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Phytotherapy Research : PTR Aug 2016Emodin is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum... (Review)
Review
Emodin is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum multiflorum. Emodin has been used as a traditional Chinese medicine for over 2000 years and is still present in various herbal preparations. Emerging evidence indicates that emodin possesses a wide spectrum of pharmacological properties, including anticancer, hepatoprotective, antiinflammatory, antioxidant and antimicrobial activities. However, emodin could also lead to hepatotoxicity, kidney toxicity and reproductive toxicity, particularly in high doses and with long-term use. Pharmacokinetic studies have demonstrated that emodin has poor oral bioavailability in rats because of its extensive glucuronidation. This review aims to comprehensively summarize the pharmacology, toxicity and pharmacokinetics of emodin reported to date with an emphasis on its biological properties and mechanisms of action. Copyright © 2016 John Wiley & Sons, Ltd.
Topics: Emodin; Humans; Medicine, Chinese Traditional; Plant Extracts
PubMed: 27188216
DOI: 10.1002/ptr.5631 -
Theranostics 2020Anti-angiogenesis is an important and promising strategy in cancer therapy. However, the current methods using anti-vascular endothelial growth factor A (VEGFA)...
Anti-angiogenesis is an important and promising strategy in cancer therapy. However, the current methods using anti-vascular endothelial growth factor A (VEGFA) antibodies or inhibitors targeting VEGFA receptors are not as efficient as expected partly due to their low efficiencies in blocking VEGFA signaling . Until now, there is still no method to effectively block VEGFA production in cancer cells from the very beginning, i.e., from the transcriptional level. Here, we aimed to find bioactive small molecules to block VEGFA transcription. We screened our natural compound pool containing 330 small molecules derived from Chinese traditional herbs for small molecules activating the expression of seryl-tRNA synthetase (SerRS), which is a newly identified potent transcriptional repressor of VEGFA, by a cell-based screening system in MDA-MB-231 cell line. The activities of the candidate molecules on regulating SerRS and VEGFA expression were first tested in breast cancer cells. We next investigated the antiangiogenic activity by testing the effects of candidate drugs on the vascular development in zebrafish and by matrigel plug angiogenesis assay in mice. We further examined the antitumor activities of candidate drugs in two triple-negative breast cancer (TNBC)-bearing mouse models. Furthermore, streptavidin-biotin affinity pull-down assay, coimmunoprecipitation assays, docking analysis and chromatin immunoprecipitation were performed to identify the direct targets of candidate drugs. We identified emodin that could greatly increase SerRS expression in TNBC cells, consequently reducing VEGFA transcription. Emodin potently inhibited vascular development of zebrafish and blocked tumor angiogenesis in TNBC-bearing mice, greatly improving the survival. We also identified nuclear receptor corepressor 2 (NCOR2) to be the direct target of emodin. Once bound by emodin, NCOR2 got released from SerRS promoter, resulting in the activation of SerRS expression and eventually the suppression of VEGFA transcription. We discovered a herb-sourced small molecule emodin with the potential for the therapy of TNBC by targeting transcriptional regulators NCOR2 and SerRS to suppress VEGFA transcription and tumor angiogenesis.
Topics: Angiogenesis Inhibitors; Animals; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Disease Models, Animal; Emodin; Female; Gene Expression Regulation, Neoplastic; Herbal Medicine; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Mice, SCID; Neovascularization, Pathologic; Protein Kinase Inhibitors; Serine-tRNA Ligase; Vascular Endothelial Growth Factor A; Zebrafish
PubMed: 32550907
DOI: 10.7150/thno.43622 -
Pathobiology : Journal of... 2022Sepsis-associated encephalopathy (SAE) is a severe and common complication of sepsis and can induce cognitive dysfunction and apoptosis of neurons and neuroinflammation....
OBJECTIVE
Sepsis-associated encephalopathy (SAE) is a severe and common complication of sepsis and can induce cognitive dysfunction and apoptosis of neurons and neuroinflammation. Emodin has been confirmed to have anti-inflammatory effects. Thus, we sought to investigate the role of Emodin in SAE.
METHODS
The cecal ligation and puncture (CLP) method was used for the establishment of SAE in mice model. For treatment of Emodin, intraperitoneal injection of 20 mg/kg Emodin was performed before the surgery. The Morris water maze and open field tests were carried for measurement of cognitive dysfunction. Hematoxylin and eosin staining was for histological analysis of hippocampus. Cell apoptosis of hippocampus neurons was measured by TUNEL staining. Pro-inflammatory and anti-inflammatory cytokines in hippocampus tissue homogenate were evaluated by ELISA. BDNF/TrkB signaling-related proteins (TrkB, p-TrkB, and BDNF), autophagy-related proteins (LC3 II/I and Beclin-1), and apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) were detected by Western blotting.
RESULTS
Emodin significantly inhibited apoptosis and induced autophagy in hippocampal neurons of CLP-treated mice. In addition, Emodin significantly ameliorated CLP-induced cognitive dysfunction and pathological injury in mice. Meanwhile, Emodin notably inhibited CLP-induced inflammatory responses in mice via upregulation of BDNF/TrkB signaling, while the effect of Emodin was partially reversed in the presence of K252a (BDNF/TrkB signaling inhibitor).
CONCLUSION
Emodin significantly inhibited the progression of SAE via mediation of BDNF/TrkB signaling. Thus, Emodin might serve as a new agent for SAE treatment.
Topics: Animals; Apoptosis; Autophagy; Brain-Derived Neurotrophic Factor; Emodin; Hippocampus; Humans; Mice; Mice, Inbred C57BL; Receptor, trkB; Sepsis-Associated Encephalopathy
PubMed: 34872094
DOI: 10.1159/000520281 -
Drug Design, Development and Therapy 2022This study was designed to evaluate the pharmacological mechanisms of Aloin against gastric cancer (GC) via network pharmacology analysis combined with experimental...
PURPOSE
This study was designed to evaluate the pharmacological mechanisms of Aloin against gastric cancer (GC) via network pharmacology analysis combined with experimental verification.
METHODS
Using network pharmacology methods, the potential targets of Aloin and targets related to GC were screened from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the core targets and pathways of Aloin against GC. The expressions of major targets predicted by network pharmacology in normal stomach tissues and GC tissues and their relationships with overall survival of GC were searched in GEPIA, HPA and DriverDBv3 database. The results of network pharmacology analysis were verified by in vitro experiments.
RESULTS
A total of 129 potential targets were retrieved by searching the intersection of Aloin and GC targets. PPI network analysis indicated that 10 targets, including AKT1 and CASP3, were hub genes. GO enrichment analysis involved 93 biological processes, 19 cellular components, and 37 molecular functions. KEGG enrichment analysis indicated that the anti-cancer effect of Aloin was mediated through multiple pathways, such as PI3K-AKT, FoxO and Ras signaling pathway. Among them, the PI3K-AKT signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of GC. The validation of key targets in GEPIA, HPA and DriverDBv3 database showed that the verification results for most core genes were consistent with this study. Then, the results of in vitro experiment indicated that Aloin could inhibit proliferation of NCI-N87 cells and induce cell apoptosis. The results also showed that Aloin could decrease the mRNA and protein expressions of PI3K and AKT, suggesting that Aloin can treat GC by inducing cell apoptosis and regulating the PI3K-AKT signaling pathway.
CONCLUSION
This study identified the potential targets of Aloin against GC using network pharmacology and in vitro verification, which provided a new understanding of the pharmacological mechanisms of Aloin in treatment of GC.
Topics: Emodin; Humans; Molecular Docking Simulation; Network Pharmacology; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Stomach Neoplasms
PubMed: 35757520
DOI: 10.2147/DDDT.S360790 -
International Journal of Molecular... Oct 2018The anti‑inflammatory effects of aloin, a bioactive ingredient extracted from Aloe vera, have been described previously. The present study aimed to assess these...
The anti‑inflammatory effects of aloin, a bioactive ingredient extracted from Aloe vera, have been described previously. The present study aimed to assess these effects and explore the underlying molecular mechanisms. RAW264.7 cells were incubated with different doses of aloin (100, 150 and 200 µg/ml) and lipopolysaccharide (LPS; 100 ng/ml) for the indicated times. Then, inducible nitric oxide synthase (iNOS) and cyclooxygenase‑2 expression levels were detected by western blot analysis and reverse transcription polymerase chain reaction (RT‑PCR).The concentrations of inflammatory cytokines in the cell culture supernatant were determined by ELISA. Total nitric oxide (NO) assay and reactive oxygen species (ROS) kits were used to detect NO and ROS levels, respectively. Mitogen‑activated protein kinase, nuclear factor κB and Janus kinase‑signal transducer and activator of transcription (JAK‑STAT) pathway activation were verified by western blot analysis. Confocal and nucleocytoplasmic separation experiments were used to detect STAT nuclear translocation. It was identified that aloin decreased the level of LPS‑induced iNOS expression, inhibiting the release of interleukin (IL)‑1β, IL‑6, tumour necrosis factor‑α and NO dose‑dependently. Mechanistically, aloin suppressed LPS‑induced JAK1‑STAT1/3 activation and STAT1/3 nuclear translocation. Additionally, LPS‑induced ROS production was inhibited by aloin. Collectively, these data suggest that aloin attenuated LPS‑induced inflammation by inhibiting ROS‑mediated activation of the JAK1‑STAT1/3 signalling pathway, thereby inhibiting the nuclear translocation of STAT1/3 in RAW264.7 cells. The present study provides an experimental basis for the clinical application of aloin in inflammatory‑associated diseases.
Topics: Animals; Emodin; Inflammation; Janus Kinase 1; Lipopolysaccharides; Mice; RAW 264.7 Cells; Reactive Oxygen Species; STAT1 Transcription Factor; STAT3 Transcription Factor
PubMed: 30066904
DOI: 10.3892/ijmm.2018.3796 -
Frontiers in Endocrinology 2021Adipose tissue (e.g. white, brown and brite) plays a critical role in modulating energy metabolism. Activating brown adipose tissue (BAT) and inducing browning in white...
BACKGROUND
Adipose tissue (e.g. white, brown and brite) plays a critical role in modulating energy metabolism. Activating brown adipose tissue (BAT) and inducing browning in white adipose tissue (WAT) has been proposed to be a potential molecular target for obesity treatment. Emodin is a natural anthraquinone derivative that exhibits variety of pharmacologic effects including lowering lipids and regulating glucose utilization. However, the underlying mechanism of action is still unclear. In the present study, we investigated whether emodin could alleviate obesity promoting browning process in adipose tissue.
METHODS
C57BL/6J mice were fed with high fat diet to induce obesity. Emodin at the doses of 40 and 80 mg/kg were orally given to obesity mice for consecutive 6 weeks. Parameters including fasting blood glucose, oral glucose tolerance, blood lipids, and the ratios of subcutaneous white adipose tissue (scWAT) or BAT mass to body weight, and morphology of adipose tissue were observed. Besides, the protein expression of uncoupling protein 1 (UCP1) and prohibitin in BAT and scWAT was determined by immunohistochemistry method. Relative mRNA expression of , transmembrane protein 26 () and in scWAT was analyzed using qRT-PCR. And the protein expression of UCP1, CD36, fatty acid transporter 4 (FATP4), peroxisome proliferator-activated receptor alpha (PPARα) and prohibitin of scWAT and BAT were analyzed using western blotting. In addition, ultra-high-performance liquid chromatography with electrospray ionization tandem mass spectrometry was utilized to detect the small lipid metabolites of scWAT and BAT.
RESULTS
Emodin decreased the body weight and food intake in HFD-induced obesity mice, and it also improved the glucose tolerance and reduced the blood lipids. Emodin treatment induced beiging of WAT, and more multilocular lipid droplets were found in scWAT. Also, emodin significantly increased markers of beige adipocytes, e.g. , and mRNA in scWAT, and UCP1, CD36, FATP4, PPARα and prohibitin protein expression in scWAT and BAT. Furthermore, emodin perturbed the lipidomic profiles in scWAT and BAT of obese mice. Emodin increased total ceramides (Cers), lysophosphatidylcholines (LPCs), lyso-phosphatidylcholines oxygen (LPCs-O), and phosphatidylethanolamines oxygen (PEs-O) species concentration in scWAT. Specifically, emodin significantly up-regulated levels of Cer (34:1), LPC (18:2), LPC-(O-20:2), PC (O-40:7), PE (O-36:3), PE (O-38:6), PE (O-40:6), and sphingolipid (41:0) [SM (41:0)], and down-regulated PC (O-38:0), PE (O-40:4), PE (O-40:5) in scWAT of obesity mice. In terms of lipid matabolites of BAT, the emodin remarkably increased the total PCs levels, which was driven by significant increase of PC (30:0), PC (32:1), PC (32:2), PC (33:4) and PC (38:0) species. In addition, it also increased species of LPCs, e.g. LPC (20:0), LPC (20:1), LPC (22:0), LPC (22:1), LPC (24:0), and LPC (24:1). Especially, emodin treatment could reverse the ratio of PC/PE in HFD-induced obese mice.
CONCLUSIONS
These results indicated that emodin could ameliorate adiposity and improve metabolic disorders in obese mice. Also, emodin could promote browning in scWAT and activate the BAT activities. In addition, emodin treatment-induced changes to the scWAT and BAT lipidome were highly specific to certain molecular lipid species, indicating that changes in tissue lipid content reflects selective remodeling in scWAT and BAT of both glycerophospholipids and sphingolipids in response to emodin treatment.
Topics: Adipose Tissue, Brown; Adipose Tissue, White; Animals; Body Weight; Diet, High-Fat; Emodin; Lipid Metabolism; Lipid Metabolism Disorders; Male; Mice; Mice, Obese; Obesity; Thermogenesis
PubMed: 34040579
DOI: 10.3389/fendo.2021.618037 -
Inflammation Apr 2022Emodin, the effective component of the traditional Chinese medicine Dahuang, has anti-inflammatory effects. However, the protective effects and potential mechanisms of...
Emodin, the effective component of the traditional Chinese medicine Dahuang, has anti-inflammatory effects. However, the protective effects and potential mechanisms of emodin are not clear. This study investigated the protective effects and potential mechanisms of emodin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in vitro and in vivo. In vivo, we designed an LPS-induced ALI rat model. In vitro, we chose the J774A.1 cell line to establish an inflammatory cellular model, and knocked down NOD-like receptor family pyrin domain containing 3 (NLRP3) using small interfering RNA. The mRNA and protein expression of NLRP3, a C-terminal caspase recruitment domain (ASC), caspase 1 (CASP1), and gasdermin D (GSDMD) in cells and lung tissues were detected by western blot and real-time quantitative polymerase chain reaction (PCR). The expression levels of interleukin 1 beta (IL-1β) and IL-18 in the serum and supernatant were determined by the enzyme-linked immunosorbent assay. The degree of pathological injury in lung tissue was evaluated by hematoxylin and eosin (H&E) staining. In vitro, we demonstrated that emodin could inhibit NLRP3 and then inhibit the expression of ASC, CASP1, GSDMD, IL-1β, and IL-18. In vivo, we confirmed that emodin had protective effects on LPS-induced ALI and inhibitory effects on NLRP3 inflammasome -dependent pyroptosis. Emodin showed excellent protective effects against LPS-induced ALI by regulating the NLRP3 inflammasome-dependent pyroptosis signaling pathway.
Topics: Acute Lung Injury; Animals; Emodin; Inflammasomes; Lipopolysaccharides; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; Rats; Signal Transduction
PubMed: 34787801
DOI: 10.1007/s10753-021-01581-1 -
Integrative Cancer Therapies 2022Gastrointestinal (GI) cancers cause one-third of all cancer-related deaths worldwide. Natural compounds are emerging as alternative or adjuvant cancer therapies given... (Review)
Review
Gastrointestinal (GI) cancers cause one-third of all cancer-related deaths worldwide. Natural compounds are emerging as alternative or adjuvant cancer therapies given their distinct advantage of manipulating multiple pathways to both suppress tumor growth and alleviate cancer comorbidities; however, concerns regarding efficacy, bioavailability, and safety are barriers to their development for clinical use. Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a Chinese herb-derived anthraquinone, has been shown to exert anti-tumor effects in colon, liver, and pancreatic cancers. While the mechanisms underlying emodin's tumoricidal effects continue to be unearthed, recent evidence highlights a role for mitochondrial mediated apoptosis, modulated stress and inflammatory signaling pathways, and blunted angiogenesis. The goals of this review are to (1) highlight emodin's anti-cancer properties within GI cancers, (2) discuss the known anti-cancer mechanisms of action of emodin, (3) address emodin's potential as a treatment complementary to standard chemotherapeutics, (4) assess the efficacy and bioavailability of emodin derivatives as they relate to cancer, and (5) evaluate the safety of emodin.
Topics: Antineoplastic Agents; Apoptosis; Emodin; Gastrointestinal Neoplasms; Humans; Signal Transduction
PubMed: 34984952
DOI: 10.1177/15347354211067469 -
Molecules (Basel, Switzerland) Oct 2022In Tartary buckwheat (), the edible parts are mainly grain and sprouts. Tartary buckwheat contains protecting substances, which make it possible for plants to survive on... (Review)
Review
In Tartary buckwheat (), the edible parts are mainly grain and sprouts. Tartary buckwheat contains protecting substances, which make it possible for plants to survive on high altitudes and under strong natural ultraviolet radiation. The diversity and high content of phenolic substances are important for Tartary buckwheat to grow and reproduce under unfriendly environmental effects, diseases, and grazing. These substances are mainly flavonoids (rutin, quercetin, quercitrin, vitexin, catechin, epicatechin and epicatechin gallate), phenolic acids, fagopyrins, and emodin. Synthesis of protecting substances depends on genetic layout and on the environmental conditions, mainly UV radiation and temperature. Flavonoids and their glycosides are among Tartary buckwheat plants bioactive metabolites. Flavonoids are compounds of special interest due to their antioxidant properties and potential in preventing tiredness, diabetes mellitus, oxidative stress, and neurodegenerative disorders such as Parkinson's disease. During the processing and production of food items, Tartary buckwheat metabolites are subjected to molecular transformations. The main Tartary buckwheat traditional food products are bread, groats, and sprouts.
Topics: Fagopyrum; Quercetin; Catechin; Antioxidants; Ultraviolet Rays; Emodin; Rutin; Flavonoids; Glycosides
PubMed: 36296694
DOI: 10.3390/molecules27207101 -
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