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1.
Int J Mol Med ; 47(4): 1, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33537817

RESUMEN

Inflammation is the most common cause of most acute and chronic debilitating diseases. Towards unveiling novel therapeutic options for patients with such complications, N­bromotaurine (TauNHBr) has emerged as a potential anti­inflammatory agent; however, its therapeutic efficacy is hindered due to its relatively poor stability. To address this challenge, the present study focused on examining the effects of a stable active bromine compound, named bromamine T (BAT). The present study examined the protective properties of BAT against lipopolysaccharide (LPS)­mediated inflammation in vitro, by using LPS­stimulated murine J774.A1 macrophages (Mφs), as well as in vivo, by using a murine LPS­mediated air­pouch model. Additionally, its efficacy was compared with that of taurine, a known potent anti­inflammatory molecule. In LPS­stimulated J774A.1 Mφs, BAT and taurine were very effective in reducing the secretion of pro­inflammatory mediators. The in vitro experiments indicated that LPS­mediated inflammation was attenuated due to the protective properties of BAT and of taurine, probably through the inhibition of phosphorylated p65 NF­κB subunit (Ser 536) nuclear translocation. The in vivo experiments also revealed that BAT and taurine inhibited LPS­mediated inflammation by reducing total cell/polymorphonuclear cell (PMN) infiltration in the air­pouch and by decreasing pouch wall thickness. The analysis of exudates obtained from pouches highlighted that the inhibitory effects of BAT and taurine on the secretion of pro­inflammatory cytokines were similar to those observed in vitro. Notably, the effect of BAT at the highest concentration tested was superior to that of taurine at the highest concentration. Taken together, the findings of the present study indicate that BAT prevents the LPS­induced inflammatory response both in vitro and in vivo.


Asunto(s)
Bromo/uso terapéutico , Inflamación/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Bromo/farmacología , Línea Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/patología , Mediadores de Inflamación/metabolismo , Lipopolisacáridos , Ratones Endogámicos C57BL , Fosforilación/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Sulfonamidas/farmacología , Taurina/farmacología , Factor de Transcripción ReIA/metabolismo , Transcripción Genética/efectos de los fármacos
2.
Nat Commun ; 12(1): 773, 2021 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-33536439

RESUMEN

Macrophages are plastic and, in response to different local stimuli, can polarize toward multi-dimensional spectrum of phenotypes, including the pro-inflammatory M1-like and the anti-inflammatory M2-like states. Using a high-throughput phenotypic screen in a library of ~4000 FDA-approved drugs, bioactive compounds and natural products, we find ~300 compounds that potently activate primary human macrophages toward either M1-like or M2-like state, of which ~30 are capable of reprogramming M1-like macrophages toward M2-like state and another ~20 for the reverse repolarization. Transcriptional analyses of macrophages treated with 34 non-redundant compounds identify both shared and unique targets and pathways through which the tested compounds modulate macrophage activation. One M1-activating compound, thiostrepton, is able to reprogram tumor-associated macrophages toward M1-like state in mice, and exhibit potent anti-tumor activity. Our compound-screening results thus help to provide a valuable resource not only for studying the macrophage biology but also for developing therapeutics through modulating macrophage activation.


Asunto(s)
Antiinflamatorios/farmacología , Productos Biológicos/farmacología , Ensayos Analíticos de Alto Rendimiento/métodos , Activación de Macrófagos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Animales , Antiinflamatorios/química , Productos Biológicos/química , Línea Celular Tumoral , Células Cultivadas , Expresión Génica/efectos de los fármacos , Ontología de Genes , Humanos , Macrófagos/clasificación , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Neoplasias Experimentales/prevención & control , Fenotipo , Células THP-1 , Tioestreptona/química , Tioestreptona/farmacología
3.
Biomed Res Int ; 2021: 6694572, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33521129

RESUMEN

Allanblackia floribunda has been used to treat an upset stomach in African traditional medicine, but its efficacy and safety have not been scientifically studied. The present research is aimed at assessing the antiulcer property of the seed extract of the plant to validate its traditional claim. Rats were pretreated with three doses of aqueous extract of A. floribunda (AFE) at 30, 100, and 300 mg/kg or omeprazole 10 mg/kg for 1 hr before the acute gastric ulcer was induced by oral administration of 5 mL/kg of 98% ethanol. The animals were sacrificed under anesthesia, and the stomach and blood were collected. The gross histology of the stomach, percentage protection conferred by the treatment, gastric pH, and serum TNF-α and INF-γ were assessed as well as the expression of Ki67 antigens. The antioxidant properties as well as the acute toxicity profile of the plant extract were also assessed. The results show that A. floribunda conferred significant protection on the rats against gastric ulceration with % protection of 46.15, 57.69, and 65.38 for AFE 30, 100, and 300 mg/kg, respectively, as well as 69.23% for omeprazole 10 mg/kg. The plant extract caused marked reductions in gastric pH, TNF-α, and INF-γ with statistical significance (p < 0.001) for AFE 300 mg/kg and omeprazole 10 mg/kg. Also, the plant showed good antioxidant activity comparable to gallic acid. Furthermore, the plant extract modulated the expression of Ki67 antigens. All animals survived the 14-day delayed toxicity test with no significant differences in physical, hematological, and biochemical parameters between rats orally administered with supratherapeutic doses of AFE (5000 mg/kg) or normal saline. The study established that the gastroprotective effect of the seed extract of A. floribunda is attributable to its antisecretory, antioxidant, and anti-inflammatory properties. Additionally, the plant was found to promote ulcer healing via the modulation of the expression Ki67 and was safe at supratherapeutic doses.


Asunto(s)
Clusiaceae/química , Etanol/toxicidad , Interferón gamma/metabolismo , Antígeno Ki-67/metabolismo , Semillas/química , Úlcera Gástrica/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Compuestos de Bifenilo/química , Quelantes/farmacología , Modelos Animales de Enfermedad , Depuradores de Radicales Libres , Concentración 50 Inhibidora , Masculino , Óxido Nítrico/metabolismo , Fitoterapia , Picratos/química , Ratas , Ratas Sprague-Dawley , Úlcera Gástrica/inducido químicamente
4.
Int J Nanomedicine ; 16: 591-607, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33531803

RESUMEN

Purpose: The aim of the present study was to develop deflazacort (DFZ) ultra-elastic nanovesicles (UENVs) loaded gel for topical administration to evade gastrointestinal adverse impacts accompanying DFZ oral therapy. Methods: UENVs were elaborated according to D-optimal mixture design employing different edge activators as Span-60, Tween-85 and sodium cholate which were incorporated into the nanovesicles to improve the deformability of vesicles bilayer. DFZ-UENVs were formulated by thin-film hydration technique followed by characterization for different parameters including entrapment efficiency (%EE), particle size, in vitro release and ex vivo permeation studies. The composition of the optimized DFZ-UENV formulation was found to be DFZ (10 mg), Span-60 (30 mg), Tween-85 (30 mg), sodium cholate (3.93 mg), L-α phosphatidylcholine (60 mg) and cholesterol (30 mg). The optimum formulation was incorporated into hydrogel base then characterized in terms of physical parameters, in vitro drug release, ex vivo permeation study and pharmacodynamics evaluation. Finally, pharmacokinetic study in rabbits was performed via transdermal application of UENVs gel in comparison to oral drug. Results: The optimum UENVs formulation exhibited %EE of 74.77±1.33, vesicle diameter of 219.64±2.52 nm, 68.88±1.64% of DFZ released after 12 h and zeta potential of -55.57±1.04 mV. The current work divulged successful augmentation of the bioavailability of DFZ optimum formulation by about 1.37-fold and drug release retardation compared to oral drug tablets besides significant depression of edema, cellular inflammation and capillary congestion in carrageenan-induced rat paw edema model. Conclusion: The transdermal DFZ-UENVs can achieve boosted bioavailability and may be suggested as an auspicious non-invasive alternative platform for oral route.


Asunto(s)
Antiinflamatorios/farmacología , Sistemas de Liberación de Medicamentos , Elasticidad , Nanopartículas/química , Pregnenodionas/farmacología , Administración Cutánea , Administración Oral , Animales , Disponibilidad Biológica , Liberación de Fármacos , Edema/tratamiento farmacológico , Hidrogeles/química , Masculino , Nanopartículas/ultraestructura , Tamaño de la Partícula , Pregnenodionas/farmacocinética , Conejos , Ratas Wistar , Absorción Cutánea/efectos de los fármacos , Electricidad Estática , Comprimidos
5.
PLoS Negl Trop Dis ; 15(1): e0008895, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33395417

RESUMEN

A wide variety of symptoms is associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and these symptoms can overlap with other conditions and diseases. Knowing the distribution of symptoms across diseases and individuals can support clinical actions on timelines shorter than those for drug and vaccine development. Here, we focus on zinc deficiency symptoms, symptom overlap with other conditions, as well as zinc effects on immune health and mechanistic zinc deficiency risk groups. There are well-studied beneficial effects of zinc on the immune system including a decreased susceptibility to and improved clinical outcomes for infectious pathogens including multiple viruses. Zinc is also an anti-inflammatory and anti-oxidative stress agent, relevant to some severe Coronavirus Disease 2019 (COVID-19) symptoms. Unfortunately, zinc deficiency is common worldwide and not exclusive to the developing world. Lifestyle choices and preexisting conditions alone can result in zinc deficiency, and we compile zinc risk groups based on a review of the literature. It is also important to distinguish chronic zinc deficiency from deficiency acquired upon viral infection and immune response and their different supplementation strategies. Zinc is being considered as prophylactic or adjunct therapy for COVID-19, with 12 clinical trials underway, highlighting the relevance of this trace element for global pandemics. Using the example of zinc, we show that there is a critical need for a deeper understanding of essential trace elements in human health, and the resulting deficiency symptoms and their overlap with other conditions. This knowledge will directly support human immune health for decreasing susceptibility, shortening illness duration, and preventing progression to severe cases in the current and future pandemics.


Asunto(s)
/tratamiento farmacológico , Zinc/administración & dosificación , Zinc/deficiencia , Antiinflamatorios/farmacología , /virología , Humanos , Sistema Inmunológico/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/inmunología , Pandemias , Factores de Riesgo , /aislamiento & purificación
6.
Acta Cir Bras ; 35(12): e351205, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33503218

RESUMEN

PURPOSE: In laparoscopic incisional hernia repair, meshes with a tissue-separating barrier are positioned intraperitoneally. Despite this property, the close contact between mesh and viscera involves a risk of adhesion formation. Some natural products, such as red propolis (RP), could reduce these adhesions owing to their anti-inflammatory properties. This study aimed to compare two different intraperitoneal meshes with respect to their characteristics of adhesion formation, histological findings and evaluate the role of RP in the development of these adhesions. METHODS: 40 Wistar rats received placement of two different meshes (Symbotex and Dynamesh IPOM) on peritoneum. The animals were divided into two groups: control group (mesh) and treatment group (mesh and RP). After 7 and 14 days, 20 animals of each group underwent midline laparotomy to determine the adhesions and histological characteristics. RESULTS: Out of the 40 animals, there were two deaths in the test group and two in the control group. All animals in both groups developed adherence to the mesh. At postoperative day (POD) 7, two Symbotex meshes presented firm adhesions and at POD 14, two Dynamesh meshes had firm adhesions as well. The comparison between the meshes under the effect of RP in relation to the control group showed no statistical difference. CONCLUSIONS: Both meshes showed intraperitoneal adhesions in all evaluated samples with similar results on the characteristics of adhesions. RP showed no effect on the incidence or gradation of intraperitoneal adhesions with the mesh.


Asunto(s)
Productos Biológicos , Hernia Ventral , Animales , Antiinflamatorios/farmacología , Polipropilenos , Ratas , Ratas Wistar , Mallas Quirúrgicas/efectos adversos , Adherencias Tisulares/prevención & control
7.
Sci Rep ; 11(1): 1462, 2021 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-33446817

RESUMEN

Cannabis sativa is widely used for medical purposes and has anti-inflammatory activity. This study intended to examine the anti-inflammatory activity of cannabis on immune response markers associated with coronavirus disease 2019 (COVID-19) inflammation. An extract fraction from C. sativa Arbel strain (FCBD) substantially reduced (dose dependently) interleukin (IL)-6 and -8 levels in an alveolar epithelial (A549) cell line. FCBD contained cannabidiol (CBD), cannabigerol (CBG) and tetrahydrocannabivarin (THCV), and multiple terpenes. Treatments with FCBD and a FCBD formulation using phytocannabinoid standards (FCBD:std) reduced IL-6, IL-8, C-C Motif Chemokine Ligands (CCLs) 2 and 7, and angiotensin I converting enzyme 2 (ACE2) expression in the A549 cell line. Treatment with FCBD induced macrophage (differentiated KG1 cell line) polarization and phagocytosis in vitro, and increased CD36 and type II receptor for the Fc region of IgG (FcγRII) expression. FCBD treatment also substantially increased IL-6 and IL-8 expression in macrophages. FCBD:std, while maintaining anti-inflammatory activity in alveolar epithelial cells, led to reduced phagocytosis and pro-inflammatory IL secretion in macrophages in comparison to FCBD. The phytocannabinoid formulation may show superior activity versus the cannabis-derived fraction for reduction of lung inflammation, yet there is a need of caution proposing cannabis as treatment for COVID-19.


Asunto(s)
Antiinflamatorios/farmacología , Cannabinoides/farmacología , Cannabis/química , Células Epiteliales/inmunología , Macrófagos/inmunología , Extractos Vegetales/farmacología , /inmunología , Células A549 , Antiinflamatorios/química , /patología , Cannabinoides/química , Citocinas/inmunología , Células Epiteliales/patología , Células Epiteliales/virología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/inmunología , Humanos , Macrófagos/patología , Macrófagos/virología , Extractos Vegetales/química , Receptores de IgG/inmunología
8.
Medicine (Baltimore) ; 100(2): e24122, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33466183

RESUMEN

OBJECTIVE: To assess the impact of intraoperative intravenous dexamethasone on the reduction of postoperative morbidity in children undergoing adenotonsillectomy. METHODS: A double blind randomized controlled trial conducted among children undergoing adenotonsillectomy at a tertiary hospital in Korea from November 2018 to June 2019. Children were randomly assigned to receive dexamethasone (0.5 mg/kg, maximum dose 24 mg) or placebo intravenously after induction of anesthesia. The primary endpoint was the reduction of postoperative pain and postoperative nausea and vomiting (PONV); secondary endpoints were adverse effects like postoperative hemorrhage. RESULTS: The study included 105 children, and 67 were male. Their mean age was 6.2 ±â€Š2.1 years. There was no significant difference between the groups in terms of demographic data or the operation time. The pain scores of the dexamethasone group were lower than those of the control group, but no significant difference was found (all P > .05). The average pain visual analog scale (VAS) during the study period (day 0-7) was 3.67 ±â€Š1.59 and 4.40 ±â€Š2.01 in the dexamethasone group and control group, respectively (P-value = .107). When we compared early pain VAS (day 0-2) and late pain VAS (day 5-7), the dexamethasone group showed significantly lower early mean VAS compared to the control group (4.55 ±â€Š1.78 vs 5.40 ±â€Š2.05, P-value = .046). The mean VAS for PONV was significantly lower in the dexamethasone group than in the control group (1.89 ±â€Š2.22 vs 3.00 ±â€Š2.37, P value = .044). CONCLUSION: In children undergoing adenotonsillectomy, dexamethasone decreased the early postoperative pain and PONV without increasing postoperative hemorrhage.


Asunto(s)
Adenoidectomía/efectos adversos , Dexametasona/farmacología , Dolor Postoperatorio/tratamiento farmacológico , Náusea y Vómito Posoperatorios/tratamiento farmacológico , Tonsilectomía/efectos adversos , Adenoidectomía/métodos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Niño , Preescolar , Dexametasona/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Masculino , Dolor Postoperatorio/etiología , Pediatría/métodos , Náusea y Vómito Posoperatorios/etiología , República de Corea , Tonsilectomía/métodos , Escala Visual Analógica
9.
Theranostics ; 11(1): 316-329, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33391477

RESUMEN

Severe coronavirus disease 2019 (COVID-19) is characterized by systemic hyper-inflammation, acute respiratory distress syndrome, and multiple organ failure. Cytokine storm refers to a set of clinical conditions caused by excessive immune reactions and has been recognized as a leading cause of severe COVID-19. While comparisons have been made between COVID-19 cytokine storm and other kinds of cytokine storm such as hemophagocytic lymphohistiocytosis and cytokine release syndrome, the pathogenesis of cytokine storm has not been clearly elucidated yet. Recent studies have shown that impaired response of type-1 IFNs in early stage of COVID-19 infection played a major role in the development of cytokine storm, and various cytokines such as IL-6 and IL-1 were involved in severe COVID-19. Furthermore, many clinical evidences have indicated the importance of anti-inflammatory therapy in severe COVID-19. Several approaches are currently being used to treat the observed cytokine storm associated with COVID-19, and expectations are especially high for new cytokine-targeted therapies, such as tocilizumab, anakinra, and baricitinib. Although a number of studies have been conducted on anti-inflammatory treatments for severe COVID-19, no specific recommendations have been made on which drugs should be used for which patients and when. In this review, we provide an overview of cytokine storm in COVID-19 and treatments currently being used to address it. In addition, we discuss the potential therapeutic role of extracorporeal cytokine removal to treat the cytokine storm associated with COVID-19.


Asunto(s)
Antiinflamatorios/uso terapéutico , Síndrome de Liberación de Citoquinas/inmunología , Citocinas/metabolismo , Inmunosupresores/uso terapéutico , Antiinflamatorios/farmacología , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Azetidinas/farmacología , Azetidinas/uso terapéutico , /inmunología , Ensayos Clínicos como Asunto , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Citocinas/antagonistas & inhibidores , Citocinas/inmunología , Humanos , Inmunosupresores/farmacología , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Quinasas Janus/antagonistas & inhibidores , Quinasas Janus/metabolismo , Purinas/farmacología , Purinas/uso terapéutico , Pirazoles/farmacología , Pirazoles/uso terapéutico , Factores de Transcripción STAT/antagonistas & inhibidores , Factores de Transcripción STAT/metabolismo , Índice de Severidad de la Enfermedad , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Resultado del Tratamiento
10.
J Med Chem ; 64(1): 768-781, 2021 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-33440945

RESUMEN

Berberine (BBR), a traditional Chinese medicine, has therapeutic effects on a variety of inflammation-related diseases, but its direct proteomic targets remain unknown. Using activity-based protein profiling, we first demonstrated that BBR directly targets the NEK7 protein via the hydrogen bond between the 2,3-methylenedioxy and 121-arginine (R121) residues. The fact that R121 is located precisely within the key domain involved in the NEK7-NLRP3 interaction allows BBR to specifically block the NEK7-NLRP3 interaction and successively inhibit IL-1ß release, independent of the NF-κB and TLR4 signaling pathways. Moreover, BBR displays in vivo anti-inflammatory efficacy in a NEK7-dependent manner. Therefore, we consider NEK7 to be a key target of BBR in the treatment of NLRP3-related inflammatory diseases, and the development of novel NEK7-NLRP3 interaction inhibitors might be easily achieved using NEK7 as a target.


Asunto(s)
Antiinflamatorios/química , Berberina/química , Quinasas Relacionadas con NIMA/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/farmacología , Berberina/metabolismo , Berberina/farmacología , Sitios de Unión , Humanos , Enlace de Hidrógeno , Interleucina-1beta/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Monocitos/citología , Monocitos/efectos de los fármacos , Monocitos/metabolismo , FN-kappa B/metabolismo , Quinasas Relacionadas con NIMA/antagonistas & inhibidores , Quinasas Relacionadas con NIMA/genética , Proteína con Dominio Pirina 3 de la Familia NLR/química , Dominios y Motivos de Interacción de Proteínas/efectos de los fármacos , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Transducción de Señal/efectos de los fármacos , Relación Estructura-Actividad
11.
Aging (Albany NY) ; 13(2): 1571-1590, 2021 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-33465050

RESUMEN

The main aspects of severe COVID-19 disease pathogenesis include hyper-induction of proinflammatory cytokines, also known as 'cytokine storm', that precedes acute respiratory distress syndrome (ARDS) and often leads to death. COVID-19 patients often suffer from lung fibrosis, a serious and untreatable condition. There remains no effective treatment for these complications. Out of all cytokines, TNFα and IL-6 play crucial roles in cytokine storm pathogenesis and are likely responsible for the escalation in disease severity. These cytokines also partake in the molecular pathogenesis of fibrosis. Therefore, new approaches are urgently needed, that can efficiently and swiftly downregulate TNFα, IL-6, and the inflammatory cytokine cascade, in order to curb inflammation and prevent fibrosis, and lead to disease remission. Cannabis sativa has been proposed to modulate gene expression and inflammation and is under investigation for several potential therapeutic applications against autoinflammatory diseases and cancer. Here, we hypothesized that the extracts of novel C. sativa cultivars may be used to downregulate the expression of pro-inflammatory cytokines and pathways involved in inflammation and fibrosis. Initially, to analyze the anti-inflammatory effects of novel C. sativa cultivars, we used a well-established full thickness human 3D skin artificial EpiDermFTTM tissue model, whereby tissues were exposed to UV to induce inflammation and then treated with extracts of seven new cannabis cultivars. We noted that out of seven studied extracts of novel C. sativa cultivars, three (#4, #8 and #14) were the most effective, causing profound and concerted down-regulation of COX2, TNFα, IL-6, CCL2, and other cytokines and pathways related to inflammation and fibrosis. These data were further confirmed in the WI-38 lung fibroblast cell line model. Most importantly, one of the tested extracts had no effect at all, and one exerted effect that may be deleterious, signifying that careful cannabis cultivar selection must be based on thorough pre-clinical studies. The observed pronounced inhibition of TNFα and IL-6 is the most important finding, because these molecules are currently considered to be the main targets in COVID-19 cytokine storm and ARDS pathogenesis. Novel anti-TNFα and anti-IL-6 cannabis extracts can be useful additions to the current anti-inflammatory regimens to treat COVID-19, as well as various rheumatological diseases and conditions, and 'inflammaging' - the inflammatory underpinning of aging and frailty.


Asunto(s)
Cannabis , Síndrome de Liberación de Citoquinas , Interleucina-6/antagonistas & inhibidores , Extractos Vegetales/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Antiinflamatorios/farmacología , Cannabinoides/farmacología , Línea Celular , Fibroblastos/efectos de los fármacos , Humanos , Inflamación/virología , Piel/efectos de los fármacos , Técnicas de Cultivo de Tejidos
12.
Mar Drugs ; 19(2)2021 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-33513822

RESUMEN

Inorganic polyphosphate (polyP) is a widely distributed polymer found from bacteria to animals, including marine species. This polymer exhibits morphogenetic as well as antiviral activity and releases metabolic energy after enzymatic hydrolysis also in human cells. In the pathogenesis of the coronavirus disease 2019 (COVID-19), the platelets are at the frontline of this syndrome. Platelets release a set of molecules, among them polyP. In addition, the production of airway mucus, the first line of body defense, is impaired in those patients. Therefore, in this study, amorphous nanoparticles of the magnesium salt of polyP (Mg-polyP-NP), matching the size of the coronavirus SARS-CoV-2, were prepared and loaded with the secondary plant metabolite quercetin or with dexamethasone to study their effects on the respiratory epithelium using human alveolar basal epithelial A549 cells as a model. The results revealed that both compounds embedded into the polyP nanoparticles significantly increased the steady-state-expression of the MUC5AC gene. This mucin species is the major mucus glycoprotein present in the secreted gel-forming mucus. The level of gene expression caused by quercetin or with dexamethasone, if caged into polyP NP, is significantly higher compared to the individual drugs alone. Both quercetin and dexamethasone did not impair the growth-supporting effect of polyP on A549 cells even at concentrations of quercetin which are cytotoxic for the cells. A possible mechanism of the effects of the two drugs together with polyP on mucin expression is proposed based on the scavenging of free oxygen species and the generation of ADP/ATP from the polyP, which is needed for the organization of the protective mucin-based mucus layer.


Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Dexametasona/farmacología , Mucina 5AC/biosíntesis , Mucina 5AC/efectos de los fármacos , Quercetina/farmacología , Células A549 , Antiinflamatorios/química , Antioxidantes/química , Dexametasona/química , Depuradores de Radicales Libres/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Magnesio/química , Mucina 5AC/genética , Mucinas/biosíntesis , Mucinas/química , Nanopartículas , Tamaño de la Partícula , Plantas/química , Polifosfatos/química , Quercetina/química , Especies Reactivas de Oxígeno
13.
Immunopharmacol Immunotoxicol ; 43(1): 37-50, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33406943

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19) has infected millions of individuals and has claimed hundreds of thousands of human lives worldwide. Patients with underlying cardiovascular conditions are at high risk for SARS-CoV-2 infection, and COVID-19 patients have high incidence of cardiovascular complications such as acute cardiac injury, arrhythmias, heart failure, and thromboembolism. The disease has no approved proven effective therapy and hence repurposing of existing approved drugs has been considered as the fastest treatment approach. Statins have been shown to exhibit lipid lowering dependent and independent cardiovascular protective effects as well as favorable effects in various other pathophysiological states. These beneficial properties of statins are a result of their multiple pleotropic effects that include, anti-inflammatory, immunomodulatory, antithrombotic and antimicrobial properties. In this review, we provide a comprehensive description of the mechanisms of the pleotropic effects of statins, the relevant pre-clinical and clinical data pertinent to their role in infections and acute lung injury, the possible cardiovascular benefits of statins in COVID-19, and the implications of the therapeutic potential of statins in COVID-19 disease. We conclude with the rationale for conducting randomized controlled trials of statins in COVID-19 disease.


Asunto(s)
/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/etiología , Antiinflamatorios/farmacología , Antivirales/farmacología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Neumonía/tratamiento farmacológico , Neumonía/etiología
14.
Med Hypotheses ; 146: 110415, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33422363

RESUMEN

COVID-19 is characterized by two major clinical phases, the SARS-CoV-2 infection of target cells and tissues, and a deep inflammatory state, known as "cytokine storm", caused by activation of pro-inflammatory genes, such as NF-kB, STAT-3, IL-6, IL-8, IL-1ß. Among possible anti-inflammatory agents, the "microRNA targeting" should be carefully considered, since it is well known that microRNAs are deeply involved in the expression of cytokines, chemokines and growth factors. The working general hypothesis is that targeting the microRNA network might be important for the development of therapeutic approaches to counteract the COVID-19 induction of inflammatory response. This hypothesis is based on several publications demonstrating the use of miRNA mimics for inhibitory effects on the production of proteins characterizing the COVID-19 "cytokine storm".


Asunto(s)
/terapia , Síndrome de Liberación de Citoquinas/terapia , MicroARNs/genética , Modelos Biológicos , Regiones no Traducidas 3'/genética , Antiinflamatorios/farmacología , /inmunología , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/inmunología , Humanos , Inflamación/genética , Inflamación/inmunología , Inflamación/terapia , MicroARNs/uso terapéutico , Imitación Molecular , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/genética
15.
Med Hypotheses ; 146: 110473, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33385879

RESUMEN

Severe forms of the Coronavirus disease 2019 (COVID-19) are characterized by an enhanced inflammatory syndrome called "cytokine storm" that produces an aberrant release of high amounts of cytokines, chemokines, and other proinflammatory mediators. The pathogenetic role of the "cytokine storm" has been confirmed by the efficacy of immunosuppressive drugs such as corticosteroids along with antiviral drugs in the treatment of the severe forms of this disease. Phenylmethimazole (C10) is a derivative of methimazole with anti-inflammatory properties. Studies performed both in vitro and in vivo have shown that C10 is able to block the production of multiple cytokines, chemokines, and other proinflammatory molecules involved in the pathogenesis of inflammation. Particularly, C10 is effective in reducing the increased secretion of cytokines in animal models of endotoxic shock. We hypothesize that these effects are not limited to the endotoxic shock, but can also be applied to any disease characterized by the presence of a "cytokine storm". Therefore, C10 may be a potential drug to be used alternatively or in association with the corticosteroids or other immunosuppressive agents in the severe forms of COVID-19 as well as other viral diseases that induce a "cytokine storm". Preclinical and clinical studies have to be performed to confirm this hypothesis.


Asunto(s)
/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Metimazol/análogos & derivados , Tionas/farmacología , Animales , Antiinflamatorios/farmacología , Antivirales/farmacología , Síndrome de Liberación de Citoquinas/inmunología , Citocinas/antagonistas & inhibidores , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Humanos , Metimazol/farmacología , Ratones , Pandemias , Choque Séptico/tratamiento farmacológico , Choque Séptico/inmunología , Investigación en Medicina Traslacional
16.
Med Hypotheses ; 146: 110468, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33385878

RESUMEN

Currently, no single medication has been approved for the management of coronavirus disease-2019 (COVID-19) caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, drug repositioningby investigating the use of existing drugs for management of COVID-19 patients is considered a desperate need. Tramadol is a commonly prescribed analgesic drug for treatment of moderate to severe pain with less potential for dependence and respiratory depression. Multiple evidence support that tramadol is a promising drug for treatment of COVID-19 patients. Herein, we discuss the possible beneficial effects of using tramadol against SARS-CoV-2 infection and their underlying mechanism of action. The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). Besides, tramadol activates natural killer (NK) and T-cells and enhances IL-2 secretion, which produce immune-enhancing effect against SARS-CoV-2. Recent studies confirmed that COVID-19 patients with acute respiratory failure showed increased fibrin formation and polymerization that may lead to thrombosis. Tramadol owing to its hypocoagulable effect may protect against venous thromboembolism in these patients. Moreover, tramadol can exert a cardioprotective effect via decreasing lactate dehydrogenase (LDH) level which is elevated in most of patients with COVID-19. Furthermore, the severity and mortality of COVID-19 have been correlated with old age patients, which may be due to the lack of antioxidant mechanisms and increased oxidative damage. Tramadol could protect COVID-19 patient from disease complications by increases the antioxidant enzymes superoxide dismutase and glutathione peroxidase while diminished malondialdehyde. More interestingly, tramadol as an effective analgesic and antitussive may have a beneficial effect on COVID-19 patients suffering from cough, headache, ache, and pain. The tramadol anti-psychotic effect may also protect against psychiatric disorders associated with SARS-CoV-2 infection. Moreover, tramadol has bactericidal activity against a wide range of pathogens including Pseudomonas aeruginosa which is common in severe COVID-19 patients leading to pneumonia with worse clinical outcomes. Therefore, we hypothesize that tramadol might be a promising adjuvant therapeutic option against SARS-CoV-2 infection. Based on that, tramadol should be considered as adjuvant therapy for COVID-19 clinical trials.


Asunto(s)
/tratamiento farmacológico , Tramadol/farmacología , Analgésicos Opioides/farmacología , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Antidepresivos/farmacología , Antioxidantes/farmacología , /fisiopatología , Reposicionamiento de Medicamentos , Humanos , Factores Inmunológicos/farmacología , Modelos Biológicos , Pandemias
17.
J Ethnopharmacol ; 266: 113408, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-32979409

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The preparations of Phlomis aerial parts are used traditionally in Anatolia for wound healing and in inflammatory disorders. METHODS: For the identification of the active fraction, the air dried aerial parts of Phlomis rigida Labill. were extracted by methanol and fractionated successively by n-hexane, dichloromethane and ethyl acetate, respectively. The phenolic constituents were characterized by the Folin-Ciocaltheu method; the antioxidant activity was performed by ABTS and DPPH radical scavenging assays. In vitro anti-inflammatory activity was evaluated by LOX enzyme inhibition, spectrophotometrically as well as cell cultures. The wound healing properties of P. rigida extract gels were studied via in vitro cell culture methods and in vivo by excisional wound model using Balb-c mice. The P. rigida extract was analyzed and characterized by GC-FID, GC-MS, and LC-MS. RESULTS: The P. rigida methanol extract showed moderate LOX inhibitory at IC50 = 19.5 ± 2.8 µg/mL whereas the antioxidant activity was by DPPH• IC50 = 0.89 mg/mL, and by ABTS• IC50 = 0.99 mg/mL, respectively. In addition, a remarkable P. rigida extracts anti-inflammatory activity was observed in the cell culture assay, which was then confirmed by the in vitro wound healing activity applied at 0.125-0.5 mg/mL concentrations, resulting in a dose-dependent increase in wound closure at the final stage. The P. rigida gel formulation was prepared to evaluate the extract in vivo, whereas the experimental results of the new gel formulation supported the findings of the in vitro wound healing activity. CONCLUSION: The findings of this in vitro and in vivo study suggest that the wound healing and anti-inflammatory properties provide a scientific evidence of the ethnopharmacological application of Phlomis species.


Asunto(s)
Analgésicos/farmacología , Antiinflamatorios/farmacología , Phlomis/química , Extractos Vegetales/farmacología , Analgésicos/administración & dosificación , Analgésicos/aislamiento & purificación , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Depuradores de Radicales Libres/administración & dosificación , Depuradores de Radicales Libres/aislamiento & purificación , Depuradores de Radicales Libres/farmacología , Inflamación/tratamiento farmacológico , Inflamación/patología , Concentración 50 Inhibidora , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/administración & dosificación , Células RAW 264.7 , Cicatrización de Heridas/efectos de los fármacos
18.
J Ethnopharmacol ; 266: 113406, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-32979410

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Eryngium carlinae F. Delaroche (Apiaceae) is an herb used in folk medicine as a diuretic, analgesic, and anti-inflammatory agent. AIM OF THE STUDY: This work assessed the diuretic, antinociceptive, and anti-inflammatory actions of an ethanol extract from the leaves and stems of Eryngium carlinae (ECE). These ethnomedicinal properties of ECE were scientifically validated using in vitro and in vivo assays. MATERIALS AND METHODS: The antinociceptive and diuretic actions of ECE (10-200 mg/kg p.o.) were assessed with the acetic acid-induced writhing test and by using metabolic cages to house mice, respectively. The in vitro anti-inflammatory actions of ECE (1-500 µg/ml) were evaluated using LPS-stimulated primary murine macrophages, and the in vivo anti-inflammatory actions were assessed using the TPA-induced ear edema test (2 mg/ear) and carrageenan-induced paw edema test (50-200 mg/kg p.o.). The production of inflammatory mediators was estimated using in vitro and in vivo assays. RESULTS: ECE lacked antinociceptive and diuretic effects. ECE increased the production of IL-10 in LPS-stimulated macrophages (EC50 = 37.8 pg/ml) and the carrageenan-induced paw edema test (ED50 = 82.6 mg/kg). ECE showed similar in vivo anti-inflammatory actions compared to those observed with indomethacin. CONCLUSION: ECE exerts in vitro and in vivo anti-inflammatory effects by increasing the release of IL-10.


Asunto(s)
Antiinflamatorios/farmacología , Eryngium/química , Inflamación/tratamiento farmacológico , Extractos Vegetales/farmacología , Analgésicos/farmacología , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Carragenina , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Edema/tratamiento farmacológico , Etanol/química , Indometacina/farmacología , Inflamación/patología , Mediadores de Inflamación/metabolismo , Interleucina-10/metabolismo , Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Componentes Aéreos de las Plantas , Extractos Vegetales/administración & dosificación
19.
J Ethnopharmacol ; 266: 113405, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-32979412

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Penyanling is made up of Smilacis Glabrae Rhizoma (SG, from Smilar glabra Roxb.), Angelicae Sinensis Radix (AS, from Angelica sinensis (Oliv.) Diels), Salviae Miltiorrhizae Radix et Rhizoma (SM, from Salvia miltiorrhiza Bunge), Sargentodoxae Caulis (SC, from Sargentodoxa cuneata (Oliv.) Rehd.et Wils.), Linderae Radix (LR, from Lindera aggregata (Sims) Kosterm.), Paeoniae Radix Rubra (PR, from Paeonia lactiflora Pall.), Sparganii Rhizoma (SR, from Sparganium stoloniferum (Graebn.) Buch.-Ham.), Corydalis Rhizoma (CoR, from Corydalis yanhusuo W. T. Wang), Cyperi Rhizoma (CyR, from Cyperus rotundus Linn.), Glycyrrhizae Radix et Rhizoma (GR, from Glycyrrhiza uralensis Fisch.), and Patrinia Scabiosaefolia (PS, from Patrinia scabiosaefolia Fisch. ex Trev.) recorded in Chinese Pharmacopoeia. It has been used on pelvic inflammatory disease (PID) for more than twenty years. AIM OF THE STUDY: This study was carried out to illustrate its pharmacological action and clarify its substantial composition. MATERIALS AND METHODS: The anti-inflammatory effects of Penyanling were studied on a PID rat model and a lipopolysaccharides (LPS)-stimulated THP-1 cell line. Histological changes and levels of inflammatory factors in the uterine tube of the PID rat were examined. Levels of nuclear factor-kappa B (NF-κB) in the nuclear of THP-1 cells and NF-κB, IκB-α, and FPR2 in the cytoplasm were tested by Western blot analysis. Substances within Penyanling were scanned with liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-Q-TOF-MS). The contents of total flavonoids, phenolics, and saponins were quantified. RESULTS: The anti-inflammatory effects of Penyanling were observed on PID rats, such as suppressing the infiltrations of lymphocytes and neutrophils in the uterine tube, decreasing the release of interleukin (IL)-1ß, IL-6, IL-8, and monocyte chemotactic protein (MCP)-1, and promoting the production of lipoxin A4 (LXA4). On the other hand, Penyanling regulated the activity of NF-κB signal pathway on the LPS-stimulated THP-1 cell line, which suggested the potential mechanism of its anti-inflammatory effect. Besides, it could promote the expression of formyl peptide receptor 2 (FPR2), which suggested its effect on enhancing the resolution of inflammation. Seventy-six substances were identified by their accurate molecular weights, mass fragment patterns, retention times, and standards if available. Most of these substances were flavonoids, phenolics, saponins, and alkaloids. The contents of total flavonoids, phenolics, and saponins within Penyanling were 0.186, 1.371, and 4.321 mg/mL, respectively. CONCLUSION: Penyanling showed an anti-inflammatory effect on PID, and its potential mechanism involved suppressing NF-κB signal pathway and promoting the resolution of inflammation. The main substances within it were flavonoids, phenolics, saponins, and alkaloids.


Asunto(s)
Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , Inflamación/tratamiento farmacológico , Enfermedad Inflamatoria Pélvica/tratamiento farmacológico , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Modelos Animales de Enfermedad , Femenino , Humanos , Lipopolisacáridos , Medicina China Tradicional , FN-kappa B/metabolismo , Enfermedad Inflamatoria Pélvica/patología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Células THP-1
20.
J Ethnopharmacol ; 266: 113407, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-32979413

RESUMEN

ETHNOPHARMACOLOGIAL RELEVANCE: Although Damsissa (Ambrosia maritima) is traditionally used as anti-inflammatory and diuretic, the biological activity and mechanism of action of its major constituents are to be elucidated. AIM: to decipher the anti-arthritic potential of damsin (DMS) and neoambrosin (NMS) and to unfold their molecular signaling in complete Freund's adjuvant (CFA)-induced arthritis model. MATERIALS AND METHODS: the right hind paw was inoculated with CFA (0.1 ml) at day 0 and 7 while treatments were started from the 14th day and continued for 2 weeks. Rats were randomly assigned into 4 groups; normal group (NRML), CFA-induced arthritis group, CFA-induced arthritis treated with DMS and NMS (10 mg/kg/day) as 3rd and 4th group; respectively. RESULTS: Throughout experimental period, treatments ameliorated the increase of paw volume, knee joint diameter and nociception tests as reflected in open field arena. Also, DSM and NMS suppressed phosphorylation of Akt, STAT-3, ERK1/2 which was further mirrored by inactivation of GSK3ß and downregulation of MCP-1 together with CCN1 and NF-kß in hind paw tissue. Concomitantly, inflammation markers; TNF-α, IL-6, -12 were lowered as confirmed microscopically during examination of hind paw tissue. CONCLUSION: DSM and NMS-induced suppression of NF-kß subdues clinical features of RA most probably through repression of Akt/ERK1/2/STAT3 pathway. Therefore, DMS and NMS can serve as safe and effective treatment for rheumatoid arthritis, one of the most disabling chronic, inflammatory and painful autoimmune disease.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Azulenos/farmacología , Inflamación/tratamiento farmacológico , Lactonas/farmacología , Sesquiterpenos/farmacología , Ambrosia/química , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Artritis Reumatoide/patología , Azulenos/aislamiento & purificación , Citocinas/metabolismo , Adyuvante de Freund , Inflamación/patología , Mediadores de Inflamación/metabolismo , Lactonas/aislamiento & purificación , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar , Factor de Transcripción STAT3/metabolismo , Sesquiterpenos/aislamiento & purificación
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