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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.
Assuntos
Anti-Inflamatórios , Asma , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Neutrófilos , Espécies Reativas de Oxigênio , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Inflamassomos/metabolismo , Asma/metabolismo , Asma/tratamento farmacológico , Asma/imunologia , Asma/patologia , Camundongos , Anti-Inflamatórios/farmacologia , Humanos , Neutrófilos/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Espécies Reativas de Oxigênio/metabolismo , Lipopolissacarídeos , Quinases Relacionadas a NIMA/metabolismo , Interleucina-1beta/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Modelos Animais de Doenças , Extratos Vegetais/farmacologia , Células THP-1RESUMO
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.
Assuntos
Caryophyllales , Dieta Hiperlipídica , Animais , Camundongos , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Dinâmica Mitocondrial , Insulina , Extratos Vegetais/farmacologiaRESUMO
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.
Assuntos
Lauraceae , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Inflamassomos , Peixe-Zebra , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Adenosina Trifosfatases , Extratos Vegetais/farmacologiaRESUMO
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.
Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peixe-Zebra , Espécies Reativas de Oxigênio/metabolismo , Lipopolissacarídeos/farmacologia , Caspase 1/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , NF-kappa B/metabolismo , Anti-Inflamatórios não Esteroides/uso terapêutico , Adenosina Trifosfatases , Interleucina-1beta/metabolismoRESUMO
Due to the continuous increase in patients with androgenetic alopecia (AGA) and psychological disorders such as depression and anxiety, the demand for hair loss treatment and effective hair growth materials has increased. Terminalia bellirica (Gaertn.) Roxb. (TBE) reportedly exerts anti-inflammatory, hepatoprotective, and antidiabetic effects, among others, but its effects on testosterone (TS)-inhibited hair growth remains unclear. In this study, we evaluated the effects of TBE on TS-induced hair growth regression in human follicle dermal papilla cells (HFDPCs) and C57BL/6 mice. Oral administration of TBE increased TS-induced hair growth retardation. Interestingly, effects were greater when compared with finasteride, a commercial hair loss treatment product. Histological analyses revealed that oral TBE administration increased hair follicles in the dorsal skin of C57BL/6 mice. Additionally, western blotting and immunofluorescence showed that oral TBE administration recovered the TS-induced inhibition of cyclin D1, proliferating cell nuclear antigen (PCNA), and Ki67 expression in vivo. Using in vitro proliferation assays, TBE promoted HFDPC growth, which was suppressed by TS treatment. Thus, TBE may be a promising nutraceutical for hair health as it promoted hair growth in AGA-like in vitro and in vivo models.
Assuntos
Terminalia , Testosterona , Camundongos , Animais , Humanos , Frutas , Extratos Vegetais/farmacologia , Camundongos Endogâmicos C57BL , Alopecia/induzido quimicamente , Alopecia/tratamento farmacológico , Folículo PilosoRESUMO
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.
Assuntos
Anti-Inflamatórios/farmacologia , Caragana/química , Inflamação/tratamento farmacológico , Metanol/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Células Cultivadas , Células HEK293 , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Fator Regulador 3 de Interferon/antagonistas & inibidores , Fator Regulador 3 de Interferon/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/metabolismoRESUMO
Adenium obesum (Forssk.) Roem. & Schult. belonging to the family Apocynaceae, is remarkable for its horticultural and ornamental values, poisonous nature, and medicinal uses. In order to have understanding of cp genome characterization of highly valued medicinal plant, and the evolutionary and systematic relationships, the complete plastome / chloroplast (cp) genome of A. obesum was sequenced. The assembled cp genome of A. obesum was found to be 154,437 bp, with an overall GC content of 38.1%. A total of 127 unique coding genes were annotated including 96 protein-coding genes, 28 tRNA genes, and 3 rRNA genes. The repeat structures were found to comprise of only mononucleotide repeats. The SSR loci are compososed of only A/T bases. The phylogenetic analysis of cp genomes revealed its proximity with Nerium oleander.
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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.
Assuntos
Exercício Físico , Músculo Esquelético , Biorretroalimentação Psicológica , Estudos Transversais , Eletromiografia , Humanos , Masculino , Músculos ParaespinaisRESUMO
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.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Dieta Hiperlipídica , Hiperglicemia/tratamento farmacológico , Metabolismo dos Lipídeos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Extratos Vegetais/uso terapêutico , Viburnum/química , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/patologia , Adipogenia/efeitos dos fármacos , Tecido Adiposo Branco/patologia , Animais , Fármacos Antiobesidade/farmacologia , Biflavonoides/farmacologia , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Fígado Gorduroso/sangue , Fígado Gorduroso/complicações , Fígado Gorduroso/tratamento farmacológico , Comportamento Alimentar , Glucose/metabolismo , Teste de Tolerância a Glucose , Homeostase/efeitos dos fármacos , Hiperglicemia/sangue , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Hipertrofia , Insulina/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Obesidade/sangue , Obesidade/complicações , Tamanho do Órgão/efeitos dos fármacos , Oxirredução , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa japonica Thunb., as an herbal medicine has been used for the treatment of inflammatory diseases in China and Korea. MATERIALS AND METHODS: Ultra performance liquid chromatography-photodiode array-quadrupole time-of-flight mass spectrometer (UPLC-PDA-QTof MS) was used to detect the major phenylethanoid glycosides in the C. japonica extract. BALB/c mice were intraperitoneally sensitized by ovalbumin (OVA) (on days 0 and 7) and challenged by OVA aerosol (on days 11-13) to induce airway inflammatory response. The mice were also administered with C. japonica Thunb. (CJT) (20 and 40 mg/kg Per oral) on days 9-13. CJT pretreatment was conducted in lipopolysaccharide (LPS)-stimulated RAW264.7 or phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells. RESULTS: CJT administration significantly reduced the secretion of Th2 cytokines, TNF-α, IL-6, immunoglobulin E (IgE) and histamine, and the recruitment of eosinophils in an OVA-exposed mice. In histological analyses, the amelioration of inflammatory cell influx and mucus secretion were observed with CJT. The OVA-induced airway hyperresponsiveness (AHR), iNOS expression and NF-κB activation were effectively suppressed by CJT administration. In addition, CJT led to the upregulation of HO-1 expression. In an in vitro study, CJT pretreatment suppressed the LPS-induced TNF-α secretion in RAW264.7 cells and attenuated the PMA-induced IL-6, IL-8 and MCP-1 secretion in A549 cells. These effects were accompanied by downregulated NF-κB phosphorylation and by upregulated HO-1 expression. CONCLUSION: These results suggested that CJT has protective activity against OVA-induced airway inflammation via downregulation of NF-κB activation and upregulation of HO-1, suggesting that CJT has preventive potential for the development of allergic asthma.
Assuntos
Antiasmáticos/farmacologia , Anti-Inflamatórios/farmacologia , Asma/prevenção & controle , Hiper-Reatividade Brônquica/prevenção & controle , Callicarpa , Heme Oxigenase-1/metabolismo , Pulmão/efeitos dos fármacos , Proteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Células A549 , Animais , Antiasmáticos/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Asma/induzido quimicamente , Asma/enzimologia , Asma/fisiopatologia , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/enzimologia , Hiper-Reatividade Brônquica/fisiopatologia , Broncoconstrição/efeitos dos fármacos , Callicarpa/química , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Pulmão/enzimologia , Pulmão/fisiopatologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , Transdução de Sinais , Regulação para CimaRESUMO
The complete chloroplast genome sequences of vulnerable medicinal plant Saraca asoca (Roxb.) Willd. (Fabaceae) was sequenced. A total of 5,206,216,851 paired-end filtered reads of 151 bp were obtained. The plastome length (including LSC, SSC, IRa, and IRb) was 137,743 bp (GC content: 35.26%). A total of 126 coding genes which includes 97 CDS, 24 tRNA, and five rRNA genes were annotated. The phylogenetic analysis attempts to establish molecular signature in order to differentiate genuine sample of S. asoca from its adulterants easily.
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A number of species of the genus Trichilia (Meliaceae) exhibit anti-inflammatory effects. However, the effect of Trichilia martiana C. DC. (TM) on lipopolysaccharide (LPS)-induced inflammation has not, to the best of our knowledge, yet been determined. Therefore, in the present study, the antiinflammatory effect of TM on LPS-stimulated RAW264.7 macrophages was evaluated. The ethanol extract of TM (TMEE) significantly inhibited LPS-induced nitric oxide (NO), prostaglandin 2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). TMEE also reduced the levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß and IL-6. The upregulation of mitogen-activated protein kinases (MAPKs) and NF-κB activation was revealed to be downregulated following TMEE pretreatment. Furthermore, TMEE was indicated to lead to the nucleus translocation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1). In H292 airway epithelial cells, the pretreatment of TMEE significantly downregulated the production of LPS-stimulated IL-1ß, and TMEE was indicated to increase the expression of HO-1. In animal models exhibiting LPS-induced acute lung injury (ALI), treatment with TMEE reduced the levels of macrophages influx and TNF-α production in the bronchoalveolar lavage fluid (BALF) of ALI mice. Additionally, TMEE significantly downregulated the activation of ERK, JNK and IκB, and upregulated the expression of HO-1 in the lungs of ALI mice. In conclusion, the results of the current study demonstrated that TMEE could exert a regulatory role in the prevention or treatment of the endotoxin-mediated inflammatory response.
Assuntos
Anti-Inflamatórios/farmacologia , Células Epiteliais/efeitos dos fármacos , Lipopolissacarídeos/efeitos adversos , Macrófagos/efeitos dos fármacos , Meliaceae/química , Extratos Vegetais/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Ciclo-Oxigenase 2 , Citocinas/metabolismo , Modelos Animais de Doenças , Heme Oxigenase-1 , Inflamação/tratamento farmacológico , Interleucina-1beta , Interleucina-6 , Pulmão , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Prostaglandinas , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUD: Although the effect of exercise in patients during the subacute and/or chronic subacromial impingement syndrome has been reported, only a few studies have examined the effect of pain free exercise in the acute phase of this disorder. OBJECTIVE: To compare the effect of training using the Neurac technique which combines body segments suspension and vibration vs. manual therapy, on various relevant outcome parameters in patients with acute subacromial impingement syndrome (PASIS). METHOD: Twenty-six patients underwent a 4 week intervention program. Using random assignment, half of the patients were treated using the Neurac device while the other half was treated using manual therapy. The outcome parameters consisted of shoulder pain, shoulder function, range of motion (ROM) and the isokinetic strength of the external and internal rotators at 60 and 180∘/s. RESULTS: Following either modes of interventions, the pain, function, and ROM improved significantly compared to pre-intervention levels in both groups. Time-by-group interaction was observed for the rotational strength which increased significantly and exclusively in the Neurac group. CONCLUSIONS: Given its positive effect on shoulder pain, function, ROM and the isokinetic strength of the external and internal rotators, we recommend the application of the Neurac technique in PASIS.
Assuntos
Manipulações Musculoesqueléticas/métodos , Modalidades de Fisioterapia , Amplitude de Movimento Articular/fisiologia , Síndrome de Colisão do Ombro/terapia , Vibração/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ombro/fisiopatologia , Síndrome de Colisão do Ombro/fisiopatologia , Dor de Ombro/fisiopatologia , Método Simples-Cego , Resultado do TratamentoRESUMO
BACKGROUND: Spinal muscular atrophy (SMA) is a rare neuromuscular disease and a leading genetic cause of infant mortality. SMA is caused primarily by the deletion of the survival motor neuron 1 (SMN1) gene, which leaves the duplicate gene SMN2 as the sole source of SMN protein. The splicing defect (exon 7 skipping) of SMN2 leads to an insufficient amount of SMN protein. Therefore, correcting this SMN2 splicing defect is considered to be a promising approach for the treatment of SMA. PURPOSE: This study aimed to identify active compounds and extracts from plant resources to rescue SMA phenotypes through the correction of SMN2 splicing. STUDY DESIGN: Of available plant resources, candidates with SMA-related traditional medicine information were selected for screening using a robust luciferase-based SMN2 splicing reporter. Primary hits were further evaluated for their ability to correct the splicing defect and resultant increase of SMN activity in SMA patient-derived fibroblasts. Confirmed hits were finally tested to determine the beneficial effects on the severe Δ7 SMA mouse. METHODS: SMN2 splicing was analyzed using a luciferase-based SMN2 splicing reporter and subsequent RT-PCR of SMN2 mRNAs. SMA phenotypes were evaluated by the survival, body weights, and righting reflex of Δ7 SMA mice. RESULTS: In a screen of 492 selected plant extracts, we found that Brucea javanica extract and its major constituent Bruceine D have SMN2 splicing-correcting activity. Their ability to correct the splicing defect and the resulting increased SMN activity were further confirmed in SMA fibroblasts. Importantly, both B. javanica and Bruceine D noticeably improved the phenotypic defects, especially muscle function, in SMA mice. Reduced expression of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) contributed to the correction of splicing by B. javanica. CONCLUSION: Our work revealed that B. javanica and Bruceine D correct the SMN2 splicing defect and improve the symptoms of SMA in mice. These resources will provide another possibility for development of a plant-derived SMA drug candidate.
Assuntos
Brucea/química , Atrofia Muscular Espinal/tratamento farmacológico , Extratos Vegetais/farmacologia , Quassinas/farmacologia , Processamento Alternativo , Animais , Linhagem Celular , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Éxons , Humanos , Camundongos Transgênicos , Atrofia Muscular Espinal/genética , Extratos Vegetais/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína 2 de Sobrevivência do Neurônio Motor/genéticaRESUMO
Cedrela odorata L. is a native plant of the Amazon region. The bark is used in folk remedies for the treatment of diarrhea, vomiting, fever and inflammation. Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease accompanied by itching. It is a complex disease involving environmental factors and genetic factors. In the present study, the anti-inflammatory and anti-allergic effects of C. odorata L. methanol extract (COEE) on tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated HaCaT keratinocyte cells were investigated. ELISA and RT-PCR analysis revealed that the extract had anti-inflammatory effects, and reduced the interleukin (IL)-6 and IL-8 levels of the HaCaT cells. In addition, COEE exhibited anti-allergic effects, comprising a reduction in the thymus and activation-regulated chemokine and macrophage-derived chemokine levels. In addition, pathway analysis and comparison with Bay11-7082 indicated that these effects are due to the inhibition of nuclear factor (NF)-κB in TNF-α/IFN-γ-induced HaCaT cells. Therefore, the results of the present study suggest that COEE has anti-inflammatory and anti-allergic properties in TNF-α and IFN-γ-stimulated HaCaT cells, which are associated with the inhibition of pro-inflammatory cytokines and chemokines via the NF-κB pathway.
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Although neutral pelvic alignment is important for hip abduction exercises, studies exploring objectively monitored pelvic alignment on the gluteus medius (Gmed) muscle activity during hip abduction exercises, especially under weight-bearing (WB) conditions, are limited. Therefore, we examined the effects of real-time visual biofeedback (RVBF) of pelvic movement on electromyographic (EMG) activity of hip muscles and lateral pelvic tilt during unilateral WB and side-lying hip abductions. Fifteen male participants performed unilateral WB and side-lying hip abduction exercises with and without RVBF. Under the RVBF condition, participants monitored pelvic movements in real time during hip abduction exercises. EMG activity of Gmed and quadratus lumborum (QL) as well as lateral pelvic tilt angle were recorded during each hip abduction exercise. Gmed EMG activity increased, while lateral pelvic tilt decreased during both hip abduction exercises with RVBF (pâ¯<â¯0.05). Additionally, the changes in Gmed activity, the Gmed/QL activity ratio, and the lateral pelvic tilt angle under RVBF were greater during unilateral WB hip abduction than during side-lying hip abduction (pâ¯<â¯0.05). These results suggest that RVBF of pelvic movement could be useful to strengthen Gmed and prevent compensatory lateral pelvic movement during hip abduction exercises, especially in the unilateral WB position.
Assuntos
Biorretroalimentação Psicológica , Retroalimentação Sensorial , Articulação do Quadril/fisiologia , Músculo Esquelético/fisiologia , Pelve/fisiologia , Suporte de Carga , Músculos Abdominais , Adulto , Nádegas , Eletrodos , Eletromiografia , Exercício Físico , Quadril/fisiologia , Humanos , Masculino , Movimento , Postura , Coxa da Perna , Adulto JovemRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The ethnobotanical survey was carried out in the Bac Huong Hoa Nature Reserve (BHHNR), Vietnam. The Van Kieu ethnic group, the inhabitant of Nature Reserve, is rich in knowledge about the medicinal plants found in the Nature Reserve. However, their knowledge is less documented. AIM OF THE STUDY: The present study was conducted to document the use of medicinal plants, plant parts used, mode of preparation and delivery by the ethnic group of Van Kieu. The study also aimed at comparing the information generated by this study with the previously published Dictionary of Vietnam Medicinal plants (DVM). MATERIALS AND METHODS: The information was collected through semi-structured and unstructured interviews. The interviews were conducted from April 2016 to March 2017. The number of informants involved in the survey was 93 belonging to age group of 20-81. Species Use-Reports (UR) were analyzed to determine the plant importance in the local and the Informant Consensus Factor (FIC). Local plant uses were listed and compared with the previously published data from Vietnam. RESULTS: Comprehensively 355 Use-Reports were documented in this study. A total of 111 medicinal plant species belonging to 102 genera and 46 families were reported. Out of 46 families, Euphorbiaceae (10 species), Compositae and Leguminosae (9 species each), Apocynaceae (7 species), Rutaceae and Rubiaceae (5 species each) were the dominant families. Leaves were the most frequently used plant part (43.1%) in the preparation of medicines. The most frequent preparation method was decoction (49%) while the oral route of administration (51%) was the most commonly mentioned mode of administration. Artocarpus heterophyllus Lam., Chromolaena odorata (L.) R.M.King & H.Rob., Blumea balsamifera (L.) DC., Psidium guajava L. and Catunaregam spinosa (Thunb.) Tirveng. were shown to be the most useful plants as indicated by their relatively high UR. Eight medicinal plants (7.21%) used by Van Kieu ethnic people have not been previously reported in DVM. CONCLUSION: The Van Kieu ethnic group holds valuable knowledge about uses of medicinal plant resources which is inherited through generations however this knowledge was not documented. The study highlights the need for documenting and publicizing the traditional medicinal knowledge which will provide basic data for further research and conservation.
Assuntos
Magnoliopsida , Medicina Tradicional , Plantas Medicinais , Adulto , Idoso , Idoso de 80 Anos ou mais , Etnicidade , Etnobotânica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fitoterapia , Inquéritos e Questionários , Vietnã , Adulto JovemRESUMO
To broaden and delve into the genomic information of Clausena excavata, an important medicinal plant in many Asian countries, RNA sequencing (RNA-seq) analysis was performed and a total of 16,638 non-redundant unigenes (≥ 300 bp) with an average length of 755 bp were generated by de novo assembly from 17,580,456 trimmed clear reads. The functional categorization of the identified unigenes by a gene ontology (GO) term resulted in 2305 genes in the cellular component, 5577 in the biological processes, and 8056 in the molecular functions, respectively. The top sub-category in biological processes was the metabolic process with 4374 genes. Among annotated genes, 3006 were mapped to 123 metabolic pathways by the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis tool. The search for simple sequence repeats (SSRs) resulted in 845 SSRs from 749 SSR-containing unigenes and the most abundant SSR motifs was AAG/CTT with 179 occurrences. Twelve SSR markers were tested for cross transferability among five Clausena species; eight of them exhibited polymorphism. Taken together, these data provide valuable resources for genomic or genetic studies of Clausena species and other relative studies. The transcriptome shotgun assembly data have been deposited at DDBJ/EMBL/GenBank under the accession GGEM00000000.
RESUMO
Induction of apoptosis through activation of the TRAIL pathway is considered to be a promising anticancer strategy due to its ability to selectively induce apoptosis in cancer cells. However, the ability of cancer cells to acquire TRAIL resistance has limited the clinical translation of this approach. We previously reported that the TOR signaling pathway regulator-like (TIPRL) protein contributes to the resistance to TRAIL-induced apoptosis by inhibiting the MKK7-c-Jun N-terminal kinase (JNK) pathway via MKK7TIPRL interaction. In the present study, we identified Tussilago farfara L. (TF) as a novel TRAIL sensitizer among 500 natural products using an ELISA system that specifically detects the MKK7-TIPRL interaction, and we validated candidates by GST-pull down assay. Co-treatment of Huh7 cells with TF and TRAIL induced apoptosis via inhibition of the MKK7-TIPRL interaction and an increase in MKK7/JNK phosphorylation. This is the first report to describe TF as a novel TRAIL sensitizer, unveiling a potentially novel therapeutic strategy in cancer therapy.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tussilago/química , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologiaRESUMO
A putative cytochrome P450 gene from chili pepper, Capsicum annuum L. Bukang cytochrome P450 (CaCYP1), was identified using cDNA microarray analysis of gene expression following induction of the leaf hypersensitive response by inoculation of pepper plants with the non-host pathogen Xanthomonas axonopodis pv. glycines 8ra. The full-length cDNA of CaCYP1 encoded a protein of 514 amino acid residues, which contained a putative hydrophobic membrane anchoring domain in the N-terminal region, and a heme-binding motif in the C-terminal region. Analysis of the deduced amino acid sequence of CaCYP1 revealed that it has high homology to Arabidopsis CYP89A5, the function of which is unknown. Expression of CaCYP1 was preferentially increased in pepper plants in response to non-host pathogen inoculation and also during the host resistance response. CaCYP1 expression also increased following treatment with salicylic acid and abscisic acid, while treatment with ethylene had a mild effect. Using a virus-induced gene silencing-based reverse genetics approach, we demonstrated that suppression of CaCYP1 results in enhanced susceptibility to bacterial pathogens. Interestingly, gene silencing of CaCYP1 in pepper plants resulted in the reduced expression of the defense-related genes CaLTP1, CaSIG4, and Cadhn. Our results indicated that CaCYP1, a novel cytochrome P450 in pepper plants, may play a role in plant defense response pathways that involve salicylic acid and abscisic acid signaling pathways.