Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 18.325
Filtrar
1.
Medicine (Baltimore) ; 100(3): e23986, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33545988

RESUMEN

ABSTRACT: Rosacea is a facial chronic inflammatory skin disease with immune and vascular system dysfunction. Paeoniflorin (PF) is a traditional Chinese medicine with anti-inflammatory properties. However, its effects on rosacea remain unknown. Here, we investigated the mechanisms through which PF inhibits the macrophage-related rosacea-like inflammatory response. Immunohistochemical methods were used to detect differences in the inflammatory response and degree of macrophage infiltration in granulomatous rosacea lesions and their peripheral areas. Cell Counting Kit-8 was used to determine the cytotoxicity of PF towards RAW 264.7 cells. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to measure the influence of PF on mRNA and protein expression levels of suppressor of cytokine signaling 3 (SOCS3), apoptosis signal-regulating kinase 1 (ASK1)-p38, Toll-like receptor 2, and cathelicidin antimicrobial peptide ( or LL37) in the lipopolysaccharide (LPS)-induced macrophage-related rosacea-like inflammatory response of RAW 264.7 cells. Inflammatory cell infiltration was more pronounced in granulomatous rosacea lesions than in peripheral areas. LL37 expression increased significantly, and the infiltration of a large number of CD68+ macrophages was observed in the lesions. PF promoted SOCS3 expression in RAW 264.7 cells and inhibited the LPS-induced increase in toll-like receptor 2 and LL37 expression through the ASK1-p38 cascade, thereby alleviating the macrophage-related rosacea-like inflammatory response. These changes could be abrogated by SOCS3 siRNA in vitro.In conclusion, the pathogenesis of rosacea involves abnormal macrophage infiltration within the lesions. PF inhibits the macrophage-related rosacea-like inflammatory response through the SOCS3-ASK1-p38 pathway, demonstrating its potential application as a novel drug for rosacea therapy.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Glucósidos/farmacología , MAP Quinasa Quinasa Quinasa 5/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Monoterpenos/farmacología , Rosácea/tratamiento farmacológico , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Animales , Técnicas de Cultivo de Célula , Humanos , Macrófagos/metabolismo , Ratones , Células RAW 264.7 , Piel/citología
2.
Int J Nanomedicine ; 16: 133-145, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33447032

RESUMEN

Background: Rheumatoid arthritis (RA) is an autoimmune disease that underlies chronic inflammation of the synovial membrane. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat RA. However, a long list of adverse events associated with long-term treatment regimens with NSAIDs negatively influences patient compliance and therapeutic outcomes. Aim: The aim of this work was to achieve site-specific delivery of celecoxib-loaded spanlastic nano-vesicle-based delivery system to the inflamed joints, avoiding systemic administration of large doses. Methodology: To develop spanlastic nanovesicles for transdermal delivery of celecoxib, modified injection method was adopted using Tween 80 or Brij as edge activators. Entrapment efficiency, vesicle size, ex vivo permeation, and morphology of the prepared nano-vesicles were characterized. Carbopol-based gels containing the selected formulations were prepared, and their clarity, pH, rheological performance, and ex vivo permeation were characterized. Celecoxib-loaded niosomes and noisome-containing gels were developed for comparison. The in vivo efficacy of the selected formulations was evaluated in a rat model of Freund's complete adjuvant-induced arthritis. Different inflammatory markers including TNF-α, NF-кB and COX-2 were assessed in paw tissue before and after treatment. Results: The size and entrapment efficiency of the selected spanlastic nano-vesicle formulation were 112.5 ± 3.6 nm, and 83.6 ± 2.3%, respectively. This formulation has shown the highest transdermal flux and permeability coefficient compared to the other investigated formulations. The spanlastics-containing gel of celecoxib has shown transdermal flux of 6.9 ± 0.25 µg/cm2/hr while the celecoxib niosomes-containing gel and unprocessed celecoxib-loaded gel have shown 5.2 ± 0.12 µg/cm2/hr and 0.64 ± 0.09 µg/cm2/hr, respectively. In the animal model of RA, the celecoxib-loaded spanlastics-containing gel significantly reduced edema circumference and significantly suppressed TNF-α, NF-кB and COX-2 levels compared to the niosomes-containing gel, the marketed diclofenac sodium gel, and unprocessed celecoxib-loaded gel. Conclusion: The spanlastic nano-vesicle-containing gel represents a more efficient site-specific treatment for topical treatment of chronic inflammation like RA, compared to commercial and other conventional alternatives.


Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Celecoxib/uso terapéutico , Ciclooxigenasa 2/metabolismo , Regulación hacia Abajo , FN-kappa B/metabolismo , Nanopartículas/química , Factor de Necrosis Tumoral alfa/metabolismo , Administración Cutánea , Administración Tópica , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/genética , Celecoxib/farmacología , Ciclooxigenasa 2/genética , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Adyuvante de Freund , Regulación de la Expresión Génica/efectos de los fármacos , Cinética , Liposomas , Masculino , Ratones , FN-kappa B/genética , Tamaño de la Partícula , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Wistar , Reología , Absorción Cutánea/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética
3.
Phytomedicine ; 80: 153385, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33091854

RESUMEN

BACKGROUND: Microglia-mediated neuroinflammation is one of the most prominent characteristics of multiple sclerosis (MS), a chronic demyelination disease. As one of the main active ingredients in Astragali radix, total flavonoids of Astragalus (TFA) has multiple pharmacological effects such as immunomodulation, anti-inflammation and and anti-tumor. However, little is known about whether TFA could inhibit microglia-mediated neuroinflammation in MS. PURPOSE: This study was aimed to elucidate whether TFA could inhibit microglia-mediated neuroinflammation in MS. STUDY DESIGN: In the present study, we explored the protective effect of TFA on experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in mice for the first time, and discussed its mechanism from the aspect of anti-microglia-mediated neuroinflammation. METHODS: The mice received oral administration of TFA (25 and 50 mg/kg) daily from two days before immunization and continued until day 21 post-immunization. The effect of TFA on EAE in mice and its mechanism were investigated by ELISA, Western blot, real-time PCR, luciferase reporter assay, histopathology and immunohistochemistry. RESULTS: TFA were shown to alleviate the severity of EAE in mice. It inhibited the excessive activation of microglia both in spinal cords of EAE mice and in LPS-stimulated BV-2 cells, evidenced by weakening the production of inflammatory mediators such as NO, TNF-α, IL-6, and IL-1ß markedly at either protein or mRNA level. Further study demonstrated that TFA repressed the phosphorylation, nuclear translocation and transcriptional activity of NFκB, and inhibited the activation of AKT and JNK signaling in BV-2 cells induced by LPS. The agonists of AKT and JNK, anisomycin and SC79, could partly abolish the inhibitory effect of TFA on the production of inflammatory mediators in BV-2 cells induced by LPS. CONCLUSIONS: Taken together, our results clarified that TFA inhibited microglia-mediated inflammation in EAE mice probably through deactivating JNK/AKT/NFκB signaling pathways. The novel findings may lay a theoretical foundation for the clinical application of TFA in the treatment of MS.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Astrágalo (Planta)/química , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Flavonoides/farmacología , Microglía/efectos de los fármacos , Animales , Línea Celular , Citocinas/metabolismo , Encefalomielitis Autoinmune Experimental/metabolismo , Femenino , Flavonoides/química , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones Endogámicos C57BL , Microglía/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/fisiopatología
4.
Phytomedicine ; 80: 153382, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33113506

RESUMEN

BACKGROUND: Although gastroprotective drugs have been used for peptic ulcer disease prevention and treatment, side effects have been observed. Finding a safe and effective treatment strategy is important. PURPOSE: Edible Trichodesma khasianum (T. khasianum) Clarke leaves are considered to protect against peptic ulcers. However, scientific evidence of this effect of T. khasianum Clarke leaves remains limited. STUDY DESIGN/METHODS: In this study, we aimed to evaluate the effect of T. khasianum Clarke leaves on ethanol-induced gastric injury and gut microbiota using RAW 264.7 cells, RGM-1 cells, and BALB/c mice, respectively. RESULT: The rosmarinic acid was identified as the major component of T. khasianum Clarke leaves extracted by 80% ethanol (80EETC). The results showed that 80EETC suppressed inflammatory mediator protein levels in LPS-induced RAW 264.7 cells. Additionally, heat shock protein expression, antiapoptotic ability, and wound healing migration capability were increased by 80EETC pretreatment in RGM-1 cells with the ethanol-induced injury. Remarkably, pretreatment with 80EETC (150 mg/kg b.w.) promoted gastric mucosal healing by decreasing oxidative stress, inflammatory response, proapoptotic protein expression, and gastric mucosa damage in ethanol-induced gastric injury in mice. Crucially, no liver or kidney toxicities were observed by 80EETC oral gavage. Moreover, 80EETC increased gut microbiota diversity and short-chain fatty acid production. CONCLUSION: Our results illustrated the remarkable gastroprotective effect by 80EETC treatment in vitro and in vivo. These findings are the first to demonstrate the powerful protective effect of T. khasianum Clarke leaves against gastric mucosal injury development.


Asunto(s)
Boraginaceae/química , Cinamatos/farmacología , Depsidos/farmacología , Mucosa Gástrica/efectos de los fármacos , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Administración Oral , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/metabolismo , Cinamatos/análisis , Depsidos/análisis , Etanol/toxicidad , Ácidos Grasos Volátiles/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Estrés Oxidativo/efectos de los fármacos , Úlcera Péptica/prevención & control , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Hojas de la Planta/química , Sustancias Protectoras/química , Células RAW 264.7
5.
Phytomedicine ; 80: 153398, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33130474

RESUMEN

BACKGROUND: Celastrol, a pentacyclic triterpenoid quinonemethide isolated from several spp. of Celastraceae family, exhibits anti-inflammatory activities in a variety of diseases including arthritis. PURPOSE: This study aims to investigate whether the inhibition of NLRP3 inflammasome is engaged in the anti-inflammatory activities of celastrol and delineate the underlying mechanism. METHODS: The influence of celastrol on NLRP3 inflammasome activation was firstly studied in lipopolysaccharide (LPS)-primed mouse bone marrow-derived macrophages (BMDMs) and phorbol 12-myristate 13-acetate (PMA)-primed THP-1 cells treated with nigericin. Reconstituted inflammasome was also established by co-transfecting NLRP3, ASC, pro-caspase-1 and pro-IL-1ß in HEK293T cells. The changes of inflammasome components including NLRP3, ASC, pro-caspase-1/caspase-1 and pro-IL-1ß/IL-1ß were examined by enzyme-linked immunosorbent assay (ELISA), western blotting and immunofluorescence. Furthermore, Propionibacterium acnes (P. acnes)/LPS-induced liver injury and monosodium urate (MSU)-induced gouty arthritis in mice were employed in vivo to validate the inhibitory effect of celastrol on NLRP3 inflammasome. RESULTS: Celastrol significantly suppressed the cleavage of pro-caspase-1 and pro-IL-1ß, while not affecting the protein expressions of NLRP3, ASC, pro-caspase-1 and pro-IL-1ß in THP-1 cells, BMDMs and HEK293T cells. Celastrol suppressed NLRP3 inflammasome activation and alleviated P. acnes/LPS-induced liver damage and MSU-induced gouty arthritis. Mechanism study revealed that celastrol could interdict K63 deubiquitination of NLRP3, which may concern interaction of celastrol and BRCA1/BRCA2-containing complex subunit 3 (BRCC3), and thereby prohibited the formation of NLRP3, ASC and pro-caspase-1 complex to block the generation of mature IL-1ß. CONCLUSION: Celastrol suppresses NLRP3 inflammasome activation in P. acnes/LPS-induced liver damage and MSU-induced gouty arthritis via inhibiting K63 deubiquitination of NLRP3, which presents a novel insight into inhibition of celastrol on NLRP3 inflammasome and provides more evidences for its application in the therapy of inflammation-related diseases.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Artritis Gotosa/tratamiento farmacológico , Hígado/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Triterpenos/farmacología , Animales , Artritis Gotosa/inducido químicamente , Artritis Gotosa/metabolismo , Células HEK293 , Humanos , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Lipopolisacáridos/toxicidad , Hígado/microbiología , Hígado/patología , Lisina/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Mutantes , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Propionibacterium acnes/patogenicidad , Células THP-1 , Ubiquitinación/efectos de los fármacos , Ácido Úrico/toxicidad
6.
Phytomedicine ; 80: 153400, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33157413

RESUMEN

BACKGROUND: Vascular Endothelial Growth Factors (VEGFs) are a group of growth factor in regulating development and maintenance of blood capillary. The VEGF family members include VEGF-A, placenta growth factor (PGF), VEGF-B, VEGF-C and VEGF-D. VEGF receptor activation leads to multiple complex signaling pathways, particularly in inducing angiogenesis. Besides, VEGF is produced by macrophages and T cells, which is playing roles in inflammation. In macrophages, VEGF receptor-3 (VEGFR-3) and its ligand VEGF-C are known to attenuate the release of pro-inflammatory cytokines. METHODS: Immunoprecipitation and molecular docking assays showed the binding interaction of kaempferol-3-O-rutinoside and VEGF-C. Western blotting and qRT-PCR methods were applied to explore the potentiating effect of kaempferol-3-O-rutinoside in VEGF-C-mediated expressions of proteins and genes in endothelial cells and LPS-induced macrophages. Enzyme-linked immunosorbent assay (ELISA) was employed to reveal the release of proinflammatory cytokines in LPS-induced macrophages. Immunofluorescence assay was performed to determine the effect of kaempferol-3-O-rutinoside in regulating nuclear translocation of NF-κB p65 subunit in the VEGF-C-treated cultures. In addition, Transwell® motility assay was applied to detect the ability of cell migration after drug treatment in LPS-induced macrophages. RESULTS: We identified kaempferol-3-O-rutinoside, a flavonoid commonly found in vegetable and fruit, was able to act on cultured macrophages in inhibiting inflammatory response, and the inhibition was mediated by its specific binding to VEGF-C. The kaempferol-3-O-rutinoside-bound VEGF-C showed high potency to trigger the receptor activation. In LPS-treated cultured macrophages, applied kaempferol-3-O-rutinoside potentiated inhibitory effects of exogenous applied VEGF-C on the secretions of pro-inflammatory cytokines, i.e. IL-6 and TNF-α, as well as expressions of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). This inhibition was in parallel to transcription and translocation of NF-κB. Moreover, the binding of kaempferol-3-O-rutinoside with VEGF-C suppressed the LPS-induced migration of macrophage. CONCLUSION: Taken together, our results suggested the pharmacological roles of kaempferol-3-O-rutinoside in VEGF-C-mediated anti-inflammation.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Quempferoles/metabolismo , Quempferoles/farmacología , Factor C de Crecimiento Endotelial Vascular/metabolismo , Factor C de Crecimiento Endotelial Vascular/farmacología , Animales , Antiinflamatorios no Esteroideos/química , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Quempferoles/química , Lipopolisacáridos/toxicidad , Macrófagos/efectos de los fármacos , Ratones , Simulación del Acoplamiento Molecular , FN-kappa B/genética , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Células RAW 264.7
7.
Phytomedicine ; 80: 153402, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33203590

RESUMEN

BACKGROUND: Although great achievements have been made in the field of cancer therapy, chemotherapy and radiotherapy remain the mainstay cancer therapeutic modalities. However, they are associated with various side effects, including cardiocytotoxicity, nephrotoxicity, myelosuppression, neurotoxicity, hepatotoxicity, gastrointestinal toxicity, mucositis, and alopecia, which severely affect the quality of life of cancer patients. Plants harbor a great chemical diversity and flexible biological properties that are well-compatible with their use as adjuvant therapy in reducing the side effects of cancer therapy. PURPOSE: This review aimed to comprehensively summarize the molecular mechanisms by which phytochemicals ameliorate the side effects of cancer therapies and their potential clinical applications. METHODS: We obtained information from PubMed, Science Direct, Web of Science, and Google scholar, and introduced the molecular mechanisms by which chemotherapeutic drugs and irradiation induce toxic side effects. Accordingly, we summarized the underlying mechanisms of representative phytochemicals in reducing these side effects. RESULTS: Representative phytochemicals exhibit a great potential in reducing the side effects of chemotherapy and radiotherapy due to their broad range of biological activities, including antioxidation, antimutagenesis, anti-inflammation, myeloprotection, and immunomodulation. However, since a majority of the phytochemicals have only been subjected to preclinical studies, clinical trials are imperative to comprehensively evaluate their therapeutic values. CONCLUSION: This review highlights that phytochemicals have interesting properties in relieving the side effects of chemotherapy and radiotherapy. Future studies are required to explore the clinical benefits of these phytochemicals for exploitation in chemotherapy and radiotherapy.


Asunto(s)
Antineoplásicos/efectos adversos , Fitoquímicos/farmacología , Sustancias Protectoras/farmacología , Radioterapia/efectos adversos , Animales , Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Estrés Oxidativo/efectos de los fármacos , Traumatismos por Radiación/prevención & control
8.
Food Chem ; 339: 128159, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33152898

RESUMEN

During production in Chinese baijiu fermentation process, huge amounts of the by-product vinasse are generated and generally utilized as low-value animal feed. We applied alkaline extraction in combination with ultrasonication to recover vinasse proteins, which were then hydrolyzed by complex protease Corolase PP for 8 h to obtain peptide fractions (VPH-1, -2, -3) displaying high DPPH radical scavenging activity. VPH-3 (<3 kDa) separated by ultrafiltration had EC50 values lower than those of VPH-1 and -2 for reactive oxygen species (ROS) and reactive nitrogen species (RNS) radicals, and significantly inhibited production of NO and pro-inflammatory cytokines in LPS-stimulated RAW264.7 macrophage cells. Active peptides and their amino acid sequences were identified by LC-MS/MS analysis, and five synthesized peptides (particularly KLPDHPKLPK and VDVPVKVPYS) displayed strong anti-inflammatory activity at concentration 0.25 mg/mL. These findings will be useful in future commercial development of baijiu vinasse, including application as a new source of bioactive peptides.


Asunto(s)
Bebidas Alcohólicas , Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Péptidos/farmacología , Animales , Antiinflamatorios no Esteroideos/química , Antioxidantes/química , Cromatografía Liquida , Evaluación Preclínica de Medicamentos , Hidrólisis , Ratones , Péptidos/análisis , Péptidos/química , Proteínas de Plantas/análisis , Proteínas de Plantas/farmacología , Hidrolisados de Proteína/análisis , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacología , Células RAW 264.7 , Especies Reactivas de Oxígeno , Espectrometría de Masas en Tándem
9.
Phytomedicine ; 81: 153411, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33310307

RESUMEN

BACKGROUND: Nodakenin, a coumarin glucoside isolated from the roots of Angelica biserrata, has been reported to have anti-inflammatory, antibacterial, anticancer effects. However, despite these studies, the potential liver protective effects of nodakenin in inflammatory liver injury models have not been reported. METHODS: A mouse model of inflammatory liver injury was induced by injection of lipopolysaccharide (LPS) (15 mg/kg, intraperitoneally (i.p)). Liver tissue AST, ALT, ROS, T-GSH and T-SOD were analyzed by ELISA. The concentrations of TNF-α, IL-6, and IL-1ß in serum of LPS-induced inflammatory liver injury mice were analyzed. The mRNA expression levels of GPx1, catalase, SOD1, SOD2, TNF-α, IL-6, IL-1ß, iNOS and COX-2 were analyzed using real-time PCR. The expressions of MAPK, IRF3, NF-κB, Nrf2, HO-1, caspase-3 and caspase-7 were analyzed using western blotting. Liver tissue was stained with IHC to confirm NF-κB, Nrf-2, HO-1, caspase-3, Bax, and Bcl2. Tunnel analysis was performed to confirm the fragmented nuclear DNA characteristics of apoptosis. RESULTS: The administration of nodakenin (10 and 30 mg/kg) reduced serum aminotransferase levels compared to LPS-induced liver damage and significantly improved the oxidative state of liver tissue and pathological damage. Moreover, inhibited the phosphorylation of transforming growth factor beta (TGF-ß)-activated kinase (TAK)-1 in LPS-induced inflammatory liver injury model, and significantly inhibited the transcriptional of nuclear factor-kappa B (NF-kB) and the secretion of pro-inflammatory mediators. In addition nodakenin pre-treatment also attenuated hepatocyte death by regulating apoptosis-related mitochondrial proteins, such as cysteinyl aspartate specific proteinase 3 (caspase 3), poly (ADP-ribose) polymerase (PARP), B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). CONCLUSION: Our findings suggest that nodakenin has anti-inflammatory, anti-oxidant and anti-apoptotic activity and may be an adjunctive prevention agent for liver injury.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Cumarinas/farmacología , Glucósidos/farmacología , Hepatitis Animal/tratamiento farmacológico , Lipopolisacáridos/toxicidad , Animales , Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citocinas/sangre , Citocinas/genética , Enzimas/metabolismo , Hepatitis Animal/metabolismo , Hepatitis Animal/patología , Masculino , Ratones Endogámicos ICR , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología
10.
Phytomedicine ; 80: 153372, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33113505

RESUMEN

BACKGROUND: Feiyangchangweiyan capsule (FYC) is a traditional Chinese medicine formulation used in the clinical treatment of acute and chronic gastroenteritis and bacterial dysentery. However, the effect of FYC on ulcerative colitis (UC) and the mechanism thereof remains unknown. PURPOSE: To investigate the protective effect of FYC on UC mice induced by dextran sulfate sodium and illustrate the potential mechanism of this effect. METHODS: Here, we established a model of UC mice by dextran sulfate sodium and administered with FYC. The disease activity index (DAI), colon length, myeloperoxidase (MPO) content in serum, pathological structure and ultrastructural changes, and inflammatory cell infiltration of colon tissue were evaluated. Transcriptome and 16S rDNA sequencing were employed to illuminate the mechanism of FYC in the protection of UC mice. RESULTS: FYC significantly alleviates the pathological damage and the infiltration of inflammatory cells in colon tissue of dextran sulfate sodium induced UC mice, rescues shortened colon length, reduces DAI score, MPO content in serum, and pro-inflammatory factors including IL-1ß, IL-6, CCL11, MCP-1 and MIP-2, and increases anti-inflammatory factors such as IL-10. Transcriptomics revealed that Oncostatin M (OSM) and its receptor (OSMR) are the critical pathway for UC treatment by FYC. OSM and OSMR increased in UC mice compared to control mice, and decreased with FYC, which was verified via measurement of OSM and OSMR mRNA and protein levels. Furthermore, we observed that FYC modulates intestinal microbiome composition (e.g., the proportion of Barnesiella/Proteobacteria) by affecting the inflammatory factors. CONCLUSION: FYC exerts an effect on UC by inhibiting the OSM/OSMR pathway and regulating inflammatory factors to improve the intestinal flora.


Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Subunidad beta del Receptor de Oncostatina M/metabolismo , Oncostatina M/metabolismo , Animales , Antiinflamatorios no Esteroideos/farmacología , Cápsulas , Quimiocinas/sangre , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/microbiología , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Colon/ultraestructura , Citocinas/sangre , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Microbioma Gastrointestinal/genética , Masculino , Ratones Endogámicos C57BL , Oncostatina M/genética , Subunidad beta del Receptor de Oncostatina M/genética , Sustancias Protectoras/farmacología
11.
Food Chem ; 340: 128123, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33010645

RESUMEN

Six commercial red sorghum varieties (Tong Za 117, 141, 142 and 143, Chi Za 109 and 101) were investigated for their triacylglycerol (TAG) profiles, soluble and bound phenolics, and radical scavenging and anti-inflammatory activities. A total of 21 TAGs were identified in red sorghum oils for the first time. Total phenolic (TPC) and flavonoid contents (TFC) in the soluble or bound phenolic fractions differed among red sorghums. Significant correlation among TPC, TFC and DPPH radical scavenging activities was observed in both fractions. Except for caffeic acid, most of phenolic acids in red sorghums are in the bound form. Soluble 3-deoxyanthocyanidins contents (2.12-57.14 µg/g) were significantly higher than those of bound forms (0.01-0.18 µg/g) regardless of sorghum varieties and types of 3-deoxyanthocyanidins. Moreover, the stronger anti-inflammatory capacity of soluble phenolic fraction in Tong Za 117 correlated with its higher TPC, TFC and radical scavenging activity than those of its bound counterpart.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Depuradores de Radicales Libres/farmacología , Sorghum/química , Triglicéridos/análisis , Triglicéridos/farmacología , Animales , Antiinflamatorios no Esteroideos/química , Antioxidantes/química , Ácidos Cafeicos/análisis , Ácidos Cafeicos/química , Diterpenos/análisis , Flavonoides/análisis , Depuradores de Radicales Libres/química , Hidrólisis , Hidroxibenzoatos/análisis , Hidroxibenzoatos/química , Ratones , Fenoles , Extractos Vegetales/química , Aceites Vegetales/análisis , Aceites Vegetales/química , Células RAW 264.7
12.
Georgian Med News ; (306): 137-142, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33130661

RESUMEN

In humans and mammals, the homeostasis system is supported by many organs and systems, but hematopoietic remains one of the most important. A negative effect on the hematopoietic system is rejected by many factors, but the first place remains for drugs, which one in three are non-steroidal anti-inflammatory drugs (NSAIDs). The most popular among them remains the active substance "Diclofenac Sodium", which is part of many drugs. The purpose of the work is to study the action of the active substance Diclofenac sodium and its effect on the erythrocyte series of bone marrow cells of white laboratory mice in an experiment. The studies were conducted on white laboratory mice, males, 6 months old, 60 grams. The animals were divided into three groups, the first received 0.09 mg of Diclofenac sodium in the quadriceps of the thigh, the second - 0.18 mg and the third physiological solution for 96 hours. After observing all the rules of bioethics, the animals were slaughtered and the bone marrow was examined using pure immuno-magnetic separation techniques. During the study, it became known that in the first group the number of erythroblasts increased by 75%, while in the second group by 166.5%, due to the blocking of differentiation into more mature cells. The number of reticular cells decreased by 33.4%, while in the second group by 60%. A decrease in the erythrokaryocyte maturation index in the first group by 42.6% whereas in the second by 32.5%, primarily due to immature red blood cell precursors. In the first group, the leuko-erythrokaryoid ratio decreased by 9.5%, while in the second group by 12.3%. The number of megakaryocytes due to the predominant blockade of cyclooxygenase-2 increased in the first group by 266.6%, while in the second by 733.3%. It was found that the most favorable effect on red bone marrow cells has a dose of 0.09 mg, while 0.18 mg has a toxic effect and contributes to the development of cardiovascular complications.


Asunto(s)
Antiinflamatorios no Esteroideos , Diclofenaco , Animales , Antiinflamatorios no Esteroideos/farmacología , Células de la Médula Ósea , Humanos , Lactante , Masculino , Ratones
13.
Biomolecules ; 10(11)2020 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-33147723

RESUMEN

Plants have been used as drugs to treat human disease for centuries. Ursonic acid (UNA) is a naturally occurring pentacyclic triterpenoid extracted from certain medicinal herbs such as Ziziphus jujuba. Since the pharmacological effects and associated mechanisms of UNA are not well-known, in this work, we attempt to introduce the therapeutic potential of UNA with a comparison to ursolic acid (ULA), a well-known secondary metabolite, for beneficial effects. UNA has a keto group at the C-3 position, which may provide a critical difference for the varied biological activities between UNA and ULA. Several studies previously showed that UNA exerts pharmaceutical effects similar to, or stronger than, ULA, with UNA significantly decreasing the survival and proliferation of various types of cancer cells. UNA has potential to exert inhibitory effects in parasitic protozoa that cause several tropical diseases. UNA also exerts other potential effects, including antihyperglycemic, anti-inflammatory, antiviral, and antioxidant activities. Of note, a recent study highlighted the suppressive potential of UNA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular modifications of UNA may enhance bioavailability, which is crucial for in vivo and clinical studies. In conclusion, UNA has promising potential to be developed in anticancer and antiprotozoan pharmaceuticals. In-depth investigations may increase the possibility of UNA being developed as a novel reagent for chemotherapy.


Asunto(s)
Antivirales/farmacología , Triterpenos/farmacología , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Antiprotozoarios/química , Antiprotozoarios/farmacología , Antivirales/química , Betacoronavirus/efectos de los fármacos , Betacoronavirus/fisiología , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Plantas/química , Triterpenos/química , Triterpenos/metabolismo
14.
Arq. ciências saúde UNIPAR ; 24(3): 139-144, set-dez. 2020.
Artículo en Portugués | LILACS | ID: biblio-1129451

RESUMEN

O naproxeno, assim como outros anti-inflamatórios não esteroides (AINEs), está entre os medicamentos mais prescritos no mundo. O objetivo do presente estudo é analisar o efeito da ingestão de naproxeno em parâmetros neuromusculares e determinar seu efeito no dano muscular por meio do uso do marcador lactato. Metodologicamente, foi conduzido um estudo cruzado randomizado, duplo-cego e controlado por placebo em 11 homens treinados em resistência, que realizaram uma sessão de treinamento de força após ingerir 500 mg de naproxeno e outra sessão de treinamento após ingerir um placebo. Os participantes realizaram três séries de supino horizontal com uma carga de 90% da repetição máxima (1RM) até a falha concêntrica. As variáveis de resultado incluíram número de repetições, carga de trabalho e lactato. Os resultados mostraram que há uma correlação positiva e moderada entre as variáveis somatório de repetições e carga total e entre as variáveis lactato e carga total, no grupo naproxeno. No grupo placebo, a correlação positiva e moderada deu-se entre somatório de repetições e carga total. Na análise magnitude baseada nas interferências, as variáveis se mostraram possíveis para uma probabilidade positiva ou trivial e improvável para uma probabilidade negativa. Concluiu-se no presente estudo que o uso do naproxeno como recurso ergogênico no treinamento de força reduz a percepção de fadiga, mas não tem efeito direto no dano muscular, analisado a partir do marcador lactato, logo não interfere de maneira significativa nos parâmetros neuromusculares analisados.


Naproxen, as other non-steroidal anti-inflammatory drugs (NSAIDs), features among the most widely prescribed drugs in the world. The aim of this study is to analyze the effect of naproxen intake on neuromuscular parameters and determine its effect on muscle damage through the use of the lactate marker. In terms of methodology, a randomized, double-blind, placebo-controlled crossover study was conducted on 11 resistance-trained men who underwent a strength training session after taking 500 mg of naproxen and another training session after taking a placebo. The participants performed three sets of horizontal bench presses with a load of 90% maximum repetition (1RM) until concentric failure. Result variables included number of repetitions, workload and lactate. The results showed that there is a positive and moderate correlation between the sum of repetition and total load variables and between lactate and total load variables in the naproxen group. In the placebo group, a positive and moderate correlation was observed between sum of repetitions and total load. In the magnitude analysis, based on the interferences, the variables were shown to be possible for a positive or trivial probability and unlikely for a negative probability. It was concluded that the use of naproxen as an ergogenic resource in strength training reduces the perception of fatigue but has no direct effect on muscle damage when analyzed from the lactate marker, therefore it does not significantly interfere in the analyzed neuromuscular parameters.


Asunto(s)
Humanos , Masculino , Adulto , Antiinflamatorios no Esteroideos/farmacología , Naproxeno/farmacología , Fatiga Muscular/efectos de los fármacos , Fuerza Muscular/efectos de los fármacos , Fármacos Neuromusculares/farmacología , Supinación , Método Doble Ciego , Entrenamiento de Resistencia , Sustancias para Mejorar el Rendimiento/farmacología , Lactatos/sangre , Músculos/metabolismo
15.
Inflamm Res ; 69(12): 1257-1270, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33037469

RESUMEN

OBJECTIVE AND DESIGN: Methyl gallate (MG) is a prevalent polyphenol in the plant kingdom, which may be related to the effects of several medicinal plants. Although it is widely reported that polyphenols have therapeutic effects, there are few studies demonstrating that MG has anti-inflammatory action. This study aimed to investigate the molecular mechanism behind the anti-inflammatory activity of MG and its effect on hyperalgesia. METHODS: Swiss mice were pretreated orally with different doses of MG and subjected to i.pl. injection of zymosan to induce paw edema. RAW264.7 macrophages and BMDMs stimulated with different TLR agonists such as zymosan, LPS, or Pam3CSK4 were used to investigate the molecular mechanisms of MG RESULTS: MG inhibits zymosan-induced paw edema and hyperalgesia and modulates molecular pathways crucial for inflammation development. Pretreatment with MG inhibited cytokines production and NF-κB activity by RAW 264.7 cells stimulated with zymosan, Pam3CSK4 or LPS, but not with PMA. Moreover, pretreatment with MG decreased IκB degradation, nuclear translocation of NF-κBp65, c-jun and c-fos and ERK1/2, p38 and JNK phosphorylation. CONCLUSION: Thus, the results of this study demonstrate that MG has a promising anti-inflammatory effect and suggests an explanation of its mechanism of action through the inhibition of NF-κB signaling and the MAPK pathway.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Ácido Gálico/análogos & derivados , Inflamación/tratamiento farmacológico , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , FN-kappa B/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Receptores Toll-Like/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Citocinas/metabolismo , Edema/inducido químicamente , Edema/tratamiento farmacológico , Ácido Gálico/farmacología , Ácido Gálico/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Masculino , Ratones , Células RAW 264.7 , Zimosan
16.
Phytomedicine ; 79: 153328, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33007730

RESUMEN

BACKGROUND: Chaiqin chengqi decoction (CQCQD) is a Chinese herbal formula derived from dachengqi decoction. CQCQD has been used for the management of acute pancreatitis (AP) in the West China Hospital for more than 30 years. Although CQCQD has a well-established clinical efficacy, little is known about its bioactive ingredients, how they interact with different therapeutic targets and the pathways to produce anti-inflammatory effects. PURPOSE: Toll-like receptor 4 (TLR4) and the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated pro-inflammatory signaling pathways, play a central role in AP in determining the extent of pancreatic injury and systemic inflammation. In this study, we screened the bioactive ingredients using a pharmacological sub-network analysis based on the TLR4/NLRP3 signaling pathways followed by experimental validation. METHODS: The main CQCQD bioactive compounds were identified by UPLC-QTOF/MS. The TLR4/NLRP3 targets in AP for CQCQD active ingredients were confirmed through a pharmacological sub-network analysis. Mice received 7 intraperitoneal injections of cerulein (50 µg/kg; hourly) to induce AP (CER-AP), while oral gavage of CQCQD (5, 10, 15 and 20 g/kg; 3 doses, 2 hourly) was commenced at the 3rd injection of cerulein. Histopathology and biochemical indices were used for assessing AP severity, while polymerase chain reaction, Western blot and immunohistochemistry analyses were used to study the mechanisms. Identified active CQCQD compounds were further validated in freshly isolated mouse pancreatic acinar cells and cultured RAW264.7 macrophages. RESULTS: The main compounds from CQCQD belonged to flavonoids, iridoids, phenols, lignans, anthraquinones and corresponding glycosides. The sub-network analysis revealed that emodin, rhein, baicalin and chrysin were the compounds most relevant for directly regulating the TLR4/NLRP3-related proteins TLR4, RelA, NF-κB and TNF-α. In vivo, CQCQD attenuated the pancreatic injury and systemic inflammation of CER-AP and was associated with reduced expression of TLR4/NLRP3-related mRNAs and proteins. Emodin, rhein, baicalin and chrysin significantly diminished pancreatic acinar cell necrosis with varied effects on suppressing the expression of TLR4/NLRP3-related mRNAs. Emodin, rhein and chrysin also decreased nitric oxide production in macrophages and their combination had synergistic effects on alleviating cell death as well as expression of TLR4/NLRP3-related proteins. CONCLUSIONS: CQCQD attenuated the severity of AP at least in part by inhibiting the TLR4/NLRP3 pro-inflammatory pathways. Its active ingredients, emodin, baicalin, rhein and chrysin contributed to these beneficial effects.


Asunto(s)
Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Inflamasomas/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pancreatitis/tratamiento farmacológico , Células Acinares/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Ceruletida/toxicidad , Emodina/farmacología , Flavonoides/farmacología , Inflamasomas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Pancreatitis/inducido químicamente , Pancreatitis/metabolismo , Pancreatitis/patología , Células RAW 264.7 , Receptor Toll-Like 3/antagonistas & inhibidores
17.
Cardiol Rev ; 28(6): 303-307, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33017365

RESUMEN

Severe acute respiratory distress syndrome coronavirus 2 (COVID-19) is the cause of the current pandemic, which remains a tremendous cause of morbidity and mortality worldwide. Although there are numerous trials underway, there is currently no medication known to cure the infection. Nonsteroidal anti-inflammatory drugs (NSAIDs) are inexpensive, widely available medications with antiviral and anti-inflammatory properties and may have utility as an adjunct therapy to improve outcomes in patients with severe COVID-19 infection. A thorough PubMed literature review on the therapeutic use of NSAID was conducted to provide a comprehensive perspective of the role of NSAIDs in treating COVID-19. NSAIDs may be a useful adjunct therapy for patients with severe COVID-19 infection, but further investigation and clinical trials are necessary to ensure their safety and efficacy.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Humanos , Pandemias , Resultado del Tratamiento
18.
Phytomedicine ; 78: 153309, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32890914

RESUMEN

BACKGROUND: Combination drug therapy has become an effective strategy for inflammation control. The anti­inflammatory capacities of silibinin and thymol have each been investigated on its own, but little is known about the synergistic anti-inflammatory effects of these two compounds. PURPOSE: This study aims to investigate the synergistic anti-inflammatory effects of silibinin and thymol when administered in combination to lipopolysaccharide (LPS)-induced RAW264.7 cells. METHODS: RAW264.7 cells were pre-treated with silibinin and thymol individually or in combination for 2 h before LPS stimulation. Cell viability was detected by the MTT assay. Nitric oxide (NO) production was measured by Griess reagent. Reactive oxygen species (ROS) was evaluated by 2',7'-dichlorofluorescein-diacetate. ELISA was used to detect tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Western blot was performed to analyse the protein expression of LPS-induced RAW264.7 cells. RESULTS: We observed a synergistic anti-inflammatory effect of silibinin and thymol when administered in combination to LPS-induced RAW264.7 cells. Silibinin combined with thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) had more potent effects on the inhibition of NO, TNF-α, and IL-6 than those exerted by individual administration of these compounds in LPS-induced RAW264.7 cells. The combination of silibinin and thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) strongly inhibited ROS and cyclooxygenase-2 (COX-2). More importantly, the combination of silibinin and thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) was also successful in inhibiting nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) activities. Our results suggest that the synergistic anti-inflammatory effects of silibinin with thymol were associated with the inhibition of NF-κB and MAPK signalling pathways. CONCLUSION: The combination of silibinin and thymol (40 µM and 120 µM, respectively, with the molar ratio 1:3) could inhibit inflammation by suppressing NF-κB and MAPK signalling pathways in LPS-induced RAW264.7 cells.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , FN-kappa B/metabolismo , Silibina/farmacología , Timol/farmacología , Animales , Ciclooxigenasa 2/metabolismo , Sinergismo Farmacológico , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/toxicidad , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Óxido Nítrico/metabolismo , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
19.
Adv Exp Med Biol ; 1274: 29-54, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32894506

RESUMEN

Prostanoids (prostaglandins, prostacyclin and thromboxane) belong to the oxylipin family of biologically active lipids generated from arachidonic acid (AA). Protanoids control numerous physiological and pathological processes. Cyclooxygenase (COX) is a rate-limiting enzyme involved in the conversion of AA into prostanoids. There are two COX isozymes: the constitutive COX-1 and the inducible COX-2. COX-1 and COX-2 have similar structures, catalytic activities, and subcellular localizations but differ in patterns of expression and biological functions. Non-selective COX-1/2 or traditional, non-steroidal anti-inflammatory drugs (tNSAIDs) target both COX isoforms and are widely used to relieve pain, fever and inflammation. However, the use of NSAIDs is associated with various side effects, particularly in the gastrointestinal tract. NSAIDs selective for COX-2 inhibition (coxibs) were purposefully designed to spare gastrointestinal toxicity, but predisposed patients to increased cardiovascular risks. These health complications from NSAIDs prompted interest in the downstream effectors of the COX enzymes as novel drug targets. This chapter describes various safety issues with tNSAIDs and coxibs, and discusses the current development of novel classes of drugs targeting the prostanoid pathway, including nitrogen oxide- and hydrogen sulfide-releasing NSAIDs, inhibitors of prostanoid synthases, dual inhibitors, and prostanoid receptor agonists and antagonists.


Asunto(s)
Antagonistas de Prostaglandina/farmacología , Antagonistas de Prostaglandina/uso terapéutico , Prostaglandinas/metabolismo , Transducción de Señal/efectos de los fármacos , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Humanos , Prostaglandina-Endoperóxido Sintasas/metabolismo
20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(8): 673-679, 2020 Aug.
Artículo en Chino | MEDLINE | ID: mdl-32958122

RESUMEN

Objective To investigate the therapeutic effect and mechanism of paeoniflorin on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) mice. Methods C57BL/6 male mice were randomly divided into control group, model group, 600 mg/(kg.d) mesalazine treatment group, (12.5, 25, 50) mg/(kg.d) paeoniflorin treatment group, with 10 mice in each. All mice were treated with 30 g/L DSS for 5 days except the control group. Meanwhile, the mice in the other groups were orally administrated corresponding drugs for 10 days, while the mice in the control and model groups were given equivalent volumes of distilled water. Body mass, fecal characteristics and hematochezia of the mice were observed and recorded daily, and then disease activity index (DAI) was evaluated and calculated. Pathological changes in the colon were observed by HE staining. The levels of anti-flagellin antibody, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the serum were measured by ELISA. The expression levels of Toll-like receptor 5 (TLR5), myeloid differentiation factor 88 (MyD88) and nuclear factor kappa-Bp65 (NF-κBp65) in the colon tissues were evaluated by Western blot analysis and the activation of lymphocytes in mesenteric lymph node (MLN) was detected by flow cytometry. Results Compared with the control group, DAI scores in the model group were significantly raised, the colon length was significantly shortened, and the epithelium and intestinal gland disappeared. In addition, the serum levels of anti-flagellin antibody, IL-6, TNF-α and the protein levels of TLR5, MyD88, NF-κBp65 in the colon significantly increased, and the activation of T lymphocytes in MLN went up in the model group. All symptoms above were alleviated in the mesalazine and paeoniflorin groups compared with the model group. Conclusion Paeoniflorin can attenuate UC in mice by inhibiting the expression of flagellin and TLR5, and the activation of T cells.


Asunto(s)
Colitis Ulcerosa , Glucósidos , Activación de Linfocitos , Monoterpenos , Linfocitos T , Receptor Toll-Like 5 , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colon/efectos de los fármacos , Sulfato de Dextran/toxicidad , Glucósidos/farmacología , Glucósidos/uso terapéutico , Activación de Linfocitos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Monoterpenos/farmacología , Monoterpenos/uso terapéutico , Distribución Aleatoria , Linfocitos T/efectos de los fármacos , Receptor Toll-Like 5/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA