RESUMO
Two Gram-positive, endospore-forming, rod-shaped bacterial strains designated MWE-103T and DLE-14T were isolated from plant roots. The 16S rRNA gene sequence analysis indicated that strain MWE-103T was closely related to Paenibaillus sacheonensis SY01T with a sequence similarity of 97.82â%, and strain DLE-14T to Paenibacillus rhizoryzae IZS3-5T with 99.09â% similarity. The orthologous average nucleotide identity and digital DNA-DNA hybridization values using whole genome data indicated that strains MWE-103T and DLE-14T could be readily distinguished from the mostly related species. Both strains grew at mesophilic temperature ranges, and grew best at pH 6 and in the absence of NaCl. The major fatty acid in both strains was anteiso-C15â:â0, but their relative proportions differed. The predominant quinone of both strains was menaquinone 7, the cell-wall diamino acid was meso-diaminopimelic acid, and the diagnostic polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol, which were consistent with those of related species. Amylase and cellulase activities were positive for both strains. Strain DLE-14T exhibited the potential for lignin degradation. The DNA G+C contents of strain MWE-103T and DLE-14T were 60.9 and 50.8 mol% respectively. The genomes of the two strains revealed potential plant-growth-promoting characteristics such as nitrogen fixation, siderophore production and phosphate solubilization. Based on phylogenetic and phenotypic evidence, strains MWE-103T and DLE-14T should each be recognized as a novel species of Paenibacillus, for which the names Paenibacillus artemisiicola sp. nov. (type strain: MWE-103T=KCTC 43287T=JCM 34503T) and Paenibacillus lignilyticus sp. nov. (type strain: DLE-14T=KCTC 43288T=JCM 34504T) are proposed.
Assuntos
Paenibacillus , Peptidoglicano , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Peptidoglicano/química , Fosfolipídeos/química , Filogenia , Raízes de Plantas/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Species are frequently responding to contemporary climate change by shifting to higher elevations and poleward to track suitable climate space. However, depending on local conditions and species' sensitivity, the nature of these shifts can be highly variable and difficult to predict. Here, we examine how the American pika (Ochotona princeps), a philopatric, montane lagomorph, responds to climatic gradients at three spatial scales. Using mixed-effects modeling in an information-theoretic approach, we evaluated a priori model suites regarding predictors of site occupancy, relative abundance, and elevational-range retraction across 760 talus patches, nested within 64 watersheds across the Northern Rocky Mountains of North America, during 2017-2020. The top environmental predictors differed across these response metrics. Warmer temperatures in summer and winter were associated with lower occupancy, lower relative abundances, and greater elevational retraction across watersheds. Occupancy was also strongly influenced by habitat patch size, but only when combined with climate metrics such as actual evapotranspiration. Using a second analytical approach, acute heat stress and summer precipitation best explained retraction residuals (i.e., the relative extent of retraction given the original elevational range of occupancy). Despite the study domain occurring near the species' geographic-range center, where populations might have higher abundances and be at lower risk of climate-related stress, 33.9% of patches showed evidence of recent extirpations. Pika-extirpated sites averaged 1.44â warmer in summer than did occupied sites. Additionally, the minimum elevation of pika occupancy has retracted upslope in 69% of watersheds (mean: 281 m). Our results emphasize the nuance associated with evaluating species' range dynamics in response to climate gradients, variability, and temperature exceedances, especially in regions where species occupy gradients of conditions that may constitute multiple range edges. Furthermore, this study highlights the importance of evaluating diverse drivers across response metrics to improve the predictive accuracy of widely used, correlative models.
Assuntos
Mudança Climática , Lagomorpha , Animais , Ecossistema , Estações do Ano , TemperaturaRESUMO
INTRODUCTION: Korean mugwort has been used as a traditional medicine. Specifically, air-dried Artemisia princeps Pamp. cv. ssajuari (ssajuari-ssuk; Korean mugwort) has been used as moxa in moxibustion therapy. Thus, the evaluation of high quality ssajuari-ssuk containing herbal volatiles is of great interest in clinical therapy and the food industry. OBJECTIVE: The aim of this study is to determine whether fast gas chromatography with uncoated surface acoustic wave (fast GC/SAW) sensor can be a useful technique for performing quality control using herbal volatiles of ssajuari-ssuk air-dried for different times. METHODOLOGY: Fast GC/SAW sensor, called "Electronic zNose", is also a headspace sampling method and is an effective simple analytical method with a second unit analysis providing on-line measurements without the need for pretreatment of the sample. Headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) was employed to confirm the identification of the volatiles and compared to fast GC/SAW sensor. RESULTS: Artemisia princeps Pamp. cv. ssajuari air-dried for 2 years and 4 months (the third year), containing the highest total amount of herbal volatiles, was superior to the others (the first year, the second year, the fourth year) in quality. Moreover, fast GC/SAW sensor shows a high repeatability (relative standard deviation 0.77% â¼ 6.23%), excellent sensitivity (limit of detection value of 0.47 pg/mL), and good linearity (correlation coefficient r2 = 0.997) over the range of nanogram for α-thujone. CONCLUSION: Therefore, the fast GC/SAW sensor can be a useful analytical method for the discrimination and quality control of volatiles of herbal and medicinal plants according to air-drying time, as it provides a simple and second unit analysis.
Assuntos
Artemisia , Compostos Orgânicos Voláteis , Humanos , Eletrônica , Cromatografia Gasosa-Espectrometria de Massas , Controle de Qualidade , República da Coreia , Microextração em Fase Sólida , Som , Compostos Orgânicos Voláteis/análiseRESUMO
The concept of biosimilar medicine was launched by 2001 and 2004 European Directives. First European marketing authorizations were delivered in 2006. They are "copies" of biologically manufactured medicines, mostly proteins. Taking into account the intrinsic variability related to the biological manufacture process, some variation of the chemical structure of the finished compound may be observed. They impact especially the glycosylation residues but not the amino-acid sequence (for proteins). For this reason, the marketing authorization application dossier has to involve, as opposed to the generic medicine procedure, the demonstration of the therapeutic equivalence in at least one clinical indication of the princeps medicine. Introduction of biosimilar medicines of monoclonal antibodies has represented a remarkable event in the domain of rheumatology, gastroenterology and dermatology with infliximab, etanercept and adalimumab biosimilars and in cancerology domains with rituximab, trastuzumab and bevacizumab biosimilars. Biosimilar medicines availability reduces the risk of drug supply rupture of princeps but their main impact is the economic one allowing cost reduction of costly princeps biological medicines. With the acquired clinical experience, the initial fears concerning switch form princeps to a biosimilar for a given patient has progressively disappeared.
RESUMO
Listeria innocua DNA binding protein from starved cells (LiDps) belongs to the ferritin family and provides a promising self-assembling spherical 12-mer protein scaffold for the generation of functional nanomaterials. We report the creation of a Gaussia princeps luciferase (Gluc)-LiDps fusion protein, with chemical conjugation of Zinc (II)-protoporphyrin IX (ZnPP) to lysine residues on the fusion protein (giving Gluc-LiDps-ZnPP). The Gluc-LiDps-ZnPP conjugate is shown to generate reactive oxygen species (ROS) via Bioluminescence Resonance Energy Transfer (BRET) between the Gluc (470-490â¯nm) and ZnPP. In vitro, Gluc-LiDps-ZnPP is efficiently taken up by tumorigenic cells (SKBR3 and MDA-MB-231 breast cancer cells). In the presence of coelenterazine, this construct inhibits the proliferation of SKBR3 due to elevated ROS levels. Following exposure to Gluc-LiDps-ZnPP, migration of surviving SKBR3 cells is significantly suppressed. These results demonstrate the potential of the Gluc-LiDps-ZnPP conjugate as a platform for future development of an anticancer photodynamic therapy agent.
Assuntos
Copépodes/enzimologia , Listeria/metabolismo , Luciferases/metabolismo , Medições Luminescentes , Nanopartículas/química , Fotoquimioterapia , Protoporfirinas/uso terapêutico , Animais , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/metabolismo , Humanos , Protoporfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
Many wildlife populations are either naturally, or as a result of human land use, patchily distributed in space. The degree of fragmentation-specifically the remaining patch sizes and habitat configuration-is an important part of population dynamics. Demographic stochasticity is also likely to play an important role in patchy habitats that host small local populations. We develop a simulation model to evaluate the significance of demographic stochasticity and the role fragmentation plays in the determination of population dynamics and the risk of extinction of populations on habitat patches. Our model is formulated as a Markov-chain stochastic process on a finite, spatially explicit array of patches in which probability of successful dispersal is a function of interpatch distance. Unlike past work, we explicitly model local population dynamics and examine how these scale up to the entire population. As a test case, we apply the model to the American pika (Ochotona princeps) population living on the ore dumps in the ghost mining town of Bodie, California. This population has been studied nearly continuously for over four decades and has been of conservation concern as the southern half of the population declined precipitously beginning in 1989. Our model suggests that both the specific configuration of habitat and landscape heterogeneity are necessary and sufficient predictors of the eventual extinction of the southern constellation of patches. This example has important implications, as it suggests that fragmentation alone can lead to regional extinctions within metapopulations.
Assuntos
Ecossistema , California , Demografia , Dinâmica Populacional , Processos EstocásticosRESUMO
Considerable attention has been paid to protein tyrosine phosphatase 1B (PTP1B) inhibitors as a potential therapy for diabetes, obesity, and cancer. Ten caffeoylquinic acid derivatives (1-10) from leaves of Artemisia princeps Pamp. (Asteraceae) were identified as natural PTP1B inhibitors. Among them, chlorogenic acid (3) showed the most potent inhibitory activity (IC50 11.1⯵M). Compound 3 was demonstrated to be a noncompetitive inhibitor by a kinetic analysis. Molecular docking simulation suggested that compound 3 bound to the allosteric site of PTP1B. Furthermore, compound 3 showed remarkable selectivity against four homologous PTPs. According to these findings, compound 3 might be potentially valuable for further drug development.
Assuntos
Artemisia/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Ácido Quínico/análogos & derivados , Relação Dose-Resposta a Droga , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Ácido Quínico/síntese química , Ácido Quínico/química , Ácido Quínico/farmacologia , Relação Estrutura-AtividadeRESUMO
Contemporary climate change affects nearly all biomes, causing shifts in animal distributions and resource availability. Changes in resource selection may allow individuals to offset climatic stress, thereby providing a mechanism for persistence amidst warming conditions. Whereas the role of predation risk in food choice has been studied broadly, the extent to which individuals respond to thermoregulatory risk by changing resource preferences is unclear. We addressed whether individuals compensated for temperature-related reductions in foraging time by altering forage preferences, using the American pika (Ochotona princeps) as a model species. We tested two hypotheses: (1) food-quality hypothesis-individuals exposed to temperature extremes should select higher-quality vegetation in return for accepting a physiologically riskier feeding situation; and (2) food-availability hypothesis-individuals exposed to temperature extremes should prioritize foraging quickly, thereby decreasing selection for higher-quality food. We quantified the composition and quality (% moisture, % nitrogen, and fiber content) of available and harvested vegetation, and deployed a network of temperature sensors to measure in situ conditions for 30 individuals, during July-Sept., 2015. Individuals exposed to more extreme daytime temperatures showed increased selection for high-nitrogen and for low-fiber vegetation, demonstrating strong support for the food-quality hypothesis. By contrast, pikas that experienced warmer conditions did not reduce selection for any of the three vegetation-quality metrics, as predicted by the food-availability hypothesis. By shifting resource-selection patterns, temperature-limited animals may be able to proximately buffer some of the negative effects associated with rapidly warming environments, provided that sufficient resources remain on the landscape.
Assuntos
Mudança Climática , Lagomorpha , Distribuição Animal , Animais , Ecossistema , TemperaturaRESUMO
Fresh collections, type studies and molecular phylogenetic analyses of a multigene matrix of partial nuSSU-ITS-LSU rDNA, rpb2, tef1 and tub2 sequences were used to evaluate the boundaries of Cucurbitaria in a strict sense and of several related genera of the Cucurbitariaceae. Two species are recognised in Cucurbitaria and 19 in Neocucurbitaria. The monotypic genera Astragalicola, Cucitella, Parafenestella, Protofenestella, and Seltsamia are described as new. Fenestella is here included as its generic type F. fenestrata (= F. princeps), which is lecto- and epitypified. Fenestella mackenzei and F. ostryae are combined in Parafenestella. Asexual morphs of Cucurbitariaceae, where known, are all pyrenochaeta- or phoma-like. Comparison of the phylogenetic analyses of the ITS-LSU and combined matrices demonstrate that at least rpb2 sequences should be added whenever possible to improve phylogenetic resolution of the tree backbone; in addition, the tef1 introns should be added as well to improve delimitation of closely related species.
RESUMO
How climate constrains species' distributions through time and space is an important question in the context of conservation planning for climate change. Despite increasing awareness of the need to incorporate mechanism into species distribution models (SDMs), mechanistic modeling of endotherm distributions remains limited in this literature. Using the American pika (Ochotona princeps) as an example, we present a framework whereby mechanism can be incorporated into endotherm SDMs. Pika distribution has repeatedly been found to be constrained by warm temperatures, so we used Niche Mapper, a mechanistic heat-balance model, to convert macroclimate data to pika-specific surface activity time in summer across the western United States. We then explored the difference between using a macroclimate predictor (summer temperature) and using a mechanistic predictor (predicted surface activity time) in SDMs. Both approaches accurately predicted pika presences in current and past climate regimes. However, the activity models predicted 8-19% less habitat loss in response to annual temperature increases of ~3-5 °C predicted in the region by 2070, suggesting that pikas may be able to buffer some climate change effects through behavioral thermoregulation that can be captured by mechanistic modeling. Incorporating mechanism added value to the modeling by providing increased confidence in areas where different modeling approaches agreed and providing a range of outcomes in areas of disagreement. It also provided a more proximate variable relating animal distribution to climate, allowing investigations into how unique habitat characteristics and intraspecific phenotypic variation may allow pikas to exist in areas outside those predicted by generic SDMs. Only a small number of easily obtainable data are required to parameterize this mechanistic model for any endotherm, and its use can improve SDM predictions by explicitly modeling a widely applicable direct physiological effect: climate-imposed restrictions on activity. This more complete understanding is necessary to inform climate adaptation actions, management strategies, and conservation plans.
Assuntos
Mudança Climática , Lagomorpha , Animais , Clima , Conservação dos Recursos Naturais , Ecossistema , Previsões , Dinâmica Populacional , Estados UnidosRESUMO
We offer a complete systemic review of the anatomy of arteries of the thumb, including their sources in the first web space. Eleven studies were selected from the PubMed, Medline, Embase, Scopus and Ovid databases. Data about each artery of the thumb were obtained; in particular, the incidence and dominance of each of these arteries were calculated. The ulnopalmar digital artery of the thumb (UPDAT) was found in 99.63%, the radiopalmar digital artery of the thumb (RPDAT) in 99.26%, the ulnodorsal digital artery of the thumb (UDDAT) in 83.39%, and the radiodorsal digital artery of the thumb (RDDAT) in 70.38%. The sources for the thumb arteries are the first palmar metacarpal artery (for UPDAT in 63.15%, for RPDAT in 78.88%, for UDDAT in 56.95% and for RDDAT in 41.48%), the first dorsal metacarpal artery (for UPDAT in 20.54%, for RPDAT 2.53%, for UDDAT in 20.62%, and for RDDAT in 4.81%) and the superficial palmar arch, either complete or incomplete (for UPDAT in 25.57%, for RPDAT in 23.04%, for UDDAT in 0%, and for RDDAT in 5.19%). The dominant source could be identified in 88.2% of cases: the first palmar metacarpal artery (66.2%), the first dorsal metacarpal artery (15.5%) and the superficial palmar arch, complete or incomplete (8.2%). Four arteries usually supply the thumb. Any artery in the first web space can be a source for the thumb arteries. We propose a new classification of the arteries of the hand, dividing them into three systems (superficial palmar, deep palmar and dorsal system), and suggest that the term "princeps pollicis artery" be reconsidered and systemic anatomical terms of the thumb arteries preferred. Clin. Anat. 30:963-973, 2017. ©2017 Wiley-Liss, Inc.
Assuntos
Artérias/anatomia & histologia , Polegar/irrigação sanguínea , Mãos/irrigação sanguínea , HumanosRESUMO
The Japanese mugwort, Artemisia princeps (yomogi in Japanese), has anti-inflammatory and antioxidant effects. Skin care products containing Artemisia princeps extract (APE) are known to improve dry skin symptoms in atopic dermatitis. Atopic dry skin is associated with a marked reduction of skin barrier proteins, such as filaggrin (FLG) and loricrin (LOR). Recently, aryl hydrocarbon receptor (AHR), and its downstream transcription factor OVO-like 1 (OVOL1), have been shown to regulate the gene expression of FLG and LOR. The focus of this paper is to evaluate the effects of APE on the AHR/OVOL1/FLG or LOR pathway since they have remained unknown to this point. We first demonstrated that non-cytotoxic concentrations of APE significantly upregulated antioxidant enzymes, NAD(P)H dehydrogenase quinone 1 and heme oxygenase 1, in human keratinocytes. Even at these low concentrations, APE induced nuclear translocation of AHR and significantly upregulated CYP1A1 (a specific target gene for AHR activation), FLG, and LOR expression. AHR knockdown downregulated OVOL1 expression. The APE-induced upregulation of FLG and LOR was canceled in keratinocytes with AHR or OVOL1 knockdown. In conclusion, antioxidant APE is a potent phytoextract that upregulates FLG and LOR expression in an AHR/OVOL1-dependent manner and this may underpin the barrier-repairing effects of APE in treating atopic dry skin.
Assuntos
Antioxidantes/farmacologia , Artemisia/química , Proteínas de Filamentos Intermediários/metabolismo , Proteínas de Membrana/metabolismo , Extratos Vegetais/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas Filagrinas , Humanos , Proteínas de Filamentos Intermediários/genética , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Proteínas de Membrana/genética , NADPH Desidrogenase/genética , NADPH Desidrogenase/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Ecological niche theory holds that species distributions are shaped by a large and complex suite of interacting factors. Species distribution models (SDMs) are increasingly used to describe species' niches and predict the effects of future environmental change, including climate change. Currently, SDMs often fail to capture the complexity of species' niches, resulting in predictions that are generally limited to climate-occupancy interactions. Here, we explore the potential impact of climate change on the American pika using a replicated place-based approach that incorporates climate, gene flow, habitat configuration, and microhabitat complexity into SDMs. Using contemporary presence-absence data from occupancy surveys, genetic data to infer connectivity between habitat patches, and 21 environmental niche variables, we built separate SDMs for pika populations inhabiting eight US National Park Service units representing the habitat and climatic breadth of the species across the western United States. We then predicted occurrence probability under current (1981-2010) and three future time periods (out to 2100). Occurrence probabilities and the relative importance of predictor variables varied widely among study areas, revealing important local-scale differences in the realized niche of the American pika. This variation resulted in diverse and - in some cases - highly divergent future potential occupancy patterns for pikas, ranging from complete extirpation in some study areas to stable occupancy patterns in others. Habitat composition and connectivity, which are rarely incorporated in SDM projections, were influential in predicting pika occupancy in all study areas and frequently outranked climate variables. Our findings illustrate the importance of a place-based approach to species distribution modeling that includes fine-scale factors when assessing current and future climate impacts on species' distributions, especially when predictions are intended to manage and conserve species of concern within individual protected areas.
Assuntos
Mudança Climática , Ecossistema , Lagomorpha , Modelos Teóricos , Animais , Fluxo Gênico , Lagomorpha/genética , Dinâmica Populacional , Estações do Ano , Estados Unidos , Tempo (Meteorologia)RESUMO
Landscape connectivity is essential for maintaining viable populations, particularly for species restricted to fragmented habitats or naturally arrayed in metapopulations and facing rapid climate change. The importance of assessing both structural connectivity (physical distribution of favorable habitat patches) and functional connectivity (how species move among habitat patches) for managing such species is well understood. However, the degree to which functional connectivity for a species varies among landscapes, and the resulting implications for conservation, have rarely been assessed. We used a landscape genetics approach to evaluate resistance to gene flow and, thus, to determine how landscape and climate-related variables influence gene flow for American pikas (Ochotona princeps) in eight federally managed sites in the western United States. We used empirically derived, individual-based landscape resistance models in conjunction with predictive occupancy models to generate patch-based network models describing functional landscape connectivity. Metareplication across landscapes enabled identification of limiting factors for dispersal that would not otherwise have been apparent. Despite the cool microclimates characteristic of pika habitat, south-facing aspects consistently represented higher resistance to movement, supporting the previous hypothesis that exposure to relatively high temperatures may limit dispersal in American pikas. We found that other barriers to dispersal included areas with a high degree of topographic relief, such as cliffs and ravines, as well as streams and distances greater than 1-4 km depending on the site. Using the empirically derived network models of habitat patch connectivity, we identified habitat patches that were likely disproportionately important for maintaining functional connectivity, areas in which habitat appeared fragmented, and locations that could be targeted for management actions to improve functional connectivity. We concluded that climate change, besides influencing patch occupancy as predicted by other studies, may alter landscape resistance for pikas, thereby influencing functional connectivity through multiple pathways simultaneously. Spatial autocorrelation among genotypes varied across study sites and was largest where habitat was most dispersed, suggesting that dispersal distances increased with habitat fragmentation, up to a point. This study demonstrates how landscape features linked to climate can affect functional connectivity for species with naturally fragmented distributions, and reinforces the importance of replicating studies across landscapes.
Assuntos
Ecossistema , Lagomorpha/genética , Modelos Genéticos , Distribuição Animal , Animais , Clima , DNA/genética , Fluxo Gênico , Estados UnidosRESUMO
Five undescribed eudesmane methyl esters (1-5), three undescribed eudesmane-12,6-olides (6-8), and 21 known analogues (9-29) were isolated from the aerial part of Artemisia princeps Pamp. Their structures were established by detailed analysis of the NMR and HRESIMS data. The absolute configurations of 1-8 were determined based on single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory effects on LPS-induced NO production in BV-2 microglial cells of all the isolated compounds were assessed. Except for compounds 2, 4, 10, and 11, the others showed significant inhibitory activities, with IC50 values of 0.73-18.66 µM, wherein the potential structure-activity relationship was also discussed.
Assuntos
Artemisia , Sesquiterpenos de Eudesmano , Sesquiterpenos , Artemisia/química , Estrutura Molecular , Sesquiterpenos/química , Relação Estrutura-Atividade , Sesquiterpenos de Eudesmano/farmacologia , Sesquiterpenos de Eudesmano/químicaRESUMO
Protein-fragment complementation assays (PCAs) are powerful tools to investigate protein-protein interactions in a cellular context. These are especially useful to study unstable proteins and weak interactions that may not resist protein isolation or purification. The PCA based on the reconstitution of the Gaussia princeps luciferase (split-luc) is a sensitive approach allowing the mapping of protein-protein interactions and the semiquantitative measurement of binding affinity. Here, we describe the split-luc protocol we used to map the viral interactome of measles virus polymerase complex.
Assuntos
Vírus do Sarampo , Ligação Proteica , Mapeamento de Interação de Proteínas , Mapeamento de Interação de Proteínas/métodos , Humanos , Luciferases/metabolismo , Luciferases/genética , Proteínas Virais/metabolismo , RNA Polimerase Dependente de RNA/metabolismoRESUMO
OBJECTIVE: The aim of the present study was to investigate antioxidant and the anticancerigen activity of a methanol extract from Artemisia princeps var. orientalis (APME), a well-known traditional herbal medicine in Asia, in hepatocellular cancer cells. METHODS: To evaluate the antioxidant activity of APME, reactive oxygen species (ROS) and the antioxidant enzymes, superoxide dismutase (SOD) and catalase were investigated in HepG2 cells exposed to APME (5, 100, and 200 µg/mL) for 72 h. Then, to evaluate the anticancer activity of APME, we investigated the proliferation and apoptosis induction of HepG2 and Hep3B cells exposed to APME (1-200 µg/mL) for 24, 48, and 72 h. RESULTS: APME dose-dependently reduced the generation of ROS in the presence of H2O2 compared with control cells. Furthermore, it increased catalase and SOD activity. Moreover, APME inhibited cell proliferation in a dose- and time-dependent manner, but at concentrations lower than 100 µg/mL, the inhibition was less dose-dependent than time-dependent. HepG2 and Hep3B cells exposed to 5, 100, and 200 µg/mL APME for 72 h underwent cell cycle arrest and apoptosis. Exposure to APME resulted in a significant increase in the number of cells in G1 phase and a decrease in the G2/M phase cell population. In addition, APME induced P53 expression of HepG2 cells in a dose-dependent manner, and played a role in the downregulation of Bcl-2 and upregulation of Bax in both HepG2 and Hep3B cells. CONCLUSIONS: These results indicate the potential role of APME as an antioxidant and anticancerigen agent in hepatocarcinoma cell lines.
RESUMO
Bioassay-guided investigation of the active fraction of Artemisia princeps led to 13 undescribed sesquiterpenoid dimers, artemiprinolides A-M (1-13), together with 11 known ones (14-24). Their structures were elucidated by comprehensive spectroscopic data and absolute configurations were assigned based on single crystal X-ray diffraction data and ECD calculations. Structurally, all compounds were postulated to be derived from the Diels-Alder cycloaddition. The isolated dimers except 11 and 15 were assayed for their cytotoxicity against HepG2, Huh7, and SK-Hep-1 cell lines, of which four compounds (3, 13, 17, 18) exhibited obvious cytotoxicity with IC50 values ranging from 8.8 to 20.1 µM. Interestingly, the most active compounds 1 and 16 manifested significant cytotoxicity on the three tested hepatoma cell lines with IC50 values of 5.4, 4.1 (HepG2), 7.7, 5.6 (Huh7), and 11.8, 15.7 µM (SK-Hep-1), respectively, which were better than sorafenib. Compound 1 dose-dependently inhibited cell migration and invasion, and significantly induced the HepG2 cell arrest in G2/M phase by downregulating cdc2 and pcdc2 and upregulating cyclinB1; and induced apoptosis by downregulating Bcl-2 expression and upregulating Bax level. The molecular docking study implied that the carbonyl at the C-12' of 1 had a strong binding affinity with PRKACA.
Assuntos
Artemisia , Carcinoma Hepatocelular , Sesquiterpenos , Artemisia/química , Simulação de Acoplamento Molecular , Sesquiterpenos/química , Carcinoma Hepatocelular/tratamento farmacológico , Apoptose , Estrutura MolecularRESUMO
Four sesquiterpenoids were isolated from an ethyl acetate-soluble fraction of A. princeps ethanolic extract: seco-tanapartholide B (5-epi-seco-tanapartholide A) (1), 4-epi-seco-tanapartholide A (2), 11,13-dehydrodesacetylmatricarin (3) and desacetylmatricarin (4). Compounds 1 - 3 dose-dependently inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages. These compounds also decreased mRNA and protein expression levels of inducible NO synthase and cyclooxygenase-2 as well as mRNA levels of pro-inflammatory cytokines (interleukin-1ß and tumour necrosis factor-α) in LPS-stimulated RAW 264.7 macrophages. Moreover, compound 3 effectively enhanced the expression of heme oxygenase-1 (HO-1) in macrophages in the presence or absence of LPS. Additionally, the exocyclic methylene of α-methylene-γ-lactone moiety of compound 3 was found to be essential for the activation of the NF erythroid 2-related factor 2 (Nrf2)/HO-1 pathway. Here, we firstly report the isolation of compounds 3 and 4 from A. princeps and the anti-inflammatory activity of compound 3 by up-regulation of Nrf2/HO-1 pathway.
Assuntos
Artemisia , Sesquiterpenos , Animais , Camundongos , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Artemisia/metabolismo , Macrófagos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Sesquiterpenos/farmacologia , Sesquiterpenos/metabolismo , RNA Mensageiro/genética , Células RAW 264.7 , Óxido Nítrico/metabolismoRESUMO
BACKGROUND: Artemisia argyi Lévl. et Van., Artemisia princeps Pamp., and Artemisia montana Pamp., which are the sources of mugwort, have been popular across East Asian countries for nearly 2000 years now. Essential oils are the major chemical component obtained from them, exhibiting a variety of biological activities. OBJECTIVE: This review mainly focuses on the chemical composition and biological activities of A. argyi essential oil (AAEO), A. princeps essential oil (APEO), and A. montana essential oil (AMEO), with a special focus on their common and specific characteristics. The traditional use, distribution, and botany of A. argyi, A. princeps, and A. montana have also been summarized. In addition, the pharmacokinetics of AAEO was involved. METHODS: We collected literature from online and offline databases by entering the following keywords: mugwort, wormwood, A. argyi, A. princeps, A. montana, essential oil, and volatile oil. No language limitation was present in our search. RESULTS: A. argyi, A. princeps, and A. montana were used as traditional medicine, food, and health care products for a long time in Asia. They are widely distributed in most parts of China, Korea, and Japan. AAEO, APEO, and AMEO composed of monoterpenes, sesquiterpenes and their derivatives, alkanes, olefins, etc. Most of the specific compounds of AAEO were monoterpenoids, nearly half of the specific compounds of APEO were aliphatic hydrocarbons, and the sesquiterpenes were the typical specific compounds of AMEO. The mugwort essential oil showed multiple biological activities, such as anti-microbial, anti-inflammatory, antioxidant, antitumor, anticoagulation, sedative, and insecticide. CONCLUSION: The present review provided insight into the chemical composition and biological activity of AAEO, APEO, and AMEO. The comprehensive literature showed that they possessed wide application prospects in various fields. However, they should be studied in more depth. The underlying bioactive mechanisms should be elucidated and their toxicity and quality control should be determined.