RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Colorectal cancer (CRC) remains a significant global health concern, and targeting inflammation has emerged as a promising approach for its prevention and treatment. Medicinal plants and phytochemicals have garnered attention for their potential efficacy against inflammation with minimal toxicity. Osmanthus fragrans var. aurantiacus Makino (O. fragrans) has a history of traditional use in Korea and China in treating various inflammation-related conditions, but its potential use for CRC has not been uncovered. AIM OF THE STUDY: This study aims to explore the potential anti-proliferative and pro-apoptotic properties of O. fragrans, focusing on its impact on CRC treatment. By investigating O. fragrans, we aim to uncover its anti-proliferative and apoptotic effects in human CRC cells, potentially paving the way for effective and well-tolerated therapeutic strategies for CRC patients. MATERIALS AND METHODS: Ethanol (EtOH) extracts of O. fragrans leaf and flower, along with specific fractions (n-hexane, ethyl acetate (EtOAc), n-butanol, and the aqueous residue) were evaluated for their anti-proliferative effects in human CRC cells using MTT assays, and compared to normal colon cells. Mechanistic insights and chemical profiling were obtained through flow cytometry, colorimetric assays, western blotting, and molecular docking, and high-performance liquid chromatography (HPLC) system. RESULTS: Both flower and leaf EtOH extracts of O. fragrans exhibited significant anti-proliferative effects in human CRC cells, with the leaf extract demonstrating higher potency. The EtOAc fraction from the leaf extract displayed the strongest anti-CRC cell proliferative effects while no cytotoxic effects in normal colon cells. Chemical profiling of these fractions identified triterpenoids as significant components in the EtOAc fractions. The leaf EtOAc fraction caused cell cycle arrest and apoptosis, accompanied by elevating intracellular reactive oxygen species and mitochondrial dysfunction in CRC cells. Additionally, it inhibited NF-κB and ERK1/2 signaling, leading to reduced COX2 expression. Notably, two triterpenoids isolated from the leaf EtOAc fraction, maslinic acid and corosolic acid, displayed potent anti-cancer activity in CRC cells without affecting normal colon cells. Corosolic acid exhibited a strong binding affinity to COX2 and reduced its expression, supporting its role in the anti-inflammatory and anti-cancer effects. CONCLUSIONS: Our findings suggest that O. fragrans, particularly its triterpenoid-rich EtOAc fraction, holds promise as a novel therapeutic agent for CRC prevention and therapy. These results provide valuable insights into the potential application of O. fragrans and its bioactive compounds in combating CRC.
Assuntos
Acetatos , Neoplasias Colorretais , Triterpenos , Humanos , NF-kappa B , Extratos Vegetais/uso terapêutico , Ciclo-Oxigenase 2 , Simulação de Acoplamento Molecular , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Inflamação/tratamento farmacológico , Etanol/farmacologia , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológicoRESUMO
The development of therapeutic interventions for diseases necessitates a crucial step known as drug screening, wherein potential substances with medicinal properties are rigorously evaluated. This process has undergone a transformative evolution, driven by the imperative need for more efficient, rapid, and high-throughput screening platforms. Among these, microfluidic systems have emerged as the epitome of efficiency, enabling the screening of drug candidates with unprecedented speed and minimal sample consumption. This review paper explores the cutting-edge landscape of microfluidic-based drug screening platforms, with a specific emphasis on two pioneering approaches: organ-on-a-chip and C. elegans-based chips. Organ-on-a-chip technology harnesses human-derived cells to recreate the physiological functions of human organs, offering an invaluable tool for assessing drug efficacy and toxicity. In parallel, C. elegans-based chips, boasting up to 60% genetic homology with humans and a remarkable affinity for microfluidic systems, have proven to be robust models for drug screening. Our comprehensive review endeavors to provide readers with a profound understanding of the fundamental principles, advantages, and challenges associated with these innovative drug screening platforms. We delve into the latest breakthroughs and practical applications in this burgeoning field, illuminating the pivotal role these platforms play in expediting drug discovery and development. Furthermore, we engage in a forward-looking discussion to delineate the future directions and untapped potential inherent in these transformative technologies. Through this review, we aim to contribute to the collective knowledge base in the realm of drug screening, providing valuable insights to researchers, clinicians, and stakeholders alike. We invite readers to embark on a journey into the realm of microfluidic-based drug screening platforms, fostering a deeper appreciation for their significance and promising avenues yet to be explored.
Assuntos
Ensaios de Triagem em Larga Escala , Microfluídica , Animais , Humanos , Caenorhabditis elegans , Avaliação Pré-Clínica de Medicamentos , Sistemas Microfisiológicos , Dispositivos Lab-On-A-ChipRESUMO
The concern about the quality of medicinal herbs is becoming important due to the poor quality of commercial products like cosmetics, functional foods, and natural medicine produced from them. However, there is a lack of modern analytical methods to evaluate the constituents of P. macrophyllus until the moment. This paper reports an analytical method based on UHPLC-DAD and UHPLC-MS/MS MRM methods to evaluate the ethanolic extracts of P. macrophyllus leaves and twigs. 15 main constituents were identified using a UHPLC-DAD-ESI-MS/MS profiling. Subsequently, a reliable analytical method was established and successfully used to quantitate the constituent's content using four marker compounds in leaf and twig extracts of this plant. The result obtained from the current study demonstrated the secondary metabolites and the variety of their derivatives in this plant. The analytical method can help evaluate the quality of P. macrophyllus and develop high-value functional materials.
RESUMO
Ilex rotunda Thunb. has been used in traditional medicine for treating rheumatoid arthritis, relieving pain and indigestion. In the present study, we isolated three new caffeic acid benzyl ester (CABE) analogs (1-3) along with eight known compounds (4-11) from the extract of I. rotunda. The absolute configuration of α-hydoxycarboxylic acid in 1 was assigned with the phenylglycine methyl ester (PGME) method. We further investigated their anti-inflammatory activities in lipopolysaccharide (LPS)-induced macrophages (RAW 264.7) cells. Among them, compounds 2-4, 7, 8, 10, and 11 suppressed the production of nitric oxide (NO), pro-inflammatory mediators. It was additionally confirmed that the anti-inflammatory effect of active compound 2 was through significant suppression of cytokines, including interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, and IL-8 in LPS-stimulated RAW 264.7 cells and colon epithelial (HT-29) cells. Western blot analysis revealed that compound 2 decreased the LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and phosphorylated extracellular regulated kinase (pERK)1/2. The following molecular docking simulations showed the significant interactions of compound 2 with the iNOS protein. These results suggested that the compound 2 can be used as potential candidate for treating inflammatory diseases such as inflammatory bowel disease (IBD).
Assuntos
Ilex , NF-kappa B , Animais , Camundongos , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Ilex/metabolismo , Simulação de Acoplamento Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Células RAW 264.7 , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/metabolismoRESUMO
Excessive production of melanin causes various dermatological disorders including hyperpigmentation. To search for anti-melanogenesis candidates from natural products, we discovered that leaves of Osmanthus fragrans var. aurantiacus (OFA) suppressed melanin production. The extract of OFA leaves and its fractions were subjected to bioactivity-guided separation by targeting active constituents and a total of four triterpenoids were obtained: 3α,24-dihydroxyurs-12-en-28 oic acid (1), pomolic acid (2), maslinic acid (3), and corosolic acid (4). Compounds 1 and 2 were isolated from this plant for the first time. All compounds were evaluated for their inhibitory activities against melanin production and tyrosinase activity. Active compounds were further investigated to understand their mechanisms of action. Results revealed that they significantly down-regulated TYRP-1 and TYRP-2 expression levels. Our results clarified the whitening property of this plant and provided evidence that active constituents of this plant possessed anti-melanogenesis effect and anti-tyrosinase activity for the first time.
Assuntos
Oleaceae , Triterpenos , Melaninas , Extratos Vegetais/farmacologia , Folhas de Planta/metabolismo , Triterpenos/farmacologia , Monofenol Mono-OxigenaseRESUMO
Valeriana jatamansi is hired as multiple remedies for treatment of insomnia, blood and circulatory disorders, asthma, dry cough, jaundice, seminal weakness, cardiac debility, and skin diseases in Vietnam. Our research discovered the phytochemical investigation of constituents from this herbal medicine resulted in the isolation of two new compounds (jatamansides A (4) and B (7)) together with 16 known ones from the whole plant. Their structures were established by using spectroscopic techniques (multinuclear and multidimensional nuclear magnetic resonance, infrared, ultraviolet-visible), mass spectrometry, hydrolysis analysis, or comparing their NMR data to those reported in the literature. In addition, all the isolates were evaluated for their inhibitory effect against TNF-α production in LPS-stimulated on RAW264.7 cells with significant inhibition.
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Plantas Medicinais , Valeriana , Anti-Inflamatórios/farmacologia , Iridoides/química , Estrutura Molecular , Plantas Medicinais/química , Valeriana/químicaRESUMO
Species of Podocarpus are used traditionally in their native areas for the treatment of fevers, asthma, coughs, cholera, chest pain, arthritis, rheumatism, and sexually transmitted diseases. To identify natural products having efficacy against inflammatory bowel disease (IBD), we identified a new, 16-hydroxy-4ß-carboxy-O-ß-D-glucopyranosyl-19-nor-totarol (4) together with three known diterpenoids from P. macrophyllus. Furthermore, all the extracts, fractions, and isolates 1-4 were investigated for their anti-inflammatory effects by assessing the expression on nitric oxide (NO) production and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 and HT-29 cells. Among them, nagilactone B (2) exhibited a potent anti-inflammatory effect against NO production on RAW 264.7 cells; therefore, nagilactone B was further assessed for anti-inflammatory activity. Western blot analysis revealed that nagilactone B significantly decreased the expression of LPS-stimulated protein, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and phosphorylated extracellular regulated kinase (pERK)1/2. In addition, nagilactone B downregulated tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 levels in LPS-induced macrophages and colonic epithelial cells. To our best knowledge, this is the first report on the inhibitory effect of nagilactone B (pure state) and rakanmakilactone G against NO production in LPS-stimulated RAW 264.7 cells. Thus, diterpenoids isolated from P. macrophyllus could be employed as potential therapeutic phytochemicals for IBD.
Assuntos
Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Mediadores da Inflamação/antagonistas & inibidores , Inflamação/tratamento farmacológico , Lipopolissacarídeos/imunologia , Traqueófitas , Animais , Anti-Inflamatórios/isolamento & purificação , Diterpenos/isolamento & purificação , Células HT29 , Humanos , Inflamação/imunologia , Mediadores da Inflamação/imunologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Camundongos , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Células RAW 264.7 , Traqueófitas/químicaRESUMO
BACKGROUND: It has recently been emphasized that the unmet needs of cancer patients should be evaluated more holistically, for example, by exploring caregivers' perspectives and cross cultural differences. This study explored additional domains or items of unmet needs among Korean cancer patients in reference to the Sheffield Profile for Assessment and Referral to Care (SPARC). METHODS: We conducted four focus group discussions (FGDs) with 15 cancer patients, following a semi-structured format to elicit participants' health perceptions, comments on SPARC, and opinions on the roles of medical professionals to improve the health-related quality of life of cancer patients. We analyzed the verbatim transcripts using a content analysis method. RESULTS: The following themes were derived: living as a cancer patient, striving to overcome cancer, changing attitudes toward life after the cancer diagnosis, and ways to live a better life as a cancer patient. The participants asserted the significance of providing adequate treatment information that is easily understood by cancer patients during the conversation between patients and medical professionals. Besides the physical symptoms identified by SPARC, the participants struggled with numbness in their hands and feet and hair loss. Korean cancer patients prominently wished to avoid burdening their family or others in their daily life. They considered the improvement of health behaviors, such as diet and exercise, as part of the treatment, which was not limited to drugs. Furthermore, it was essential to evaluate the value of cancer patients' lives, as they desired to be helpful members of their families and society. CONCLUSIONS: This study identified additional domains and items of unmet needs of Korean cancer patients and broadened the understanding of unmet needs among cancer patients.
Assuntos
Neoplasias , Qualidade de Vida , Cuidadores , Necessidades e Demandas de Serviços de Saúde , Humanos , Neoplasias/terapia , Pesquisa Qualitativa , República da CoreiaRESUMO
Siegesbeckia glabrescens (Compositae), an annual herb indigenous to Korean mountainous regions and has been eaten as a food in Korea. This study investigated ABTS, DPPH and nitric oxide (NO) radical-scavenging activities, and melanin production and TYR inhibitory effects-guided fractionation to identify therapeutic phytochemicals from S. glabrescens that can attenuate oxidation and melanogenesis in murine melanoma B16F10 cells. Nine compounds with inhibitory effects on melanin production, and TYR activity, and ABTS, DPPH, and NO radical scavenging activity were isolated from the 100% ethanol fraction from S. glabrescens. Among the nine compounds, kirenol (K), methyl ent-16α, 17-dihydroxy-kauran-19-oate (MDK) had strong inhibitory effects on melanin production and TYR activity with antioxidant effects. Western blot analysis revealed that K and MDK suppressed tyrosinase-related protein (TYRP)-1, TYRP-2 and microphthalmia-associated transcription factor (MITF) expression. Moreover, these two compounds inhibited intracellular reactive oxygen species (ROS) level in tert-butyl hydroperoxide (t-BHP)-treated B16F10 cells. Our results suggest that S. glabrescens containing active compounds such as K and MDK, which has antioxidant and antimelanogenesis effects, is the potent therapeutic and functional material for the prevention of oxidation-induced hyperpigmentation.
Assuntos
Antineoplásicos , Antioxidantes , Diterpenos , Hiperpigmentação/tratamento farmacológico , Extratos Vegetais , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Asteraceae/química , Linhagem Celular Tumoral , Diterpenos/administração & dosagem , Diterpenos/farmacologia , Melanoma Experimental , Camundongos , Fator de Transcrição Associado à Microftalmia/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
There are limited data regarding long-term safety and efficacy in cancer survivors receiving chronic opioid therapy. With conflicting recommendations on opioid-prescribing practices and lack of available outcome data, this study aimed to provide a longitudinal perspective on opioid prescribing in cancer survivors. A retrospective chart review at a comprehensive cancer care center pain clinic used data from pain clinic provider notes from 2013 to 2018. Inclusion criteria were patients in clinical remission not receiving active chemotherapy or immunotherapy and receiving opioids during the study period. Opioid dosing changes and outcomes between zero and five years were evaluated by standard statistical analysis. Thirty-two patients met inclusion criteria. Solid malignancies were more common than hematologic malignancies (72% vs. 28%). Common pain complaints were related to postsurgical changes (43%), postradiation (32%), and chemotherapy-induced pain syndromes (25%). There were no serious adverse events. One patient exhibited possible aberrant behavior. At the initial visit, the median morphine milligram equivalent per day (MME/day) was 130. Median MME/day at Year 0 (study start) and Year 5 was 135 and 159, respectively (P = 0.475). Functional status was satisfactory in 58% at Year 0 and increased to 91% of patients meeting their functional goals at Year 5. In a carefully monitored group of cancer survivors with persistent pain, chronic opioid therapy was safely managed during extended periods without significant opioid escalation or evidence of serious adverse events including aberrant behaviors. This population benefited when opioid therapy was managed with a focus on function rather than reduction of pain intensity scores.
Assuntos
Dor do Câncer , Sobreviventes de Câncer , Dor Crônica , Neoplasias , Analgésicos Opioides/efeitos adversos , Dor do Câncer/tratamento farmacológico , Dor Crônica/tratamento farmacológico , Humanos , Neoplasias/tratamento farmacológico , Dor/tratamento farmacológico , Clínicas de Dor , Manejo da Dor , Padrões de Prática Médica , Estudos RetrospectivosRESUMO
Chrysanthemum zawadskii var. latilobum (CZL) has been used in Eastern medicine for the treatment of various diseases, such as pneumonia, bronchitis, cough, the common cold, pharyngitis, bladder-related disorders, gastroenteric disorders, and hypertension. In the present study, we isolated two strong antiallergic compounds from CZL, namely, eriodictyol-7-O-ß-d-glucuronide (EDG) and 5,7-dihydroxy-4-chromene (DC), and investigated their antiallergic effects in FcεRI-mediated human basophilic KU812F cells. EDG and DC downregulated the protein and messenger RNA (mRNA) expression of FcεRI on the cell surface. Moreover, Western blotting analysis showed that EDG and DC inhibited the expression of protein tyrosine kinases such as Syk and Lyn, and extracellular-regulated kinases (ERK) 1/2. These results suggested that EDG and DC, antiallergic constituents of CZL, are potential therapeutic candidates for protection against and for the treatment of allergic disorders.
Assuntos
Antialérgicos/isolamento & purificação , Basófilos/efeitos dos fármacos , Benzopiranos/farmacologia , Chrysanthemum/química , Flavanonas/farmacologia , Glucuronatos/farmacologia , Extratos Vegetais/farmacologia , Antialérgicos/farmacologia , Benzopiranos/química , Cálcio/metabolismo , Degranulação Celular/efeitos dos fármacos , Linhagem Celular , Flavanonas/isolamento & purificação , Glucuronatos/isolamento & purificação , Humanos , Sistema de Sinalização das MAP Quinases , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Proteínas Tirosina Quinases/metabolismo , Receptores de IgE/metabolismoRESUMO
Lycopodium clavatum has been used in traditional medicine for the treatment of kidney disorders, rheumatic arthritis, cystitis, and gastritis. We isolated a new serratane triterpenoid (2), and five known triterpenoids (1, 3-6) from the ethyl acetate fraction of L. clavatum by bioactivity-guided fractionation based on their suppression of inflammatory cytokines. Two different cell lines, RAW 264.7 and HT-29 were used to determine the anti-inflammatory activity of the isolated compounds. Among them, compounds 1, 2, 4, and 5 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages. Compounds 1, 2, 4, and 5 reduced inducible nitric oxide (iNOS) expression in RAW 264.7 cells and compounds 1 and 6 downregulated COX-2, which correlated with the reduced expression of PGE2. Compounds 1, 2, 4, and 5 downregulated pro-inflammatory cytokines, such as interleukin-1ß (IL-1ß) in macrophages, and additionally suppressed the levels of IL-8 in HT-29 cells. To determine the signaling pathways involved in the suppression of NO production by these compounds, we investigated ERK1/2 and nuclear factor-kappa B (NF-κB) expression by western blot analysis. We observed that these compounds downregulated the expression of LPS-induced NF-κB and pERK 1/2 in RAW 264.7 cells. Our results demonstrate that serratane triterpenoids isolated from L. clavatum may be used as potential candidates for treating inflammatory bowel disease (IBD) due to their anti-inflammatory effects.
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Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Mediadores da Inflamação/metabolismo , Lycopodium/química , Triterpenos/química , Triterpenos/farmacologia , Animais , Células HT29 , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Camundongos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Células RAW 264.7RESUMO
Alnus spp. (Betulaceae) have been used for treatments of hemorrhage, burn injuries, antipyretic fever, diarrhea, and alcoholism in traditional medicines. In this study, a digitized LC-MS/MS data analysis workflow was applied to provide an overview on chemical diversity of 15 Alnus extracts prepared from bark, twigs, leaves, and fruits of A. japonica, A. firma, A. hirsuta, and A. hirsuta var. sibirica. Most of the MS/MS spectra could be putatively annotated based on library matching, in silico fragmentation, and substructural topic modeling. The putative annotation allowed us to discriminate the extracts into three chemotypes based on dominant chemical scaffolds: diarylheptanoids, flavonoids or tannins. This high-throughput chemical annotation was correlated with α-glucosidase inhibition data of extracts, and it allowed us to identify gallic acid as the major active compound of A. firma.
Assuntos
Alnus , Diarileptanoides , Cromatografia Líquida , Análise de Dados , Extratos Vegetais , Espectrometria de Massas em Tandem , Fluxo de TrabalhoRESUMO
Citrus junos Tanaka is a traditional medicine for treating coughs, dyspepsia, diabetes, asthma, neuralgia, and inflammatory disorders, and is distributed in Asia, especially in Korea, Japan, and China. This study aimed to use bioactivity-guided fractionation to find therapeutic phytochemicals from C. junos seeds, which can attenuate inflammatory responses. Nine coumarins (1-9) were isolated from the methanolic extract of C. junos seed shells and the inhibitory effects against inflammatory mediators were investigated using murine macrophages. Among the coumarins, compound 3, isogosferol (ISO), more potently attenuated the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. ISO also inhibited the expression of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated macrophages. Additionally, the phosphorylation of extracellular-regulated kinases (pERK)1/2 was reduced by ISO. We confirmed that ISO attenuated the release of interleukin-1 beta (IL-1ß), which is a central mediator of the inflammatory response. These results demonstrate that ISO from C. junos seed shells may be a potent therapeutic candidate for the treatment of inflammatory diseases.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Citrus/química , Furocumarinas/isolamento & purificação , Furocumarinas/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Sementes/química , Animais , Anti-Inflamatórios/química , Sobrevivência Celular/efeitos dos fármacos , Fracionamento Químico , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Furocumarinas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Óleos de Plantas , Células RAW 264.7RESUMO
Nandina domestica (Berberidaceae) has been used in traditional medicine for the treatment of cough. This plant is distributed in Korea, Japan, China, and India This study aimed to investigate the anti-inflammatory phytochemicals obtained from the N. domestica fruits. We isolated a biflavonoid-type phytochemical, robustaflavone (R), from N. domestica fruits through bioactivity-guided fractionation based on its capacity to inhibit inflammation. The anti-inflammatory mechanism of R isolated from N. domestica has not yet been studied. In the present study, we evaluated the anti-inflammatory activities of R using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We have shown that R reduces the production of nitric oxide (NO), pro-inflammatory cytokine interleukin-1 beta (IL-1ß), and IL-6. Western blot analysis showed that R suppresses the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and downregulates the expression of LPS-induced nuclear factor-kappa B (NF-κB) and the phosphorylation of extracellular-regulated kinases (pERK 1/2). Moreover, R inhibited IL-8 release in LPS-induced human colonic epithelial cells (HT-29). These results suggest that R could be a potential therapeutic candidate for inflammatory bowel disease (IBD).
Assuntos
Berberidaceae/química , Biflavonoides/isolamento & purificação , Biflavonoides/farmacologia , Regulação para Baixo , Mediadores da Inflamação/metabolismo , Animais , Biflavonoides/química , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fracionamento Químico , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Enterócitos/efeitos dos fármacos , Enterócitos/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células HT29 , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/biossíntese , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Células RAW 264.7RESUMO
BACKGROUND: The goal of the study was to investigate the current clinical practices among oncologic surgeons regarding cytoreductive surgery (CRS) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: From September to October 2016, an online questionnaire surveyed the oncologic surgeons by email. The questionnaire included 20 multiple-choice questions of the following: eligibility for the CRS with HIPEC procedure, perioperative staging and surgery skill, assessment of residual tumors, and method used for intraperitoneal HIPEC. RESULTS: The response rate was 16% (34/217). The majority of respondents (68%) worked at a university hospital. All respondents indicated that mesenteric invasion is the most crucial factor affecting treatment decision. Most surgeons (79%) used the Sugarbaker's staging system to intraoperatively measure the extent of peritoneal invasion. The methods used to measure the extent of miliary pattern of residual tumor spread, and the amount of residual tumor after electrocauterization varied among the surgeons. Most responders (65%) used the closed system of HIPEC. CONCLUSIONS: Despite the fact that CRS HIPEC is the standard treatment for PSM, the clinical practices are very different according to each clinical situation. Nevertheless, mesenteric invasion was found to be the most important factor impacting the treatment decision-making by the majority of responders.
Assuntos
Quimioterapia do Câncer por Perfusão Regional/métodos , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Neoplasias Peritoneais/terapia , Padrões de Prática Médica , Inquéritos e Questionários , Adulto , Feminino , Humanos , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Prognóstico , Cirurgiões/estatística & dados numéricos , Taxa de SobrevidaRESUMO
Morus bombycis Koidzumi, commonly known as silkworm mulberry, is a plant belonging to family Moraceae. It has been used in Asian countries as a traditional medicine for treating hypertension, diabetes, and inflammatory disorders. In this study, we isolated eleven compounds from the cortex of M. bombycis and evaluated their inhibitory effects on nitric oxide (NO) production as an indicator of their anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated murine macrophages. Compound 4 showed the most potent inhibitory activity on NO production. It was identified as mulberrofuran K (MFK). Anti-inflammatory activity of MFK was then carried out using LPS-stimulated RAW264.7 cells. MFK suppressed the production of NO, reactive oxygen species (ROS), and proinflammatory cytokines (interleukin (IL)-1ß, IL-6 and tumor necrosis factor alpha (TNF-α)) in a concentration-dependent manner. Western blot analysis revealed that MFK treatment inhibited expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). MFK also inhibited transcriptional activation of nuclear factor-κB (NF-κB) and extracellular-regulated kinases (ERK) 1/2 in LPS-stimulated murine macrophages. These results suggest that MFK, an anti-inflammatory constituents of M. bombycis cortex, has potential as a therapeutic candidates for preventing and treating inflammatory diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Benzofuranos/farmacologia , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Medicina Tradicional do Leste Asiático , Animais , Citocinas/metabolismo , Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Camundongos , Morus/imunologia , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Casca de Planta , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismoRESUMO
Neural stem cells (NSCs) have the ability to proliferate and differentiate into neurons and glia. Regulation of NSC fate by small molecules is important for the generation of a certain type of cell. The identification of small molecules that can induce new neurons from NSCs could facilitate regenerative medicine and drug development for neurodegenerative diseases. In this study, we screened natural compounds to identify molecules that are effective on NSC cell fate determination. We found that Kuwanon V (KWV), which was isolated from the mulberry tree (Morus bombycis) root, increased neurogenesis in rat NSCs. In addition, during NSC differentiation, KWV increased cell survival and inhibited cell proliferation as shown by 5-bromo-2-deoxyuridine pulse experiments, Ki67 immunostaining and neurosphere forming assays. Interestingly, KWV enhanced neuronal differentiation and decreased NSC proliferation even in the presence of mitogens such as epidermal growth factor and fibroblast growth factor 2. KWV treatment of NSCs reduced the phosphorylation of extracellular signal-regulated kinase 1/2, increased mRNA expression levels of the cyclin-dependent kinase inhibitor p21, down-regulated Notch/Hairy expression levels and up-regulated microRNA miR-9, miR-29a and miR-181a. Taken together, our data suggest that KWV modulates NSC fate to induce neurogenesis, and it may be considered as a new drug candidate that can regenerate or protect neurons in neurodegenerative diseases.
Assuntos
Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Flavonoides/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Bromodesoxiuridina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Regulação para Baixo/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , MicroRNAs/genética , Morus/química , Fosforilação/efeitos dos fármacos , Raízes de Plantas/química , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
STUDY OBJECTIVE: Sleep spindles in humans have been classified as slow anterior and fast posterior spindles; recent findings indicate that their profiles differ according to pharmacology, pathology, and function. However, little is known about the generation mechanisms within the thalamocortical system for different types of spindles. In this study, we aim to investigate the electrophysiological behaviors of the topographically distinctive spindles within the thalamocortical system by applying high-density EEG and simultaneous thalamic LFP recordings in mice. DESIGN: 32-channel extracranial EEG and 2-channel thalamic LFP were recorded simultaneously in freely behaving mice to acquire spindles during spontaneous sleep. SUBJECTS: Hybrid F1 male mice of C57BL/6J and 129S4/svJae. MEASUREMENTS AND RESULTS: Spindle events in each channel were detected by spindle detection algorithm, and then a cluster analysis was applied to classify the topographically distinctive spindles. All sleep spindles were successfully classified into 3 groups: anterior, posterior, and global spindles. Each spindle type showed distinct thalamocortical activity patterns regarding the extent of similarity, phase synchrony, and time lags between cortical and thalamic areas during spindle oscillation. We also found that sleep slow waves were likely to associate with all types of sleep spindles, but also that the ongoing cortical decruitment/ recruitment dynamics before the onset of spindles and their relationship with spindle generation were also variable, depending on the spindle types. CONCLUSION: Topographically specific sleep spindles show distinctive thalamocortical network behaviors.
Assuntos
Sono/fisiologia , Algoritmos , Animais , Córtex Cerebral/fisiologia , Análise por Conglomerados , Eletroencefalografia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tálamo/fisiologiaRESUMO
The extract of Siegesbeckia pubescens herb and its chemical constituents were tested for the ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglia. The methanol extract and the 90% MeOH fraction of S. pubescens effectively attenuated lipopolysaccharide-induced nitric oxide production. Several steps of chromatography yielded eight ent-kaurane diterpenes (1-8) and one ent-pimarane diterpene (9) from the 90% MeOH fraction. Among these compounds, compounds 2-9 showed significant inhibitory effect on lipopolysaccharide-induced nitric oxide production in BV2 microglia. Compounds 3 and 9 concentration-dependently decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), supported by quantitative real time polymerase chain reaction (PCR) and Western blot analysis. These results suggest that ent-kaurane and ent-pimarane diterpenes isolated from S. pubescens are expected to be potential candidates against neuroinflammation-related disease.