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Trichospira verticillata is an annual herb that belongs to the family Asteraceae. Trichospira verticillata extract (TVE) elicits anti-plasmodial activity; however, there has been no detailed report about its anti-inflammatory effects and molecular mechanisms. In addition, herbal plants exhibit anti-inflammatory effects by suppressing the NLRP3 inflammasome. Therefore, the primary goal of this study was to examine the effects of TVE on NLRP3 inflammasome activation by measuring interleukin-1ß (IL-1ß) secretion. We treated lipopolysaccharides (LPS)-primed J774A.1 and THP-1 cells with TVE, which attenuated NLRP3 inflammasome activation. Notably, TVE did not affect nuclear factor-kappa B (NF-κB) signalling or intracellular reactive oxygen species (ROS) production and potassium efflux, suggesting that it inactivates the NLRP3 inflammasome via other mechanisms. Moreover, TVE suppressed the formation of apoptosis-associated speck-like protein (ASC) speck and oligomerization. Immunoprecipitation data revealed that TVE reduced the binding of NLRP3 to NIMA-related kinase 7 (NEK7), resulting in reduced ASC oligomerization and speck formation. Moreover, TVE alleviated neutrophilic asthma (NA) symptoms in mice. This study demonstrates that TVE modulates the binding of NLPR3 to NEK7, thereby reporting novel insights into the mechanism by which TVE inhibits NLRP3 inflammasome. These findings suggest TVE as a potential therapeutic of NLRP3 inflammasome-mediated diseases, particularly NA.
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Antiinflamatorios , Asma , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Neutrófilos , Especies Reactivas de Oxígeno , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Animales , Inflamasomas/metabolismo , Asma/metabolismo , Asma/tratamiento farmacológico , Asma/inmunología , Asma/patología , Ratones , Antiinflamatorios/farmacología , Humanos , Neutrófilos/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Especies Reactivas de Oxígeno/metabolismo , Lipopolisacáridos , Quinasas Relacionadas con NIMA/metabolismo , Interleucina-1beta/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Modelos Animales de Enfermedad , Extractos Vegetales/farmacología , Células THP-1RESUMEN
Root extracts of Ancistrocladus tectorius (AT), a shrub native to China, have been shown to have antiviral and antitumor activities, but the anti-obesity effects of AT aerial parts, mainly the leaves and stems, have not been investigated. This study is the first to investigate the anti-obesity effects and molecular mechanism of AT 70% ethanol extract in 3T3-L1 adipocytes and high-fat diet (HFD)-fed C57BL/6J mice. Treatment with AT extract inhibited lipid accumulation in 3T3-L1 cells and decreased the expression of adipogenesis-related genes. AT extract also upregulated the mRNA expression of genes related to mitochondrial dynamics in 3T3-L1 adipocytes. AT administration for 12 weeks reduced body weight and organ weights, including liver, pancreas, and white and brown adipose tissue, and improved plasma profiles such as glucose, insulin, homeostasis model assessment of insulin resistance, triglyceride (TG), and total cholesterol in HFD-fed mice. AT extract reduced HFD-induced hepatic steatosis with levels of liver TG and lipogenesis-related genes. AT extract upregulated thermogenesis-related genes such as Cidea, Pgc1α, Ucp1, Prdm16, Adrb1, and Adrb3 and mitochondrial dynamics-related genes such as Mff, Opa1, and Mfn2 in brown adipose tissue (BAT). Therefore, AT extract effectively reduced obesity by promoting thermogenesis and the mitochondrial dynamics of BAT in HFD-fed mice.
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Caryophyllales , Dieta Alta en Grasa , Animales , Ratones , Ratones Endogámicos C57BL , Dieta Alta en Grasa/efectos adversos , Dinámicas Mitocondriales , Insulina , Extractos Vegetales/farmacologíaRESUMEN
BACKGROUND: The infraspinatus muscle has a crucial role in shoulder stability. Although axial shoulder rotation is useful for selective activation of the infraspinatus, no study has examined the influence of exercise position on axial shoulder rotation during shoulder external rotation (ER) exercises. Thus, this study investigated the muscle activity in the infraspinatus, posterior deltoid, and middle trapezius during shoulder ER exercises performed with and without controlled axial shoulder rotation in 2 different positions. METHODS: Twenty healthy subjects performed prone external rotation (PER) exercises with and without pressure biofeedback and seated external rotation (SITER) exercises with and without posterior humeral head gliding. Muscle activity during each ER exercise was measured using surface electromyography. RESULTS: Exercise strategy (P < .001) and position (P < .001) had a significant main effect on muscle activity in the infraspinatus and posterior deltoid. However, no significant interaction between strategy and position was observed. For muscle activity in the middle trapezius, strategy and position had a significant interaction effect (P = .014). Muscle activity in the infraspinatus increased significantly with the use of strategies to control axial shoulder rotation, whereas muscle activity in the posterior deltoid and middle trapezius decreased significantly. For all 3 muscles, greater activity was observed in the prone position than the seated position. CONCLUSION: We suggest that PER with pressure biofeedback can be useful to improve selective activation of the infraspinatus muscle while further eliciting infraspinatus muscle activity.
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Articulación del Hombro , Hombro , Electromiografía , Humanos , Músculo Esquelético , Rotación , Manguito de los RotadoresRESUMEN
Caragana rosea Turcz, which belongs to the Leguminosae family, is a small shrub found in Northern and Eastern China that is known to possess anti-inflammatory properties and is used to treat fever, asthma, and cough. However, the underlying molecular mechanisms of its anti-inflammatory effects are unknown. Therefore, we used lipopolysaccharide (LPS) in RAW264.7 macrophages to investigate the molecular mechanisms that underlie the anti-inflammatory activities of a methanol extract of Caragana rosea (Cr-ME). We showed that Cr-ME reduced the production of nitric oxide (NO) and mRNA levels of iNOS, TNF-α, and IL-6 in a concentration-dependent manner. We also found that Cr-ME blocked MyD88- and TBK1-induced NF-κB and IRF3 promoter activity, suggesting that it affects multiple targets. Moreover, Cr-ME reduced the phosphorylation levels of IκBα, IKKα/ß and IRF3 in a time-dependent manner and regulated the upstream NF-κB proteins Syk and Src, and the IRF3 protein TBK1. Upon overexpression of Src and TBK1, Cr-ME stimulation attenuated the phosphorylation of the NF-κB subunits p50 and p65 and IRF3 signaling. Together, our results suggest that the anti-inflammatory activity of Cr-ME occurs by inhibiting the NF-κB and IRF3 signaling pathways.
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Antiinflamatorios/farmacología , Caragana/química , Inflamación/tratamiento farmacológico , Metanol/química , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Células Cultivadas , Células HEK293 , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Factor 3 Regulador del Interferón/antagonistas & inhibidores , Factor 3 Regulador del Interferón/metabolismo , Lipopolisacáridos/antagonistas & inhibidores , Ratones , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/antagonistas & inhibidores , Receptor Toll-Like 4/metabolismoRESUMEN
The potential biological activities of Viburnum stellato-tomentosum (VS), a plant mainly found in Costa Rica, have yet to be reported. Supplementation of VS extract for 17 weeks significantly decreased body weight gain, fat weight, fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride levels in high-fat diet (HFD)-fed C57BL/6J mice. The molecular mechanisms underlying the anti-obesity and glucose-lowering effects of VS extract were investigated. VS extract suppressed adipocyte hypertrophy by regulating lipogenesis-related CCAAT/enhancer-binding protein α (C/EBPα) and insulin sensitivity-related peroxisome proliferator-activated receptor γ (Pparg) expression in adipose tissue (AT) and hepatic steatosis by inhibiting C/EBPα and lipid transport-related fatty acid binding protein 4 (FABP4) expression. VS extract enhanced muscular fatty acid ß-oxidation-related AMP-activated protein kinase (AMPK) and PPARα expression with increasing Pparg levels. Furthermore, VS extract contained a much higher content of amentoflavone (AMF) (29.4 mg/g extract) compared to that in other Viburnum species. AMF administration decreased Cebpa and Fabp4 levels in the AT and liver, as well as improved insulin signaling-related insulin receptor substrate 1 (Irs1) and glucose transporter 1 (Glut1) levels in the muscle of HFD-fed mice. This study elucidated the in vivo molecular mechanisms of AMF for the first time. Therefore, VS extract effectively diminished obesity and hyperglycemia by suppressing C/EBPα-mediated lipogenesis in the AT and liver, enhancing PPARα-mediated fatty acid ß-oxidation in muscle, and PPARγ-mediated insulin sensitivity in AT and muscle.
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Fármacos Antiobesidad/uso terapéutico , Dieta Alta en Grasa , Hiperglucemia/tratamiento farmacológico , Metabolismo de los Lípidos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Extractos Vegetales/uso terapéutico , Viburnum/química , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos/patología , Adipogénesis/efectos de los fármacos , Tejido Adiposo Blanco/patología , Animales , Fármacos Antiobesidad/farmacología , Biflavonoides/farmacología , Peso Corporal/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Hígado Graso/sangre , Hígado Graso/complicaciones , Hígado Graso/tratamiento farmacológico , Conducta Alimentaria , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Homeostasis/efectos de los fármacos , Hiperglucemia/sangre , Hiperglucemia/complicaciones , Hiperglucemia/metabolismo , Hipertrofia , Insulina/metabolismo , Resistencia a la Insulina , Metabolismo de los Lípidos/efectos de los fármacos , Ratones Endogámicos C57BL , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Obesidad/sangre , Obesidad/complicaciones , Tamaño de los Órganos/efectos de los fármacos , Oxidación-Reducción , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
CONTEXT: Asymmetrical movements of trunk and lower-extremity are common during the bridge exercise on the unstable condition. However, no studies have investigated whether visual biofeedback of pressing pressure on the unstable surface changes muscle activation patterns of trunk and hip extensors and pelvic rotation during the bridge exercise. OBJECTIVE: To investigate how visual biofeedback of pressing pressure influences symmetrical activity of lumbar and hip extensor and pelvic rotation. DESIGN: Cross-sectional study. SETTING: Laboratory. PARTICIPANTS: Twenty healthy males participated in this study. INTERVENTIONS: The participants performed 2 versions of the bridge exercise: the standard bridge exercise and the bridge exercise with visual biofeedback using amount of pressing pressure on the sling. MAIN OUTCOME MEASURES: Surface electromyography was used to measure the symmetry (ie, the difference between dominant and nondominant sides) of muscle activation in the bilateral erector spinae, gluteus maximus, and hamstring muscles, and motion sensors were used to assess pelvic rotation. Symmetry of pressing pressure was measured using a tension meter. RESULTS: The differences between the dominant and nondominant pressing pressures and differences between the electromyography activity of the dominant and nondominant erector spinae, gluteus maximus, and hamstring were significantly smaller during the bridge exercise with visual biofeedback than during the standard bridge exercise (P < .05). In addition, there was significantly less pelvic rotation during the bridge exercise with visual biofeedback than during the standard bridge exercise (P < .05). CONCLUSIONS: The present findings suggest that visual biofeedback strategy may be a useful method for enhancing the symmetrical activation of the erector spinae, gluteus maximus, and hamstring and for reducing pelvic rotation during the bridge exercise on the unstable surface.
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Ejercicio Físico , Músculo Esquelético , Biorretroalimentación Psicológica , Estudios Transversales , Electromiografía , Humanos , Masculino , Músculos ParaespinalesRESUMEN
[Purpose] The purpose of this study was to determine the effects of non-paretic arm movement during the bridge exercise on trunk muscle activity in stroke patients. [Participants and Methods] In total, 18 stroke patients were recruited. Surface EMG electrodes were attached over the trunk muscles (rectus abdominis, RA; internal oblique, IO; erector spinae, ES), and three kinds of bridge exercises were performed: 1) 'standard' bridge, 2) bridge with unilateral isometric arm flexion, and 3) bridge with unilateral isometric arm horizontal abduction. [Results] According to the activity of the trunk muscles measured during bridge exercises, only the IO and ES showed significantly greater muscle activity during bridges with isometric arm horizontal abduction and flexion than during the standard bridge. Additionally, comparison of the paretic and non-paretic sides showed that muscle activity was higher on the paretic side. [Conclusion] This study showed that, as an exercise to heighten the activity of the trunk muscles in stroke patients, bridge exercises with accompanying non-paretic arm flexion and horizontal abduction were more effective clinically than a standard bridge.
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[Purpose] The purpose of this study was to investigate the effect of isometric hip adduction and abduction on trunk muscle activity during plank exercises. [Subjects and Methods] Nineteen healthy male subjects were recruited for this study. All subjects performed the traditional plank exercise (TP), plank exercise with isometric hip adduction (PHAD), and plank exercise with isometric hip abduction (PHAB) by using an elastic band. Electromyographic (EMG) activities of the internal oblique (IO) and external oblique (EO) were measured during the 3 plank exercises by using an Electromyography system. [Results] Internal oblique and external oblique muscle activities were significantly greater during plank exercise with isometric hip adduction and plank exercise with isometric hip abduction than during traditional plank exercise. Internal oblique and external oblique muscle activities did not differ between the plank exercise with isometric hip adduction and plank exercise with isometric hip abduction conditions. [Conclusion] These findings demonstrate that loaded isometric hip movements may be a useful strategy to increase trunk muscle activity during plank exercises.
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Guanine (G)-quadruplexes are of interest because of their presence in the telomere sequence and the oncogene promoter region. Their diffusion and change of structure, especially in high viscosity solutions, are important for understanding their dynamics. G-quadruplexes may have less effective viscosity (nanoviscosity) when they are smaller than the solvent molecules. In this paper, we report the difference in the diffusion dynamics of the G-rich DNA sequences of single-strand DNA (ssDNA) and the G-quadruplex in aqueous, sucrose, and polyethylene glycol (PEG) solutions. From experiments with aqueous and sucrose solutions, we confirm that a simple diffusion model according to the viscosity is appropriate. In the PEG experiments, the nanoviscosity effect is observed according to PEG's molecular weight. In the PEG 200 solution, both the ssDNA and the G-quadruplex possess macroviscosity. In the PEG 10,000 solution, the G-quadruplex possesses nanoviscosity and the ssDNA possesses macroviscosity, whereas, in the PEG 35,000 solution, both ssDNA and the G-quadruplex possess nanoviscosity. The experimental results are consistent with the theoretical predictions.
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ADN de Cadena Simple/química , G-Cuádruplex , Peso Molecular , Polietilenglicoles/química , Espectrometría de Fluorescencia , ViscosidadRESUMEN
[Purpose] This study investigated the effects of the Neurac technique on shoulder pain, function, and range of motion in patients with acute-phase subacromial impingement syndrome. [Subjects] Thirteen patients (seven females and six males) with acute-phase subacromial impingement syndrome participated in this study. [Methods] Shoulder pain, function, and range of motion were assessed before and after the application of the Neurac technique. [Results] Pain and function scores were significantly lower after than before the Neurac intervention. Shoulder range of motion was significantly greater after Neurac intervention than before it. [Conclusion] The Neurac technique is a useful intervention for patients with acute-phase subacromial impingement syndrome.
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[Purpose] The aim of this study was to investigate the effect of kinesio taping (KT) on the kinematics of the lumbo-pelvic-hip complex during forward bending by individuals with reduced hamstring extensibility. [Subjects] Eighteen males with reduced hamstring extensibility were randomly assigned to one of two groups:, the hamstring KT group (n=9), or the sham KT group (n=9). [Methods] The kinematics of the lumbopelvic-hip complex during lumbar forward bending was measured using a motion capture system before and after applying KT. [Results] The angle of lumbar flexion during late lumbar forward bending increased significantly post-KT compared to pre-KT measurements in the hamstring KT group. [Conclusion] These findings suggest that KT does not directly affect an individual's movement during lumbar forward bending.
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[Purpose] The purpose of this study was to investigate the effect of gastrocnemius stretching combined with talocrural joint mobilization on weight-bearing ankle dorsiflexion passive range of motion. [Subjects] Eleven male subjects with bilateral limited ankle dorsiflexion passive range of motion with knee extended participated in this study. [Methods] All subjects received talocrural joint mobilization while performing gastrocnemius stretching. Ankle dorsiflexion passive range of motion was measured using an inclinometer under weight-bearing conditions before and immediately after intervention. A paired t-test was used to analyze the difference between weight-bearing ankle dorsiflexion passive range of motion pre- and post-intervention. [Results] A significant increase in weight-bearing ankle dorsiflexion passive range of motion was found post-intervention compared with pre-intervention. [Conclusion] These findings demonstrate that gastrocnemius stretching combined with joint mobilization is effective for increasing weight-bearing ankle dorsiflexion passive range of motion.
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[Purpose] This study investigated the reliability of ankle dorsiflexion passive range of motion (DF-PROM) measurements obtained using a goniometer and Biodex dynamometer in stroke patients. [Subjects] Fifteen stroke patients participated in this study. [Methods] Ankle DF-PROM was assessed using a goniometer and Biodex dynamometer. Ankle DF-PROM was measured during two sessions with 7 days between tests. Intraclass correlation coefficient, standard error of measurement, and minimal detectable change values were used to assess the reliability of measurements obtained using both instruments. [Results] The intra-rater reliability for ankle DF-PROM using the goniometer was moderate and good for the two raters, while using the Biodex dynamometer, it was good for both raters. Inter-rater reliability using the goniometer was moderate; using the Biodex, it was good. [Conclusion] Both intra- and inter-reliability measurements of ankle DF-PROM were higher using a Biodex dynamometer than with a goniometer.
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To measure the polarization dependence of fluorescent probes, a confocal-microscope-based polarized fluorescence correlation spectroscopy system was developed, and the polarization dependence on the rotational diffusion of well-defined quantum rods (Qrods) was investigated and characterized. The rotational diffusion region of the Qrods was observed over a time range of less than 10(-5) s in a water solution, and the rotational diffusion parameters were extracted using a rotational diffusion model in which the viscosity of the solution media was varied. Our work demonstrated that polarized fluorescence correlation spectroscopy (FCS) is useful for investigating both the rotational and translational diffusion of fluorescent probes.
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Difusión , Colorantes Fluorescentes/química , Puntos Cuánticos , Espectrometría de FluorescenciaRESUMEN
BACKGROUND: An evaluation of scapula position is important to predict spine curvature and shoulder function in patients with adolescent idiopathic scoliosis (AIS). Therefore, a reliable scapula position is required to assess posture in patients with AIS. OBJECTIVE: This study investigated the reliabilities of scapula position tests and differences in scapula position and shoulder function between individuals with and without AIS. METHODS: The study compared 18 patients with AIS and 18 healthy controls to identify differences in scapula position and shoulder function. The acromion-table distance, lateral displacement of the scapula, acromion depression, winged scapula, upward rotation of the scapula, and anterior tilt of the scapula were measured. Scapula position test reliabilities were assessed using the intraclass correlation coefficient (ICC), standard error of measurement (SEM), and minimum clinically important difference (MCID). Shoulder function was measured using the Shoulder Pain and Disability Index. RESULTS: The reliabilities of scapula position tests (ICC 0.85-0.93, SEM 0.1-1.2, and MCID 0.2-2.5) were good. There were significant differences in scapula position and shoulder function between patients with AIS and healthy controls (p< 0.05). CONCLUSION: Scapula position tests were highly reliable in patients with AIS; they can be used to evaluate scapula position during clinical assessment of posture in patients with AIS.
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In this study, we report the complete plastome sequence of Cardamine glechomifolia H.Lév. 1913 (NCBI acc. no. OP894664). This plastome shows typical quadripartite structure. The plastome size is 154,307 bp, which consists of 84,015 bp large single-copy (LSC), 17,690 bp small single-copy (SSC), and 26,301 bp inverted repeat (IR) regions. The plastome contains 112 genes, including 78 protein-coding, 30 tRNA, and four rRNA genes. The infA gene is pseudogenized. Sixteen genes contain one intron and two genes (clpP and ycf3) have two introns. The phylogenomic analysis conducted in our study reveals that the genus Cardamine, which encompasses C. glechomifolia, exhibits three distinct clades. In order to elucidate the interrelationship among the three clades, it is imperative to conduct additional investigations by augmenting the number of Cardamine samples.
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Stellera chamaejasme L. (SCL) is a perennial herb with demonstrated bioactivities against inflammation and metabolic dysfunction. Adipocyte differentiation is a critical regulator of metabolic homeostasis and a promising target for the treatment of metabolic diseases, so we examined the effects of SCL on adipogenesis. A methanol extract of SCL dose-dependently suppressed intracellular lipid accumulation in adipocyte precursors cultured under differentiation induction conditions and reduced expression of the adipogenic transcription factors PPARγ and C/EBPα as well as the downstream lipogenic genes fatty acid binding protein 4, adiponectin, fatty acid synthase, and stearoyl-CoA desaturase. The extract also promoted precursor cell proliferation and altered expression of the cell cycle regulators cyclin-dependent kinase 4, cyclin E, and cyclin D1. In addition, SCL extract stimulated extracellular signal-regulated kinase (ERK) phosphorylation, while pharmacological inhibition of ERK effectively blocked the inhibitory effects of SCL extract on preadipocyte differentiation. These results suggest that SCL extract contains bioactive compounds that can suppress adipogenesis through modulation of the ERK pathway.
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Adipogénesis , Quinasas MAP Reguladas por Señal Extracelular , Ratones , Animales , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Diferenciación Celular , Metabolismo de los Lípidos , Adipocitos/metabolismo , Células 3T3-L1 , PPAR gamma/metabolismoRESUMEN
Phedimus aizoon has been utilized as a medicinal plant in Asia. However, the production of phytochemical-rich extracts from P. aizoon and the evaluation of their bioactivity are limited. Herein, phytochemical-rich extracts were prepared by ultrasound-assisted extraction of P. aizoon, with a high extraction yield of 16.56%. The extracts contained about 126 mg of phenolics and 31 mg of flavonoids per g of the extracts. The chromatographic analysis (GC-MS and HPLC analyses) identified 19 notable phytochemicals of the extracts from P. aizoon, including pentacosane, hexadecanoic acid, gallic acid, vanillic acid, and quercetin. The gallic acid content of the extracts was relatively high at 2.75 mg/g. The identified compounds are known to have various bioactivities, such as antioxidant, antibacterial, and antifungal activities. In fact, the prepared extracts exhibited antioxidant activity at 24-28% of that of ascorbic acid. In addition, it showed antibacterial activity against both Escherichia coli (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacteria). This study highlights that P. aizoon deserves attention as a natural bioactive substance and emphasizes the need for applications of the extracts from P. aizoon.
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Inflammation is implicated as a cause in many diseases. Most of the anti-inflammatory agents in use are synthetic and there is an unmet need for natural substance-derived anti-inflammatory agents with minimal side effects. Aiouea padiformis belongs to the Lauraceae family and is primarily found in tropical regions. While some members of the Aiouea genus are known to possess anti-inflammatory properties, the anti-inflammatory properties of Aiouea padiformis extract (AP) have not been investigated. In this study, we aimed to examine the anti-inflammatory function of AP through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and elucidate the underlying mechanisms. Treatment with AP inhibited the secretion of interleukin-1 beta (IL-1ß) mediated by NLRP3 inflammasome in J774A.1 and THP-1 cells without affecting the viability. In addition, AP treatment did not influence NF-κB signaling, potassium efflux, or intracellular reactive oxygen species (ROS) production-all of which are associated with NLRP3 inflammasome activation. However, intriguingly, AP treatment significantly reduced the ATPase activity of NLRP3, leading to the inhibition of ASC oligomerization and speck formation. Consistent with cellular experiments, the anti-inflammatory property of AP in vivo was also evaluated using an LPS-induced inflammation model in zebrafish, demonstrating that AP hinders NLRP3 inflammasome activation.
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Lauraceae , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Inflamasomas , Pez Cebra , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Adenosina Trifosfatasas , Extractos Vegetales/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Guarea genus comprises tropical and subtropical terrestrial herbs inhabiting Central and South America. These plants, including Guarea guidonia (L.) Sleumer, have anti-inflammatory, analgesic, antibacterial, antiviral, and immune-enhancing properties. AIM OF THE STUDY: Although various species of the Guarea genus are known for their medicinal properties, comprehensive data on their anti-inflammatory effects remain limited. Therefore, we investigated the NLRP3 inflammasome-inhibiting effects of the Guarea genus in this study. MATERIALS AND METHODS: To evaluate the anti-inflammatory activities of 18 members of the Guarea genus, we treated NLRP3 inflammasome activators with their extracts in LPS-primed J774A.1 and THP-1 cells. Cell viability was determined by water soluble tetrazolium salt (WST) and cytokine production, protein expression, and nuclear fractionation were determined by western blotting. Reactive oxygen species (ROS) production and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization were measured using confocal microscopic analysis. Inflammation-induced zebrafish was used in the in vivo experiments. RESULTS: Among the 18 Guarea members tested, Guarea microcarpa C. DC. extract (GM) exhibited no cytotoxicity and specifically suppressed the activation of the NLRP3 inflammasome, but not of the AIM2 or NLRC4 inflammasomes, by inhibiting the ATPase activity of NLRP3. This was achieved without affecting NF-κB signaling, potassium efflux, or intracellular ROS production, all of which are involved in NLRP3 activation. The reduced ATPase activity of NLRP3 led to decreased ASC oligomerization. Furthermore, GM exhibited anti-inflammatory effects in vivo. Additionally, GM treatment alleviated inflammation at the organismal level in an LPS-induced inflammation model using zebrafish embryos. CONCLUSION: Our results demonstrate the anti-inflammatory effects of GM via suppressing the NLRP3 inflammasome. Therefore, GM can be a potential therapeutic candidate for various inflammatory diseases caused by aberrant NLRP3 inflammasome activation.