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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 474-488, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812418

RESUMO

OBJECTIVE: To investigate the effect and mechanism of a novel emodin derivative YX-18 on Burkitt lymphoma (BL) cells. METHODS: MTT assay was used to detect the effect of YX-18 on the proliferation of BL cell lines CA46 and Raji. Annexin V-PE/7-AAD double staining assay was used for detecting the effect of YX-18 on the apoptosis of CA46 and Raji cells. PI/RNase staining was used to test the effect of YX-18 on CA46 and Raji cell cycle. JC-1 method was used to measure the changes of mitochondrial membrane potential after YX-18 treatment, and DAPI staining was used to detect the morphology of apoptotic cells. Western blot was used to analyze the distribution changes of NF-κB pathway protein (P65, P-P65, IκB, P-IκB) in the cytoplasm and cell nucleus, and also the expression changes of cyclin-related protein P21, CDK2, P-CDK2, Cycling D1, Cycling E1, and the apoptosis-related protein Caspase-3, Caspase-8, Caspase-9 and the proliferation-related protein C-MYC, BCL-2 by YX-18. Real-time fluorescence-quantitative PCR was used to evaluate the effects of YX-18 on mRNA levels of C-MYC and Ki-67 genes in CA46 and Raji cells, and EBNA-1 and EBER genes of EBV in Raji (EBV+) cells. RESULTS: Novel Emodin derivative YX-18 could effectively inhibit the proliferation of BL cell lines CA46 and Raji, showing a time-dependent effect (24, 48 and 72 h: rCA46=0.89, 0.75, 0.75, rRaji=0.87, 0.73, 0.64). IC50 of CA46 cells and Raji cells treated with YX-18 for 24 h was 1.77±0.04 µmol/L and 1.97±0.22µmol/L, respectively. CA46 cells and Raji cells were treated with YX-18 at concentration of 2.0 and 4.0 µmol/L for 24 h. Compared with the control group, both strains of cells showed a very significant apoptosis at the concentration of 2.0 and 4.0 µmol/L (P<0.01), showing a concentration-dependent effect (rCA46=0.99, rRaji=0.92). Moreover, the cleavaged Caspase-3, 8 and 9 proteins were activated by YX-18 into verious degrees in both two cell lines. Both the two cell lines displayed by YX-18 cell cycle arrest at G0/G1 phase (P<0.01) after exposed to YX-18 for 24 hours at the concentration of 1.0, 2.0 µmol/L in CA46 cells and at 0.5 and 1 µmol/L in Raji cells, respectively. YX-18 decreased expression level of cyclin D1, cyclin E1, CDK2, p-cdk2 proteins and increased p21Waf1/Cip1 level in CA46 and Raji cells. YX-18 significantly declined mitochondrial membrane potential in both cells at the concentration of 2.0 and 4.0 µmol/l (P<0.01) with concentration-dependent manner (rCA46=-0.96, rRaji=-0.99). Western blot tests indicated that YX-18 down-regulated nucleus P65 and intracellular cytoplasm P65, P-IκB, P-P65 protein, and upregulated intracellular IκB level with dose-dependent manner. Meanwhile, the expression level of the cell proliferation-related molecules C-MYC and BCL-2 was decreased significantly. YX-18 suppressed mRNA levels of C-MYC and Ki-67 in both cell lines, and EBNA-1 in EBV-positive Raji cells in a concentration-dependent way. CONCLUSION: The novel emodin derivative YX-18 can significantly inhibit the proliferation of Burkitt lymphoma cells, and induce the cell apoptosis and cycle arrest. The inhibitory effect of YX-18 on the proliferation of Burkitt lymphoma cells may be related with the effect of Caspase apoptosis pathway, the proliferation and apoptosis-related molecules, such as C-MYC and Ki-67, and also to the inhibition of NF-κB pathway.


Assuntos
Linfoma de Burkitt , Emodina , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Emodina/farmacologia , Humanos , NF-kappa B
2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 241-247, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33829698

RESUMO

Objective: To synthesize three kinds of metal complexes of aloe-emodin and compare the antioxidant activities of the ligands and the complexes. Methods: Three kinds of aloe emodin metal complex, the aloe-emodin-iron (Ⅱ), the aloe-emodin-copper (Ⅱ) and the aloe-emodin-magnesium (Ⅱ) complexes, were synthesized by dissolving and stirring in anhydrous ethanol solvent, and their structures were characterized. The Fe 2+-H 2O 2-methylene blue method, the diphenyl bitter hydrazine radical method (DPPH method) and other assays were used to determine the clearance effect of ligands and complexes on superoxide radicals (O 2 -•), hydroxyl radicals (•OH) and phenyl bitter hydrazine radical (DPPH•). Results: Three kinds of aloe emodin metal complex, the aloe-emodin-iron (Ⅱ), the aloe-emodin-copper (Ⅱ) and the aloe-emodin-magnesium (Ⅱ) complexes, were successfully synthesized. According to the results of structural characterization, we speculated that the aloe-emodin metal complexes were formed at the site between the two molecules of aloe-emodin and one molecule of metal ions (Fe 2+, Mg 2+, Cu 2+) via the 9 th carbonyl and 8 th hydroxyl groups of the aloe-emodin molecules. Both the complex and the ligand have clearance effects on three kinds of free radicals, and the complex showed stronger effects than its ligand ( P<0.05). Conclusion: Coordination of aloe-emodin with metal ions, such as Fe 2+, Cu 2+, and Mg 2+, could enhance the antioxidant activity of the ligand itself.


Assuntos
Aloe , Complexos de Coordenação , Emodina , Antraquinonas , Antioxidantes
3.
Int J Nanomedicine ; 16: 47-60, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33442249

RESUMO

Purpose: To study the in vitro and in vivo antitumor effects of the colloidal suspension-in situ hydrogel of emodin (EM) constructed with the self-assembling peptide RADA16-I and systematically evaluate the feasibility of the delivery system. Methods: The MTT and colony-formation assays were used to determine the viability of normal cells NCTC 1469 and tumor cells Hepa1-6. The uptake of EM in the RADA16-I-EM in situ hydrogel by tumor cells was analyzed by laser confocal microscope and flow cytometry. Flow cytometry was used to detect the cell apoptosis and cell cycle distribution. Transwell assay was used to detect the migration and invasion of tumor cells. The antitumor efficacy of the RADA16-I-EM in situ hydrogel and its toxic effects was further assessed in vivo on Hepa1-6 tumor-bearing C57 mice. Results: The results showed that the RADA16-I-EM in situ hydrogels could obviously reduce the toxicity of EM to normal cells and the survival of tumor cells. The uptake of EM by the cells from the hydrogels was obviously increased and could significantly induce apoptosis and arrest cell cycle in the G2/M phase, and reduce the migration, invasion and clone-formation ability of the cells. The RADA16-I-EM in situ hydrogel could also effectively inhibit the tumor growth and obviously decrease the toxic effects of EM on normal tissues in vivo. Conclusion: Our results demonstrated that RADA16-I has the potential to be a carrier for the hydrophobic drug EM and can effectively improve the delivery of hydrophobic antitumor drugs with enhanced antitumor effects and reduced toxic effects of the drugs on normal cells and tissues.


Assuntos
Antineoplásicos/farmacologia , Emodina/farmacologia , Hidrogéis/química , Peptídeos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Coelhos , Suspensões , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Life Sci ; 269: 119001, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33421527

RESUMO

AIMS: Osteoarthritis (OA) is a common joint disease and the main cause of disability. We sought to determine the effective concentration of emodin on chondrocytes and to identify the dosage of emodin that induces a comparable therapeutic effect with the COX-2 inhibitor drug, celecoxib that is currently used to treat OA. MATERIAL AND METHODS: In vitro experiments induced inflammation of chondrocytes by IL-1ß, and an osteoarthritis model was established in vivo by cutting rat anterior cruciate ligament. Western Blot, Real-time PCR, HE staining, Safranin O-green staining and immunohistochemistry were performed to detect MMP-3, MMP-13, ADAMTS-4, iNOS and COL2A1 on the chondrocytes or the tibial plateau. The cytokine activity and content in serum of six groups of rats were measured by kit. RESULTS: It was found that the surface layer of the cartilage was thicker and smoother after the administration of emodin. Tissue expression of MMP-3, MMP-13, ADAMTS-4 and iNOS were significantly (p < 0.05) decreased in chondrocytes and cartilage treated with different doses of emodin, and the content of COL2A1 was reversed. Emodin also significantly decreased the blood levels of COX-2 and PGE2. The effective emodin in vitro was 5 µmol/L, whereas emodin at 80 mg/kg was equivalent to celecoxib in vivo. CONCLUSION: Emodin reduces the expression of cartilage matrix degradation biomarkers, thereby reducing the degradation of cartilage matrix and protecting the knee joint cartilage. Emodin at 5 µmol/L shows the best concentration to treat chondrocytes, and the protective effect of emodin at 80 mg/kg is comparable to that of celecoxib.


Assuntos
Cartilagem Articular/patologia , Emodina/farmacologia , Matriz Extracelular/metabolismo , Articulação do Joelho/patologia , Substâncias Protetoras/farmacologia , Proteína ADAMTS4/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Ciclo-Oxigenase 2/sangue , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Emodina/administração & dosagem , Matriz Extracelular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/sangue , Óxido Nítrico Sintase Tipo II/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologia
5.
Food Chem ; 342: 128378, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33508903

RESUMO

Rheum ribes L. (Rhubarb) is one of the most important edible medicinal plants in the Eastern Anatolia region and is called "Iskin" by local people. Resveratrol and 6-O-methylalaternin were isolated from the Rhubarb for the first time in addition to well-known secondary metabolites including emodin, aloe-emodin, ß-sitosterol and rutin. The new semi-synthetic anthraquinone derivatives with the NαFmoc-l-Lys and ethynyl group were synthesized from the isolated anthraquinones emodin and aloe-emodin of Rhubarb to increase the bioactivities. Aloe-emodin derivative with NαFmoc-l-Lys shows the highest inhibition values by 94.11 ± 0.12 and 82.38 ± 0.00% against HT-29 and HeLa cell lines, respectively, at 25 µg/mL. Further, modification of the aloe-emodin with both the ethynyl and the NαFmoc-l-Lys groups showed an antioxidant activity-enhancing effect. From molecular docking studies, the relative binding energies of the emodin and aloe-emodin derivatives to human serum albumin ranged from -7.30 and -10.62 kcal/mol.


Assuntos
Antraquinonas/química , Antineoplásicos/síntese química , Resveratrol/química , Rheum/química , Antraquinonas/síntese química , Antraquinonas/isolamento & purificação , Antraquinonas/metabolismo , Antraquinonas/farmacologia , Antineoplásicos/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Emodina/química , Emodina/isolamento & purificação , Emodina/metabolismo , Emodina/farmacologia , Humanos , Simulação de Acoplamento Molecular , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Resveratrol/isolamento & purificação , Resveratrol/farmacologia , Rheum/metabolismo , Albumina Sérica/química , Albumina Sérica/metabolismo
6.
Mol Med Rep ; 23(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33300068

RESUMO

Emodin is a naturally­occurring medicinal herbal ingredient that possesses numerous pharmacological properties, including anti­inflammatory and antioxidant effects. In the present study, potential neuroprotective effects associated with the antioxidant activity of emodin were assessed in U251 cells that were subjected to ß­amyloid peptide (Aß)­induced apoptosis and in amyloid precursor protein (APP)/presenilin­1 (PS1) double­transgenic mice. U251 is a type of human astroglioma cell line (cat. no. BNCC337874; BeNa Culture Collection). In apoptotic U251 cells, 3­h emodin pre­treatment prior to 24­h Aß co­exposure improved cell viability, suppressed lactate dehydrogenase leakage and caspase­3, ­8 and ­9 activation to inhibit apoptosis. Compared with those after Aß exposure alone, emodin ameliorated the dissipation of the mitochondrial membrane potential, inhibited the over­accumulation of reactive oxygen species, enhanced the expression levels of nuclear factor­erythroid­2­related factor 2 (Nrf2), haemeoxygenase­1, superoxide dismutase 1, Bcl­2 and catalase in addition to decreasing the expression levels of Bax. In APP/PS1 mice, an 8­week course of emodin administration improved spatial memory and learning ability and decreased anxiety. Emodin was also found to regulate key components in the Nrf2 pathway and decreased the deposition of Aß, phosphorylated­τ and 4­hydroxy­2­nonenal in APP/PS1 mice. Taken together, the present data suggest that emodin may serve as a promising candidate for the treatment of Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Precursor de Proteína beta-Amiloide/metabolismo , Emodina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Presenilina-1/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Transgênicos , Fator 2 Relacionado a NF-E2/genética , Presenilina-1/genética
7.
J Sci Food Agric ; 101(2): 414-423, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32643805

RESUMO

BACKGROUND: Aloe vera is a popular medicinal plant used widely by the cosmetic, pharmaceutical, and food industries. The A. vera leaf gel, which is used mostly for its positive effects on human health, contains over 75 different bioactive compounds, including aloin. Aloin is a toxic compound, and its content in A. vera leaf gel products depends on the different cultivation conditions and especially on leaf processing. RESULTS: In this study, A. vera leaf gel products, varied in terms of leaf processing, were analyzed using liquid chromatography for their aloin content, their antioxidant activity by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation (ABTS·+ ) and the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH· ) antioxidant activity assays and their toxicity against Aliivibrio fisheri and SH-SY5Y cells. In the samples processed with industrial methods and in those filtered in the lab, the content of aloin was found below the limit (0.1 mg L-1 ) of the EU legislation however, the unprocessed and unfiltered samples were found to contain more than 10 mg L-1 . Antioxidant activity was estimated to vary from 1.64 to 9.21 µmol Trolox mL-1 for DPPH· and from 0.73 to 5.14 µmol Trolox mL-1 for ABTS·+ . Toxicity values on A. fisheri, expressed as the concentration at 50% loss of initial luminescence, ranged from 0.03 to 0.09 mg mL-1 . The cytotoxic study indicated that aloin A at low concentrations (1 and 10 µg mL-1 ) protects SH-SY5Y cells from toxicity induced by hydrogen peroxide. CONCLUSIONS: Consequently, the filtration process of A. vera leaf gels, either laboratory or industrial, resulted in aloin A content below the EU legislation detection limits. © 2020 Society of Chemical Industry.


Assuntos
Aloe/química , Antioxidantes/análise , Emodina/análogos & derivados , Preparações de Plantas/análise , Aliivibrio fischeri/efeitos dos fármacos , Antioxidantes/toxicidade , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Emodina/análise , Emodina/toxicidade , Grécia , Humanos , Extratos Vegetais/análise , Extratos Vegetais/toxicidade , Folhas de Planta/química , Preparações de Plantas/toxicidade
8.
Phytomedicine ; 79: 153328, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33007730

RESUMO

BACKGROUND: Chaiqin chengqi decoction (CQCQD) is a Chinese herbal formula derived from dachengqi decoction. CQCQD has been used for the management of acute pancreatitis (AP) in the West China Hospital for more than 30 years. Although CQCQD has a well-established clinical efficacy, little is known about its bioactive ingredients, how they interact with different therapeutic targets and the pathways to produce anti-inflammatory effects. PURPOSE: Toll-like receptor 4 (TLR4) and the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated pro-inflammatory signaling pathways, play a central role in AP in determining the extent of pancreatic injury and systemic inflammation. In this study, we screened the bioactive ingredients using a pharmacological sub-network analysis based on the TLR4/NLRP3 signaling pathways followed by experimental validation. METHODS: The main CQCQD bioactive compounds were identified by UPLC-QTOF/MS. The TLR4/NLRP3 targets in AP for CQCQD active ingredients were confirmed through a pharmacological sub-network analysis. Mice received 7 intraperitoneal injections of cerulein (50 µg/kg; hourly) to induce AP (CER-AP), while oral gavage of CQCQD (5, 10, 15 and 20 g/kg; 3 doses, 2 hourly) was commenced at the 3rd injection of cerulein. Histopathology and biochemical indices were used for assessing AP severity, while polymerase chain reaction, Western blot and immunohistochemistry analyses were used to study the mechanisms. Identified active CQCQD compounds were further validated in freshly isolated mouse pancreatic acinar cells and cultured RAW264.7 macrophages. RESULTS: The main compounds from CQCQD belonged to flavonoids, iridoids, phenols, lignans, anthraquinones and corresponding glycosides. The sub-network analysis revealed that emodin, rhein, baicalin and chrysin were the compounds most relevant for directly regulating the TLR4/NLRP3-related proteins TLR4, RelA, NF-κB and TNF-α. In vivo, CQCQD attenuated the pancreatic injury and systemic inflammation of CER-AP and was associated with reduced expression of TLR4/NLRP3-related mRNAs and proteins. Emodin, rhein, baicalin and chrysin significantly diminished pancreatic acinar cell necrosis with varied effects on suppressing the expression of TLR4/NLRP3-related mRNAs. Emodin, rhein and chrysin also decreased nitric oxide production in macrophages and their combination had synergistic effects on alleviating cell death as well as expression of TLR4/NLRP3-related proteins. CONCLUSIONS: CQCQD attenuated the severity of AP at least in part by inhibiting the TLR4/NLRP3 pro-inflammatory pathways. Its active ingredients, emodin, baicalin, rhein and chrysin contributed to these beneficial effects.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Inflamassomos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pancreatite/tratamento farmacológico , Células Acinares/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Ceruletídeo/toxicidade , Emodina/farmacologia , Flavonoides/farmacologia , Inflamassomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pancreatite/induzido quimicamente , Pancreatite/metabolismo , Pancreatite/patologia , Células RAW 264.7 , Receptor 3 Toll-Like/antagonistas & inibidores
9.
Wei Sheng Yan Jiu ; 49(5): 809-814, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33070828

RESUMO

OBJECTIVE: To establish a quantitative analysis method for sennoside A, sennoside B and physcion by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS). METHODS: The sample was extracted by methanol-2 mmol/L ammonium formate(9∶1) at 40 ℃ for 1 h. The separation was performed using Agilent Eclipse Plus C_(18 )(2. 1 mm × 50 mm, 1. 8 µm) column with gradient elution. The mobile phase was consisted of 0. 1% formic acid and methanol. Qualitative and quantitative analysis was conducted with an electrospray ionization source operated in the negative ionization(ESI~-) mode and multiple reaction monitoring(MRM) mode. RESULTS: The linear range of three compounds were from 0. 1 to 10 µg/mL with the correlation coefficients(r) above 0. 995. The spiked recoveries were in the range of 81. 9% to 114. 5% at the concentrations of 0. 02, 0. 15 and 1. 60 mg/g with relative standard devisions(RSDs) ranged from 0. 30% to 3. 43%(n=6). The detection limits of sennoside A and sennoside B were 1. 2 µg/g. The detection limit of physcion was 2. 4 µg/g. Sennoside A, sennoside B or physcion were detected in 19 out of 40 batches of samples. The content of sennoside A ranged from 0. 184 to 6. 33 mg/g and the content of sennoside B ranged from 0. 202 to 7. 23 mg/g. The content of physcion ranged from 0. 042 to 0. 79 mg/g. CONCLUSION: The method is simple, accurate and suitable for the determination of sennoside A, sennoside B and physcion.


Assuntos
Senosídeos , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Emodina/análogos & derivados
10.
Sci Rep ; 10(1): 17699, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077836

RESUMO

Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as a receptor for spike protein binding of novel coronavirus (SARS-CoV2). Since no specific medication is available to treat COVID-19, designing of new drug is important and essential. In this regard, in silico method plays an important role, as it is rapid and cost effective compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus affected patients, in the present alarming situation. In this paper five phytochemicals, which belong to flavonoid and anthraquinone subclass, have been selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. Their molecular binding sites on spike protein bound structure with its receptor have been analyzed. From this analysis, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19. Among them, the phytochemical hesperidin can bind with ACE2 protein and bound structure of ACE2 protein and spike protein of SARS-CoV2 noncompetitively. The binding sites of ACE2 protein for spike protein and hesperidin, are located in different parts of ACE2 protein. Ligand spike protein causes conformational change in three-dimensional structure of protein ACE2, which is confirmed by molecular docking and molecular dynamics studies. This compound modulates the binding energy of bound structure of ACE2 and spike protein. This result indicates that due to presence of hesperidin, the bound structure of ACE2 and spike protein fragment becomes unstable. As a result, this natural product can impart antiviral activity in SARS CoV2 infection. The antiviral activity of these five natural compounds are further experimentally validated with QSAR study.


Assuntos
Betacoronavirus/metabolismo , Peptidil Dipeptidase A/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Regulação Alostérica , Sequência de Aminoácidos , Antraquinonas/química , Antraquinonas/metabolismo , Betacoronavirus/isolamento & purificação , Sítios de Ligação , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Emodina/química , Emodina/metabolismo , Humanos , Simulação de Acoplamento Molecular , Pandemias , Peptidil Dipeptidase A/química , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Ligação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Glicoproteína da Espícula de Coronavírus/química
11.
Toxicon ; 188: 117-121, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33122156

RESUMO

Consumption of Cassia occidentalis (CO) seeds, a ubiquitously distributed weed plant, is responsible for a pathological condition known as hepato-myo-encephalopathy (HME). The toxicity of CO seeds is largely attributed to the presence of anthraquinones (AQs). Here, we report that Emodin, a CO anthraquinone, inhibits the enzymatic activity of NADPH-Quinone reductase, which is an intracellular enzyme fundamentally involved in the detoxification of quinone containing compounds. Emodin binds to the active site of the enzyme and acts as a competitive inhibitor with respect to 2, 6-Dichlorophenolindophenol, a known substrate of NADPH-Quinone reductase. Moreover, our in-vitro study further revealed that Emodin was cytotoxic to primary rat hepatocytes.


Assuntos
Emodina/toxicidade , Hepatócitos/efeitos dos fármacos , NAD(P)H Desidrogenase (Quinona)/metabolismo , Senna (Planta) , Animais , Hepatócitos/fisiologia , NAD(P)H Desidrogenase (Quinona)/antagonistas & inibidores , NADP , Intoxicação por Plantas , Quinona Redutases/antagonistas & inibidores , Ratos
12.
Am J Chin Med ; 48(6): 1315-1330, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32907362

RESUMO

Critical care medicine is a medical specialty engaging the diagnosis and treatment of critically ill patients who have or are likely to have life-threatening organ failure. Sepsis, a life-threatening condition that arises when the body responds to infection, is currently the major cause of death in intensive care units (ICU). Although progress has been made in understanding the pathophysiology of sepsis, many drawbacks in sepsis treatment remains unresolved. For example, antimicrobial resistance, controversial of glucocorticoids use, prolonged duration of ICU care and the subsequent high cost of the treatment. Recent years have witnessed a growing trend of applying traditional Chinese medicine (TCM) in sepsis management. The TCM application emphasizes use of herbal formulation to balance immune responses to infection, which include clearing heat and toxin, promoting blood circulation and removing its stasis, enhancing gastrointestinal function, and strengthening body resistance. In this paper, we will provide an overview of the current status of Chinese herbal formulations, single herbs, and isolated compounds, as an add-on therapy to the standard Western treatment in the sepsis management. With the current trajectory of worldwide pandemic eruption of newly identified Coronavirus Disease-2019 (COVID-19), the adjuvant TCM therapy can be used in the ICU to treat critically ill patients infected with the novel coronavirus.


Assuntos
Anti-Inflamatórios/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Medicina Tradicional Chinesa , Pneumonia Viral/tratamento farmacológico , Sepse/tratamento farmacológico , Artemisininas/uso terapêutico , Astragalus propinquus , Berberina/uso terapêutico , Betacoronavirus , Estado Terminal , Emodina/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Mucosa Intestinal , Microcirculação , Pandemias , Permeabilidade , Rheum , Salvia miltiorrhiza
13.
Phytomedicine ; 78: 153293, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32777486

RESUMO

BACKGROUND: Ulcerative colitis (UC) is an intricate enteric disease with a rising incidence that is closely related to mucosa-barrier destruction, gut dysbacteriosis, and immune disorders. Emodin (1,3,8-trihydroxy-6-methyl-9,10-anthraquinone, EMO) is a natural anthraquinone derivative that occurs in many Polygonaceae plants. Its multiple pharmacological effects, including antioxidant, immune-suppressive, and anti-bacteria activities, make it a promising treatment option for UC. However, its poor solubility, extensive absorption, and metabolism in the upper gastrointestinal tract may compromise its anti-colitis effects. PURPOSE: EMO was loaded in a colon-targeted delivery system using multifunctional biomedical materials and the enhanced anti-colitis effect involving mucosa reconstruction was investigated in this study. METHODS: EMO-loaded Poly (DL-lactide-co-glycolide)/EudragitⓇ S100/montmorillonite nanoparticles (EMO/PSM NPs) were prepared by a versatile single-step assembly approach. The colon-specific release behavior was characterized in vitro and in vivo, and the anti-colitis effect was evaluated in dextran sulfate sodium (DSS)-induced acute colitis in mice by weight loss, disease activity index (DAI) score, colon length, histological changes, and colitis biomarkers. The integrity of the intestinal mucosal barrier was evaluated through transwell co-culture model in vitro and serum zonulin-related tight junctions and mucin2 (MUC2) in vivo. RESULTS: EMO/PSM NPs with a desirable hydrodynamic diameter (~ 235 nm) and negative zeta potential (~ -31 mV) could prevent the premature drug release (< 4% in the first 6 h in vitro) in the upper gastrointestinal tract (GIT) and boost retention in the lower GIT and inflamed colon mucosa in vivo. Compared to free EMO-treatment of different doses in UC mice, the NPs could enhance the remedial efficacy of EMO in DAI decline, histological remission, and regulation of colitis indicators, such as myeloperoxidase (MPO), nitric oxide (NO), and glutathione (GSH). The inflammatory factors including induced nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-1ß were suppressed by EMO/PSM NPs at both mRNA and protein levels. The obtained NPs could also promote the regeneration of the mucosal barrier via reduced fluorescein isothiocyanate (FITC)-dextran leakage in the transwell co-culture model and decreased serum zonulin levels, which was demonstrated to be associated with the upregulated tight junctions (TJs)-related proteins (claudin-2, occludin, and zo-1) and MUC2 at mRNA level. Moreover, the NPs could contribute to attenuating the liver injury caused by free EMO under excessive immune inflammation. CONCLUSION: Our results demonstrated that EMO/PSM NPs could specifically release EMO in the diseased colon, and effectively enhance the anti-colitis effects of EMO related to intestinal barrier improvement. It can be considered as a novel potential alternative for oral colon-targeted UC therapy by increasing therapeutic efficacy and reducing side-effects.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Emodina/farmacologia , Nanoestruturas/química , Administração Oral , Animais , Células CACO-2 , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Emodina/administração & dosagem , Emodina/efeitos adversos , Emodina/farmacocinética , Glutationa , Humanos , Concentração de Íons de Hidrogênio , Mucosa Intestinal/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Mucina-2/genética , Nanoestruturas/administração & dosagem , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ácidos Polimetacrílicos/química , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/genética , Distribuição Tecidual
14.
Zhongguo Zhong Yao Za Zhi ; 45(12): 2954-2959, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32627472

RESUMO

In this study, we aimed to establish a rat liver micro-tissue evaluation system to evaluate the hepatotoxicity of the main monomers in Polygonum multiflorum. Rat primary hepatocytes were isolated and purified by two-step in situ perfusion method to prepare hepatic parenchymal cells. The ultra-low adsorption plate and the inverted model were used to establish an in vitro hepatotoxicity evaluation system. After the system was established, the main monomer components(monanthone with emodin type, rhein, emodin, emodin-8-O-ß-D-glucopyranoside, physcion) of P. multiflorum were selected for in vitro hepatotoxicity evaluation. This study showed that the primary cells of the liver can form liver micro-tissues in the low adsorption plate method and the mold perfusion method, with good liver structure and function, which can be used to evaluate the hepatotoxicity of the drug to be tested after long-term administration. The five monomers to be tested in P. multiflorum can significantly affect the proliferation of primary liver micro-tissues in rats in a dose-and time-dependent manner. The hepatotoxic effects were as follows: monanthone with emodin type > rhein > emodin > emodin-8-O-ß-D-glucopyranoside > physcion. The results suggested that the emodin-type monoterpene and rhein might be the potential hepatotoxic components, while the metabolites of emodin-8-O-ß-D-glucoside and emodin methyl ether showed more toxic risks. The rat primary hepatocyte micro-tissue model system established in this experiment could be used to achieve long-term drug administration in vitro, which was consistent with the clinical features of liver injury caused by long-term use of P. multiflorum. The experimental results provided important information and reference on the clinical application and toxic component of P. multiflorum.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Emodina , Fallopia multiflora , Polygonum , Animais , Glucosídeos , Extratos Vegetais , Ratos
15.
Chin J Nat Med ; 18(6): 425-435, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32503734

RESUMO

Emodin (1, 3, 8-trihydroxy-6-methylanthraquinone) is a derived anthraquinone compound extracted from roots and barks of pharmaceutical plants, including Rheum palmatum, Aloe vera, Giant knotweed, Polygonum multiflorum and Polygonum cuspidatum. The review aims to provide a scientific summary of emodin in pharmacological activities and toxicity in order to identify the therapeutic potential for its use in human specific organs as a new medicine. Based on the fundamental properties, such as anticancer, anti-inflammatory, antioxidant, antibacterial, antivirs, anti-diabetes, immunosuppressive and osteogenesis promotion, emodin is expected to become an effective preventive and therapeutic drug of cancer, myocardial infarction, atherosclerosis, diabetes, acute pancreatitis, asthma, periodontitis, fatty livers and neurodegenerative diseases. This article intends to provide a novel insight for further development of emodin, hoping to reveal the potential of emodin and necessity of further studies in this field.


Assuntos
Antraquinonas/farmacologia , Antraquinonas/toxicidade , Emodina/farmacologia , Emodina/toxicidade , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Humanos , Estrutura Molecular , Casca de Planta , Raízes de Plantas
16.
Environ Toxicol ; 35(9): 922-929, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32293791

RESUMO

Excessive fluoride exposure contributes to neurotoxic effects. Emodin exhibits antioxidative functions in the central nervous system (CNS); however, its neuroprotective mechanism against fluoride remains to be elucidated. Our aim was to explore the neuroprotective efficacy and the possible mechanisms of emodin. In our study, synaptic proteins and oxidative stress damage were examined after human neuroblastoma SH-SY5Y cells were treated with high doses of NaF for 24 hours. Moreover, pretreatment with emodin was used to shed light on the neuroprotective effects in NaF-induced toxicity in SH-SY5Y cells. We found that NaF significantly lowered the protein expressions of SNAP 25, synaptophysin and PSD 95 in SH-SY5Y cells. In addition, NaF exposure increased the protein expression of p-ERK1/2 and decreased the protein expressions of Nrf2 and HO-1, as well as facilitated increasing ROS, 4-hydroxynonenal (4-HNE), and 8-Hydroxy-2'-deoxyguanosine (8-OHdG). Pretreatment with emodin significantly recovered these alterations caused by NaF. These data implied that the neuroprotective effects of emodin and pointed to the promising utilization for protecting against neurotoxicity induced by fluoride.


Assuntos
Emodina/farmacologia , Fluoretos/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Neuroblastoma/metabolismo , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/prevenção & controle , Espécies Reativas de Oxigênio/metabolismo , Sinapses/metabolismo , Sinapses/patologia , Sinaptofisina/metabolismo
17.
J Pharmacol Sci ; 143(3): 148-155, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32268968

RESUMO

Aloe vera (L.) Burm.f. is widely used as laxative drugs, cosmetics, and functional food due to a variety of therapeutic effects. However, several studies indicated a colonic carcinogenic activity of Aloe vera. But the underline mechanism has not been well clarified. This study aimed to explore the potential mechanism at the post-transcriptional level. Identification of Differential Expressed Alternative Splicing (DEAS) genes and events and the corresponding functional enrichment analyses were conducted on RKO cells after treated with Aloe vera aqueous extract and its two active components, aloin and aloesin. And RT-qPCR was conducted for validation. Results indicated that they induced 2200, 2342 and 2133 DEAS events, respectively. The GO enrichment and the COG classification results of DEAS genes showed that they were associated with transcription, as well as functions like signal transduction mechanisms. Moreover, DEAS genes related to the two colorectal cancerous pathways, Wnt and Notch pathways, were annotated. In conclusion, aloe extract, aloin and aloesin significantly regulated the DEAS profile of RKO cells. The colonic carcinogenicity of Aloe vera may due to its post-transcriptional regulatory activity through Alternative Splicing (AS) on genes, especially on Wnt-related and Notch-related key genes.


Assuntos
Aloe , Processamento Alternativo/efeitos dos fármacos , Processamento Alternativo/genética , Carcinogênese/induzido quimicamente , Cromonas/efeitos adversos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Emodina/análogos & derivados , Glucosídeos/efeitos adversos , Extratos Vegetais/efeitos adversos , Processamento Pós-Transcricional do RNA/efeitos dos fármacos , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Emodina/efeitos adversos , Humanos
18.
Food Chem ; 318: 126478, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32126466

RESUMO

With people's increasing needs for health concern, rutin and emodin in tartary buckwheat have attracted much attention for their antioxidant, anti-diabetic and reducing weight function. However, the biosynthesis of rutin and emodin in tartary buckwheat is still unclear; especially their later glycosylation contributing to make them more stable and soluble is uncovered. Based on tartary buckwheat' genome, the gene structures of 106 UGTs were analyzed; 21 candidate FtUGTs were selected to enzymatic test by comparing their transcript patterns. Among them, FtUGT73BE5 and other 4 FtUGTs were identified to glucosylate flavonol or emodin in vitro; especially rFtUGT73BE5 could catalyze the glucosylation of all tested flavonoids and emodin. Furthermore, the identical in vivo functions of FtUGT73BE5 were demonstrated in tartary buckwheat hairy roots. The transcript profile of FtUGT73BE5 was consistent with the accumulation trend of rutin in plant; this gene may relate to anti-adversity for its transcripts were up-regulated by MeJA, and repressed by ABA.


Assuntos
Emodina/metabolismo , Fagopyrum/genética , Glucosiltransferases/genética , Rutina/biossíntese , Acetatos/farmacologia , Ciclopentanos/farmacologia , Fagopyrum/efeitos dos fármacos , Fagopyrum/metabolismo , Flavonoides/metabolismo , Flavonóis/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genoma de Planta , Estudo de Associação Genômica Ampla , Glucosídeos/metabolismo , Glucosiltransferases/metabolismo , Oxilipinas/farmacologia , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Rutina/genética , Rutina/metabolismo
19.
Inflamm Res ; 69(4): 365-373, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32130427

RESUMO

OBJECTIVE AND DESIGN: This study aimed to investigate the anti-pulmonary inflammation effect of emodin on Wistar rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI) and RAW264.7 cells through the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway. SUBJECTS: Wistar rats and RAW264.7 cells were studied. TREATMENT: LPS was used to induce inflammation in rats or RAW264.7 cells and emodin was given once a day before LPS stimulation and continued for a certain number of days. METHODS: Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for the in vivo experiment, while cells and supernatant were collected for the in vitro experiment. Pathological changes in the lung tissues were assessed by hematoxylin and eosin staining. The levels of inflammatory factors, including TNF-α, IL-1ß, and IL-6, were determined by enzyme-linked immunosorbent assay. The expression levels of p-mTOR, HIF-1α, and VEGF proteins were measured by Western blot analysis and immunohistochemistry. The mRNA levels of p70S6K, eIF4E-BP1, and eIF4E were measured by quantitative polymerase chain reaction. RESULTS: Emodin ameliorated pathological changes and infiltrated inflammatory cells in LPS-induced ALI. It also significantly reduced the expression of inflammatory factors, including TNF-α, IL-1ß, and IL-6, in BALF and downregulated the expression of p-mTOR, HIF-1α, and VEGF proteins in the lung tissues. Similar anti-inflammatory effects and the downregulation of the mTOR/HIF-1α/VEGF signaling pathway were found in RAW264.7 cells. The mRNA levels of p70S6K, eIF4E-BP1, and eIF4E also decreased in the macrophages. CONCLUSION: Emodin alleviated LPS-induced pulmonary inflammation in rat lung tissues and RAW264.7 cells through inhibiting the mTOR/HIF-1α/VEGF signaling pathway, which accounted for the therapeutic effects of emodin on ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Emodina/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/farmacologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Emodina/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos , Células RAW 264.7 , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/imunologia , Fator A de Crescimento do Endotélio Vascular/imunologia
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