Scopus databases. RESULTS: The first report about application of solid-phase adsorption for the purification of anthraquinones appeared in the literature in 2002. From this date, and in particular during recent years, the most notable examples included the use of chitin- and chitosan-based polymers, of molecularly imprinted polymers, of coated magnetic nanoparticles, of miniaturized matrix solid-phase dispersion, of functionalized resins, of differently structured lamellar solids, and finally of vortex-synchronized matrix solid-phase dispersion. CONCLUSIONS: The herein detailed solid-phase adsorption methodologies are powerful tools to selectively extract natural anthraquinones and/or provide anthraquinone-enriched phytopreparations. Nevertheless, many other important methods have been applied to synthetic anthraquinones (e.g., azo dyes). These could be conveniently employed also for natural anthranoids. Studies in this field are discussed in this review article.
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Impressão Molecular , Adsorção , Extração em Fase Sólida/métodos , Polímeros/química , AntraquinonasRESUMO
Chemical investigation of roots of the plant, Rubia cordifolia Linn, led to the isolation of an undescribed anthraquinone, cordifoquinone R, determined as 1,2-dihydroxy-6-methoxyanthracene-9,10-dione (6) based on the 1D and 2D NMR analyses and HRESIMS. Ten other known compounds viz.1,4-dihydroxy-2-methoxyanthracene-9,10-dione (1), rubiadin (2), xanthopurpurin (3), 1-methoxy-3-hydroxy-2-carbomethoxy-9,10-anthraquinone (4), alizarin (5), ß-sitosterol glucoside (7), scopoletin (8), oleanolic acid, (9), pomolic acid (10), queretaroic acid (11) were also isolated. Out of these compounds, 4, 10, and 11 are first reported from this plant species. Compounds 2, 3, 6, 7, and 10 showed activity in the range of 16-32 µg/ml against S. aureus ATCC 29213.
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Anti-Infecciosos , Rubia , Triterpenos , Rubia/química , Triterpenos/farmacologia , Staphylococcus aureus , Anti-Infecciosos/farmacologia , Antraquinonas/farmacologia , Antraquinonas/químicaRESUMO
Marine biofouling is the undesired accumulation of organic molecules, microorganisms, macroalgae, marine invertebrates, and their by-products on submerged surfaces. It is a serious challenge for marine vessels and the oil, gas, and renewable energy industries, as biofouling can cause economic losses for these industries. Natural products have been an abundant source of therapeutics since the start of civilisation. Their use as novel anti-fouling agents is a promising approach for replacing currently used, harmful anti-fouling agents. Anthraquinones (AQs) have been used for centuries in the food, pharmaceutical, cosmetics, and paint industries. Citreorosein and emodin are typical additives used in the anti-fouling paint industry to help improve the global problem of biofouling. This study is based on our previous study, in which we presented the promising activity of structurally related anthraquinone compounds against biofilm-forming marine bacteria. To help uncover the anti-fouling potential of other AQ-related structures, 2194 compounds from the COCONUT natural products database were analysed. Molecular docking analysis was performed to assess the binding strength of these compounds to the LuxP protein in Vibrio carchariae. The LuxP protein is a vital binding protein responsible for the movements of autoinducers within the quorum sensing system; hence, interrupting the process at an early stage could be an effective strategy. Seventy-six AQ structures were found to be highly docked, and eight of these structures were used in structure-based pharmacophore modelling, resulting in six unique pharmacophore features.
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Incrustação Biológica , Produtos Biológicos , Incrustação Biológica/prevenção & controle , Simulação de Acoplamento Molecular , Biofilmes , Produtos Biológicos/farmacologia , Antraquinonas/farmacologiaRESUMO
Emodin-8-O-glucoside (E-8-O-G) is a glycosylated derivative of emodin that exhibits numerous biological activities, including immunomodulatory, anti-inflammatory, antioxidant, hepatoprotective, or anticancer activities. However, there are no reports on the activity of E-8-O-G against cancers of the nervous system. Therefore, the aim of the study was to investigate the antiproliferative and cytotoxic effect of E-8-O-G in the SK-N-AS neuroblastoma, T98G human glioblastoma, and C6 mouse glioblastoma cancer cells. As a source of E-8-O-G the methanolic extract from the aerial parts of Reynoutria japonica Houtt. (Polygonaceae) was used. Thanks to the application of centrifugal partition chromatography (CPC) operated in the descending mode using a mixture of petroleum ether:ethyl acetate:methanol:water (4:5:4:5 v/v/v/v) and a subsequent purification with preparative HPLC, E-8-O-G was obtained in high purity in a sufficient quantity for the bioactivity tests. Assessment of the cancer cell viability and proliferation were performed with the MTT (3-(bromide 4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium), CTG (CellTiter-Glo®) and BrdU (5-bromo-2'-deoxyuridine) assays, respectively. E-8-O-G inhibits the viability and proliferation of SK-N-AS neuroblastoma, T98G human glioblastoma multiforme, and C6 mouse glioblastoma cells dose-dependently. E-8-O-G seems to be a promising natural antitumor compound in the therapy of nervous system tumors.
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Emodina , Glioblastoma , Neoplasias do Sistema Nervoso , Neuroblastoma , Animais , Camundongos , Humanos , Glucosídeos/farmacologia , Glioblastoma/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/químicaRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and has become a huge public health issue worldwide. Inhibition of nucleotide oligomerization domain-like receptors containing pyrin domain 3 (NLRP3) inflammasome is a potential therapeutic strategy for NAFLD. Currently, there are no drugs targeting NLRP3 inflammasome for clinical treatment of NAFLD. In this study, we explored the efficacy and mechanism of rhubarb free anthraquinones (RFAs) in treating NAFLD by inhibiting NLRP3 inflammasome. METHODS: First, NLRP3 inflammasome was established in mouse bone marrow-derived macrophages (BMDMs), Kuffer cells and primary hepatocytes stimulated by lipopolysaccharide (LPS) and inflammasome inducers to evaluate the effect of RFAs on inhibiting NLRP3 inflammasome and explore the possible mechanism. Further, Mice NAFLD were established by methionine and choline deficiency diet (MCD) to verify the effect of RFAs on ameliorating NAFLD by inhibiting NLRP3 inflammasome. RESULTS: Our results demonstrated that RFAs including rhein/diacerein, emodin, aloe emodin and 1,8-dihydroxyanthraquinone inhibited interleukin-1 beta (IL-1ß) but had no effect on tumor necrosis factor-alpha (TNF-α). Similar results were also showed in mouse primary hepatocytes and Kuffer cells. RFAs inhibited cleavage of caspase-1, formation of apoptosis-associated speck-like protein containing a CARD (ASC) speck, and the combination between NLRP3 and ASC. Moreover, RFAs improved liver function, serum inflammation, histopathological inflammation score and liver fibrosis. CONCLUSIONS: RFAs including rhein/diacerein, emodin, aloe emodin and 1,8-dihydroxyanthraquinone ameliorated NAFLD by inhibiting NLRP3 inflammasome. RFAs might be a potential therapeutic agent for NAFLD.
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Emodina , Hepatopatia Gordurosa não Alcoólica , Rheum , Animais , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Rheum/metabolismoRESUMO
BACKGROUND: Aloe vera (Aloe barbadensis Miller), commonly known as Ghritkumari/Gwarpatha, is a member of the Liliaceae family, used in the traditional medicine system for ages. Aloe vera has made its importance as a therapeutic agent, acting as a cure for various diseases such as skin problems, lungs, and heart disorders, diabetes, ulcers, various microbial infections, and asthma. Despite its tremendous health benefits, the dark side of the plant is a reason of concern as there are several active compounds present in the plant, raising questions on its safe oral consumption and application. METHODS AND RESULTS: The literature review was compiled from information resourced from various national and international journals available at Google Scholar and curated with Mendeley. The data mining was carried out during the period of January to May 2021. This study explored and summarized the dark side of Aloe vera, subjected to various secondary metabolites present in it. Aloin, the most active compound of Aloe vera, is a type of anthraquinone metabolized by human gut microflora, resulting in the formation of aloe-emodin anthraquinone, later being associated with several harmful effects such as carcinogenicity, genotoxicity, nephrotoxicity, and purgative. Besides this, several alkaloids and polysaccharides present in the plant are reported to cause hepatotoxicity and male infertility, respectively. CONCLUSIONS: The harmful effects of the plants are not adequately discovered yet; hence there is a need to come up with some mechanism to understand and suppress the formation of such toxic compounds completely. This review examined the botany, active compounds, and adverse clinical effects in the range of metabolites associated with this herb - "Aloe vera".
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Aloe , Antraquinonas , Dano ao DNA , Humanos , Masculino , Extratos Vegetais/efeitos adversos , PolissacarídeosRESUMO
The scientific community has found deep interest in anthraquinone-based compounds due to their therapeutic properties and challenging structural elements. Various architecturally beautiful natural products have been successfully synthesized in recent decades utilizing two main strategies: either an early-stage synthesis of the anthraquinone and further elongation of the system, or a late-stage introduction of the anthraquinone ring moiety. Select syntheses of complex anthraquinone monomers and dimers within the past 20 years are described with an emphasis on the retrosynthetic disconnections that shape the anthraquinone-installation strategy.