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Hodgsonia heteroclita subsp. indochinensis, a member of the Cucurbitaceae family, is utilized in traditional medicinal remedies based on indigenous wisdom. This study aimed to comprehensively identify and analyze the bioactive phytoconstituents within H. heteroclita subsp. indochinensis seeds. Seeds were sequentially extracted with n-hexane, ethyl acetate, and methanol. Liquid chromatography-mass spectrometry analysis detected ferulic acid, salicylic acid, cucurbitacin E, stigmasterol glucoside, and ß-sitosterol glucoside in all extracts. The total phenolic content in the HH(S)-EtOAc and HH(S)-MeOH was 14.22 ± 1.58 and 12.98 ± 1.03 mg gallic acid equivalent/g, respectively. Consequently, the HH(S)-EtOAc demonstrated antioxidant activity with an IC50 of 1.10 ± 0.28 mg/mL, while the HH(S)-MeOH displayed strong antioxidant potential with an IC50 of 0.04 ± 0.00 mg/mL according to an ABTS assay. Antibacterial evaluations of both the HH(S)-hexane and HH(S)-EtOAc revealed significant activity against Staphylococcus aureus (zone of inhibition (ZOI): 13.67 ± 2.31 and 11.67 ± 1.53 mm, respectively) but limited activity against Escherichia coli (ZOI: 7.33 ± 0.58 and 7.67 ± 0.58 mm, respectively). Additionally, the extracts exhibited low minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values, ranging from 62.50 to 250 mg/mL. The antiproliferative activity of seed extracts was assessed against two breast cancer cell lines (MCF-7 and MDA-MB-231), normal breast cells (MCF10A), and human embryonic kidney (HEK) 293T cells, through MTT and clonogenic assays. The results revealed IC50 values exceeding 400 µg/mL, indicating that the extracts are safe. Furthermore, all seed extracts (50 µg/mL) exhibited potent anti-inflammatory activity, evident by their substantial inhibition of nitric oxide production (p < 0.001) and inducible nitric oxide synthase (iNOS) gene expression (p < 0.05) in LPS-induced RAW264.7. These findings demonstrate the potential for H. heteroclita subsp. indochinensis seed extracts in the development of functional foods, nutraceuticals, and dietary supplements due to their diverse bioactive compounds and substantial biological activities, particularly their anti-inflammatory effects.
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Two series of urolithin derivatives, totally 38 compounds, were synthesized. Their anti-inflammatory activity was investigated by detecting the inhibitory effects on the expression of TNF-α in bone marrow-derived macrophages (BMDMs), showing that 24 of 38 ones reduced the expression of TNF-α. Compound B2, the ring C opened derivative of urolithin B with a butoxycarbonyl substitution in ring A, showed the strongest inhibitory activity compared with that of indomethacin. Furthermore, B2 treatment decreased the expression of pro-inflammatory factors IL-1ß, IL-6, iNOS and COX-2. Mechanically, the anti-inflammatory effect of B2 was related to the inhibition of NF-κB signaling pathway. These results clearly illustrated that B2 hold potential for application as an anti-inflammatory agent. The present study provided a viable approach to modify the gut metabolites for anti-inflammatory drug development.
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Inflamação , Fator de Necrose Tumoral alfa , Humanos , Fator de Necrose Tumoral alfa/metabolismo , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Transdução de Sinais , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/uso terapêuticoRESUMO
The pro-inflammation activity of litchi thaumatin-like protein (LcTLP) led to be responsible for the occurrence of adverse reactions after excessive consumption of litchi. This study aimed to characterize the changes in the structure and inflammatory activity of LcTLP induced by ultrasound treatment. Significant molecular structure of LcTLP changes occured at 15 min ultrasound treatment, and then tended to recover with subsequent treatment. Secondary structure (α-helices decreased from 17.3% to 6.3%), tertiary structure (the maximum endogenous fluorescence intensity decreased), and microstructure (mean hydrodynamic diameter reduced from 4 µm to 50 nm) of the LcTLP treated for 15 min (LT15) were significantly affected, which led to the inflammatory epitope of LcTLP (domain II and V-cleft) unfolded. In vitro, LT15 had a significant anti-inflammatory response, which inhibited NO production and had the best effect at 50 ng/mL in RAW264.7 macrophages (73.24%). Moreover, proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secretion and mRNA expression levels were also significantly lower compared with untreated LcTLP (p < 0.05). Western blot further confirmed that the expressions of IκB-α, p65, p38, ERK and JNK reduced markedly (p < 0.05), which indicated LT15 inhibited the inflammatory response through NF-κB and MAPK transduction pathways. Overall, it can be hypothesized that LT15 exposed to low frequency ultrasonic fields have a direct effect on the protein surface structure and thus on the entry of LT15 into cells, making 15-minute ultrasound treatment potentially useful in reducing the pro-inflammatory properties of litchi or related liquid products.
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Litchi , NF-kappa B , NF-kappa B/metabolismo , NF-kappa B/farmacologia , Transdução de Sinais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Ultrassom , Macrófagos , Citocinas/metabolismo , Citocinas/farmacologiaRESUMO
This study was conducted to evaluate the effects of different artificial light sources on the growth characteristics and various biological activities of the Atractylodes macrocephala x Atractylodes japonica hybrid cv. 'Dachul', which is highly useful for medicinal purposes. The plant had the largest biomass with a plant height of 38.20 ± 1.95 cm when treated with microwave electrodeless light (MEL). The chlorophyll content of the plants treated with fluorescent light (FL) was 53.93 ± 1.05 SPAD and was the highest. The antioxidant effect, determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), was the highest with 92.7 ± 0.2% in plants treated with light-emitting diode (LED)-green light. Total phenol and flavonoid contents were significantly higher with 19.7 ± 0.5 mg GAE/g and 40.2 ± 2.2 mg QE/g in the sample treated with LED-green light, respectively. For antimicrobial activity using the minimum inhibitory concentration (MIC) technique, the inhibitory ability against Escherichia coli was at 0.25 mg/mL under LED-green light treatment. The whitening activity using tyrosinase enzyme showed the highest tyrosinase inhibitory ability at 62.1 ± 1.2% of the above extract treated with MEL light. To confirm the immune activity in lipopolysaccharide (LPS)-induced RAW 264.7 cells, NO production of inflammation-related substances was measured. In addition, the inflammation-related genes iNOS (inducible nitric oxide synthase), COX-2 (cyclooxygenase-2), and TNF-α (tumor necrosis factor-α) in the same sample were confirmed using reverse transcriptase (RT)-PCR, and the result showed that gene expression was suppressed compared with that in the control group. It is expected that Dachul plants treated with LED-blue light will play an important role in enhancing intracellular anti-inflammatory activity. From these results, the effect for various biological activities appeared in a significantly diverse spectrum in response to different wavelengths of artificial light sources in Dachul.
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Background: Currently, there are no effective methods for assessing hepatic inflammation without resorting to histological examination of liver tissue obtained by biopsy. T2-weighted images (T2WI) are routinely obtained from liver magnetic resonance imaging (MRI) scan sequences. We aimed to establish a radiomics signature based on T2WI (T2-RS) for assessment of hepatic inflammation in people with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 203 individuals with biopsy-confirmed NAFLD from two independent Chinese cohorts with liver MRI examination were enrolled in this study. The hepatic inflammatory activity score (IAS) was calculated by the unweighted sum of the histologic scores for lobular inflammation and ballooning. One thousand and thirty-two radiomics features were extracted from the localized region of interest (ROI) in the right liver lobe of T2WI and, subsequently, selected by minimum redundancy maximum relevance and least absolute shrinkage and selection operator (LASSO) methods. The T2-RS was calculated by adding the selected features weighted by their coefficients. Results: Eighteen radiomics features from Laplacian of Gaussian, wavelet, and original images were selected for establishing T2-RS. The T2-RS value differed significantly between groups with increasing grades of hepatic inflammation (P<0.01). The T2-RS yielded an area under the receiver operating characteristic (ROC) curve (AUROC) of 0.80 [95% confidence interval (CI): 0.71-0.89] for predicting hepatic inflammation in the training cohort with excellent calibration. The AUROCs of T2-RS in the internal cohort and external validation cohorts were 0.77 (0.61-0.93) and 0.75 (0.63-0.84), respectively. Conclusions: The T2-RS derived from radiomics analysis of T2WI shows promising utility for predicting hepatic inflammation in individuals with NAFLD.
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BACKGROUND: HBV integration is suspected to be an obstinate risk factor for hepatocellular carcinoma (HCC) in the era of antiviral therapy. Integration events start to occur in the immunotolerance phase, but their fates in the immune clearance phase have not yet been clarified. Here, we report the influences of liver damage on HBV integration and clonal hepatocyte expansion in patients with chronic hepatitis B (CHB). METHODS: HBV integration breakpoints in liver biopsy samples from 54 CHB patients were detected using a modified next-generation sequencing assay. RESULTS: A total of 3729 (69 per sample) integration breakpoints were found in the human genome, including some hotspot genes and KEGG pathways, especially in patients with abnormal transaminases. The number of breakpoint types, an integration risk parameter, was negatively correlated with HBV DNA load and transaminase levels. The average, maximum and total frequencies of given breakpoint types, parameters of clonal hepatocyte expansion, were negatively correlated with HBV DNA load, transaminase levels and liver inflammation activity grade score. The HBV DNA load and inflammation activity grade score were further found to be positively correlated with transaminase levels. Moreover, nucleos(t)ide analog (NUC) treatment that normalized transaminases nonsignificantly reduced the types, but significantly increased the average frequency and negated the enrichments of integration breakpoints. CONCLUSION: Liver damage mainly removed the inventories of viral integration and clonal hepatocytes in CHB. NUC treatment may have reduced HBV integration but clearly increased clonal hepatocyte expansion, which may explain why HCC risk cannot be ruled out by NUC treatment.
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Vírus da Hepatite B , Hepatite B Crônica , Carcinoma Hepatocelular , DNA Viral/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatócitos , Humanos , Neoplasias HepáticasRESUMO
In this study, the structural characterization and anti-inflammation effect of dilute alkali-soluble polysaccharides from purple sweet potato were investigated. Three fractions (F-1, F-2 and F-3) were obtained by purifying crude polysaccharides on DEAE-52 cellulose column. The main fraction (F-1) was further purified on Sephadex G-200 column to afford purified alkali-soluble sweet potato polysaccharide (ASPP). The chemical structure of ASPP was analyzed by gas chromatography, Fourier transform infrared spectroscopy, methylation analysis and nuclear magnetic resonance spectroscopy. Monosaccharide compositional analysis showed ASPP was composed of rhamnose, arabinose, xylose, mannose and glucose in the molar ratio of 2.8:1.9:1.0:7.6:53.3. Moreover, the backbone of ASPP was composed of 1,4-linked Glcp with side chains attached to the O-6 position. The anti-inflammation effect of ASPP was further investigated by in vitro and in vivo experiments. Results showed ASPP could inhibit the levels of nitric oxide, interleukin (IL)-6, IL-1ß and TNF-α but increase the production of IL-10 in lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells. In addition ASPP could reduce the secretion of IL-6, IL-1ß and TNF-α in LPS-treated mice. Our results suggest ASPP can be developed as a novel anti-inflammation agent.
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Álcalis/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Ipomoea batatas/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Biomarcadores , Citocinas/metabolismo , Feminino , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Metilação , Camundongos , Monossacarídeos/química , Óxido Nítrico/metabolismo , Células RAW 264.7 , Solubilidade , Análise Espectral , Relação Estrutura-AtividadeRESUMO
Autoinflammatory disease (AID) is a new concept formulated from the results of studying the pathogenesis of familial periodic fevers, a heterogeneous group of genetically determined diseases characterized by causelessly recurrent exacerbations of the inflammatory process due to genetically determined disorders of innate immunity and accompanied by uncontrolled hypersecretion of interleukin-1 (IL-1). These mechanisms were a basic model for understanding a wide range of rheumatologic and other inflammatory diseases of the internal organs. The late diagnosis of AIDs and their ineffective treatment increase the risk for the development and progression of secondary AA amyloidosis. Elaboration of both clinical and effective laboratory criteria for diagnosing autoinflammation is of great importance for determining the tactics of anti-inflammatory therapy and prevention of complications.
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Doenças Autoimunes/imunologia , Inflamação/imunologia , Nefropatias/imunologia , HumanosRESUMO
Mitochondrial oxidative damage contributes to a wide range of pathologies including ischemia/reperfusion injury. Accordingly, protecting mitochondria from oxidative damage should possess therapeutic relevance. In the present study, we have designed and synthesized a series of novel indole-TEMPO conjugates that manifested good anti-inflammatory properties in a murine model of xylene-induced ear edema. We have demonstrated that these compounds can protect cells from simulated ischemia/reperfusion (s-I/R)-induced reactive oxygen species (ROS) overproduction and mitochondrial dysfunction. Furthermore, we have demonstrated that indole-TEMPO conjugates can attenuate organ damage induced in rodents via intestinal I/R injury. We therefore propose that the pharmacological profile and mechanism of action of these indole-TEMPO conjugates involve convergent roles, including the ability to decrease free radical production via lipid peroxidation which couples to an associated decrease in ROS-mediated activation of the inflammatory process. We further hypothesize that the protective effects of indole-TEMPO conjugates partially reside in maintaining optimal mitochondrial function.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Óxidos N-Cíclicos/uso terapêutico , Indóis/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/síntese química , Antioxidantes/administração & dosagem , Antioxidantes/química , Aspirina/farmacologia , Óxidos N-Cíclicos/administração & dosagem , Óxidos N-Cíclicos/síntese química , Citocromos c/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Indóis/administração & dosagem , Indóis/síntese química , Indóis/farmacologia , Intestino Delgado/irrigação sanguínea , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Mitocôndrias/metabolismo , Simulação de Dinâmica Molecular , Infiltração de Neutrófilos/efeitos dos fármacos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Anthocyanins are one of the most widespread families of natural pigments in the plant kingdom. Their health beneficial effects have been documented in many in vivo and in vitro studies. This review summarizes the most recent literature regarding the health benefits of anthocyanins and their molecular mechanisms. It appears that several signaling pathways, including mitogen-activated protein kinase, nuclear factor κB, AMP-activated protein kinase, and Wnt/ß-catenin, as well as some crucial cellular processes, such as cell cycle, apoptosis, autophagy, and biochemical metabolism, are involved in these beneficial effects and may provide potential therapeutic targets and strategies for the improvement of a wide range of diseases in future. In addition, specific anthocyanin metabolites contributing to the observed in vivo biological activities, structure-activity relationships as well as additive and synergistic efficacy of anthocyanins are also discussed.
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Antocianinas/química , Antocianinas/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose , Autofagia , Doenças Cardiovasculares/prevenção & controle , Ciclo Celular , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Transdução de SinaisRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tephrosia apollinea (Delile) DC (Leguminosae) has been used in folk medicine in Arabian countries to treat inflammatory disorders. The plant has been described to treat swelling, bone fracture, bronchitis, cough, earache and wounds. AIM OF THE STUDY: the current study aims to evaluate the anti-inflammatory properties of the major active phytoconstituent of T. apollinea and elucidate the mechanisms by which it inhibits inflammation in vitro and in vivo. MATERIAL AND METHODS: The compound, (-)-pseudosemiglabrin (SSG) was isolated as a major component from the aerial parts of T. apollinea using column chromatography techniques. Sub-chronic in vivo anti-inflammatory effect of SSG was assessed using cotton pellet granuloma assay in SD rats and serum levels of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and nitric oxide (NO) were measured, whereas, tail flick assay was performed to assess the analgesic effect of SSG. Furthermore, the anti-inflammatory effects of SSG were confirmed by measuring the levels of IL-1, TNF-α, and NO in vitro using human macrophage cell lines (U937). In addition COX inhibition assay was also conducted in cells-free system. In silico study was performed to dock SSG in cyclooxygenase enzymes and opioid receptor to predict its structure-activity and molecular mechanism. RESULTS: SSG displayed potential inhibition of granuloma tissue in rats and significantly (P<0.05) lowered the production of cytokines (TNF- α and IL-1) in vivo as well as human macrophages. Further investigation revealed that, SSG selectively inhibited COX-2 by 60% with negligible effect on COX-1. The selectivity of SSG towards COX-2 was confirmed in silico wherein, SSG demonstrated significant binding affinity with binding energy (-9.42kcal/mol). The binding found to be through covalent energy with Ser-530 amino acid residue of the active pocket of COX-2. SSG was found to prolong the flick tail time in mice by two folds. Further computational studies reveal that SSG binds to opioid receptor (µ-OR) through Ile-144 and Thr-218 with affinity two folds compared to the reference compounds, codeine and aspirin. CONCLUSION: In the present study the major phytoconstituent (-)-pseudosemiglabrin (SSG) from the aerial parts of T. apollinea demonstrated potent anti-inflammatory effect by inhibiting of granuloma tissue in rats and prolonging the tail flick time in mice. Investigation of levels of pro-inflammatory cytokines in SSG-treated rats and human macrophages demonstrated that SSG significantly inhibited TNF-α and IL-1. Also SSG showed selective inhibitory effect towards COX-2. In silico study exhibited pronounced binding affinity between SSG and µ-opioid receptor better than that of codeine and aspirin. The obtained results justify the use of aerial parts of T. apollinea to treat various inflammatory diseases and indicate that (-)-pseudosemiglabrin has a great potential to be further developed as a promising anti-inflammatory drug.
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Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Tephrosia/química , Analgésicos/farmacologia , Animais , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Técnicas In Vitro , Interleucina-1/antagonistas & inibidores , Interleucina-1/biossíntese , Lipopolissacarídeos/toxicidade , Masculino , Simulação de Acoplamento Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Six new cyanoglucosides, 2S-cardiospermin-5-benzoate (1), 2R-cardiospermin-5-p-hydroxybenzoate (2), 2S-cardiospermin-5-cis-p-coumarate (3), isocardiospermin-5-p-hydroxybenzoate (4), sutherlandin-5-p-hydroxybenzoate (5), and sutherlandin-5-cis-p-coumarate (6), together with 17 known compounds were isolated from Sorbaria sorbifolia. The structures of the new compounds were elucidated by extensive spectroscopic methods, including 1D and 2D NMR, HR-ESI-MS and ECD experiments. The biosynthetic relationship of 1-9 was also discussed. The cyanoglucosides (1-9) and 15 exhibited moderate inhibitory effect on nitric oxide production of RAW264.7 macrophages stimulated by lipopolysaccharide (LPS).
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Glicosídeos/química , Hidroxibenzoatos/química , Leucina/química , Rosaceae/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Ácidos Cumáricos/química , Ácidos Cumáricos/isolamento & purificação , Glicosídeos/isolamento & purificação , Hidroxibenzoatos/isolamento & purificação , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Componentes Aéreos da Planta/química , Células RAW 264.7RESUMO
UNLABELLED: Context Murraya paniculata (L.) Jack (Rutaceae), Qianlixiang in Chinese, is distributed in China. As an important traditional Chinese medicine (TCM), it demonstrates many bioactivities, such as febrifuge, astringent, anti-dysenteric, and tonic. OBJECTIVE: The objective of this study is to evaluate the anti-inflammatory effect of three flavonoids isolated from M. paniculata in lipopolysaccharide (LPS)-activated murine macrophage cell line and ethanol-induced gastric damage on gastric epithelial cell (GES-1). Materials and methods Three identified flavonoids were isolated from stems and leaves of M. paniculata using ultra performance liquid chromatography (UPLC). Cell viability was measured with MTT, mouse peritoneal macrophages and GES-1 cells were incubated with 0, 0.01, 0.1, 1, 10, and 100 µM P1, P3 and P8 for 24, 48, and 72 h. The inhibitory effect of pretreatment with various concentrations of 5,7,3',4',5'-pentamethoxyflavone (P1), 5,7,3',4'-tetramethoxyflavone (P3), or 5-desmethylnobiletin 5-hydroxy-6,7,8,3',4'-pentameth-oxyflavone (P8) ranging from 0.03 to 30 µM on nitric oxide (NO) secretion was quantified by the Griess assay for 24 and 48 h, while interleukin-6 (IL-6) was measured by ELISA for 24 and 48 h. Results The effects of P1, P3, and P8 on mouse peritoneal macrophages and GES-1 cells were not attributable to cytotoxic effects at the doses of 0-10 µM. The IC50 value of P1 is 53.40 µM, P3 is 120.98 µM, and P8 is 10.73 µM. The concentration of the three flavonoids had the best effects of anti-inflammation upon NO inhibition at the dose of 3 µM. P3 had the highest inhibition on IL-6 production. The GES-1 cells pretreated with three flavonoids showed a significant increase in the level of NO (P1: 7.94 ± 0.0635 µM, P3: 8.81 ± 0.0159 µM, and P8: 8.51 ± 0.0522 µM) at 24 h and a more significant increase at 48 h (P1: 9.34 ± 0.0975 µM, P3: 11.9 ± 0.0672 µM, and P8: 9.34 ± 0.0454 µM). Discussion and conclusion The current results suggested that the anti-inflammatory activity of three flavonoids was mainly manifested in the reduction of production of NO and IL-6 production. Analysis of the structure-activity relationship indicated that the double bond at C2-C3 and the position of the B ring at C2/C3 seemed to be indispensable for the anti-inflammatory activity.
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Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Murraya , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Células Epiteliais , Flavonoides/isolamento & purificação , Mucosa Gástrica/metabolismo , Macrófagos/metabolismo , Camundongos , Extratos Vegetais/isolamento & purificaçãoRESUMO
To investigate the anti-cancer properties of soil-borne actinobacteria, MJM 8637, the glutathione S-transferase pi (GST-pi) assay, anti-tumor necrosis factor (TNF)-α assay, the level of antioxidant potential by DPPH radical scavenging activity, NO scavenging activity, and ABTS radical scavenging activity in ethyl acetate extract were determined. The 16S rDNA sequencing analysis revealed that Streptomyces sp. strain MJM 8637, which was isolated from Hambak Mountain, Korea, has 99.5% similarity to Streptomyces atratus strain NBRC 3897. The physiological and the morphological characteristics of the strain MJM 8637 were also identified. The ethyl acetate extract of MJM 8637 inhibited TNF-α production approximately 61.8% at concentration 100 µg/ml. The IC50 value of the strain MJM 8637 extract on GST-pi was identified to be 120.2 ± 1.6 µg/ml. In DPPH, NO, and ABTS radical scavenging assays, the IC50 values of the strain MJM 8637 extract were found to be 977.2 µg/ml, 1143.7 µg/ml, and 454.4 µg/ml, respectively. The ethyl acetate extract of the strain MJM 8637 showed 97.2 ± 1.3% of cell viability at 100 µg/ml in RAW 264.7 cell viability assay. The results obtained from this study suggest that the ethyl acetate extract of Streptomyces sp. strain MJM 8637 could be considered as a potential source of drug for the cancers that have multidrug resistance with its GST-pi inhibition and anti-inflammation activities, and low cytotoxicity.
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The presence of endotoxin in water environments may pose a serious public health hazard. We investigated the effectiveness of advanced oxidative processes (AOP: O3/H2O2 and UV/H2O2) in the oxidative degradation of endotoxin. In addition, we measured the release of endotoxin from Escherichia coli following typical disinfection methods, such as chlorine, ozone alone and UV, and compared it with the use of AOPs. Finally, we tested the AOP-treated samples in their ability to induce tumor necrosis factor alpha (TNF-α) in mouse peritoneal macrophages. The production of hydroxyl radical in AOPs showed superior ability to degrade endotoxin in buffered solution, as well as water samples from Korean water treatment facilities, with the ozone/H2O2 being more efficient compared to UV/H2O2. In addition, the AOPs proved effective not only in eliminating E. coli in the samples, but also in endotoxin degradation, while the standard disinfection methods lead to the release of endotoxin following the bacteria destruction. Furthermore, in the experiments with macrophages, the AOPs-deactivated endotoxin lead to the smallest induction of TNF-α, which shows the loss of inflammation activity, compared to ozone treatment alone. In conclusion, these results suggest that AOPs offer an effective and mild method for endotoxin degradation in the water systems.
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Endotoxinas/química , Peróxido de Hidrogênio/química , Ozônio/química , Animais , Reatores Biológicos , Endotoxinas/farmacologia , Endotoxinas/efeitos da radiação , Escherichia coli/química , Escherichia coli/efeitos dos fármacos , Radical Hidroxila/análise , Inflamação/induzido quimicamente , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/metabolismo , Raios Ultravioleta , Purificação da Água/métodosRESUMO
Patients with long-standing inflammatory bowel disease (IBD) have an increased risk for colorectal carcinoma (CRC). Earlier studies suggest that the severity of inflammation is an independent risk factor for CRC in ulcerative colitis (UC). We investigated the role of histological inflammation as a risk factor for colorectal dysplasia or CRC to better target dysplasia surveillance in IBD. By combining our hospital patient registry and pathology database between 1996 and 2008, we identified 183 IBD patients with dysplasia or CRC. The control group was collected from our registry of IBD patients. Histological severe inflammation was present in 41.4% of patients with dysplasia and in 24.1% of patients with CRC, but in only 4.3% of controls. Severe inflammation had an odds ratio (OR) of 31.8 [95% confidence interval (CI): 15.6-64.9] for dysplasia or carcinoma compared to patients with no inflammation. Among patients with mild to moderate inflammation, the OR was 2.6 (95% CI: 1.6-4.1). Disease duration increased the annual risk for dysplasia or CRC by 4.5%. Coexisting primary sclerosing cholangitis (PSC) did not elevate the risk, whereas use of thiopurines (OR = 0.09, 95% CI: 0.02-0.33) and also 5-aminosalicylic acid (OR 0.17, 95% CI: 0.017-1.01) protected against CRC. As conclusion, degree of inflammation and duration of disease cumulatively increase the risk for dysplasia and CRC. PSC was not identified as a risk factor. We demonstrated that use of thiopurines strongly protects against CRC. These results can be applied to better target dysplasia surveillance in IBD patients.
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Adenocarcinoma/epidemiologia , Neoplasias Colorretais/epidemiologia , Síndrome do Intestino Irritável/complicações , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/uso terapêutico , Estudos de Casos e Controles , Criança , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Feminino , Humanos , Inflamação/complicações , Inflamação/tratamento farmacológico , Inflamação/patologia , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/patologia , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco , Adulto JovemRESUMO
The dietary consumption of grape and its products is associated with a lower incidence of degenerative diseases such as cardiovascular disease and certain types of cancers. Most recent interest has focused on the bioactive phenolic compounds in grape. Anthocyanins, flavanols, flavonols and resveratrol are the most important grape polyphenols because they possess many biological activities, such as antioxidant, cardioprotective, anticancer, anti-inflammation, antiaging and antimicrobial properties. This review summarizes current knowledge on the bioactivities of grape phenolics. The extraction, isolation and identification methods of polyphenols from grape as well as their bioavailability and potential toxicity also are included.