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1.
J Nat Prod ; 87(7): 1725-1734, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-38889235

RESUMEN

Despite millennia of therapeutic plant use, deliberate exploitation of Cannabis's diverse biomedical potential has only recently gained attention. Bioactivity studies focus mainly on cannabidiol (CBD) and tetrahydrocannabinol (THC) with limited information about the broader cannabinome's "minor phytocannabinoids". In this context, our research targeted the synthesis of minor cannabinoids containing a lateral chain with 3 or 4 carbon atoms, focusing on cannabigerol (CBG) and cannabichromene (CBC) analogues. Using known and innovative strategies, we achieved the synthesis of 11 C3 and C4 analogues, five of which were inhibitors of skin inflammation, with the CBG-C4 ester derivative emerging as the most potent compound.


Asunto(s)
Cannabinoides , Cannabinoides/farmacología , Cannabinoides/síntesis química , Cannabinoides/química , Humanos , Estructura Molecular , Animales , Ratones , Piel/efectos de los fármacos , Cannabidiol/farmacología , Cannabidiol/síntesis química , Cannabidiol/química , Cannabis/química , Inflamación/tratamiento farmacológico
2.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38731983

RESUMEN

Acne vulgaris is a prevalent skin disorder affecting many young individuals, marked by keratinization, inflammation, seborrhea, and colonization by Cutibacterium acnes (C. acnes). Ellagitannins, known for their antibacterial and anti-inflammatory properties, have not been widely studied for their anti-acne effects. Chestnut (Castanea sativa Mill., C. sativa), a rich ellagitannin source, including castalagin whose acne-related bioactivity was previously unexplored, was investigated in this study. The research assessed the effect of C. sativa leaf extract and castalagin on human keratinocytes (HaCaT) infected with C. acnes, finding that both inhibited IL-8 and IL-6 release at concentrations below 25 µg/mL. The action mechanism was linked to NF-κB inhibition, without AP-1 involvement. Furthermore, the extract displayed anti-biofilm properties and reduced CK-10 expression, indicating a potential role in mitigating inflammation, bacterial colonization, and keratosis. Castalagin's bioactivity mirrored the extract's effects, notably in IL-8 inhibition, NF-κB inhibition, and biofilm formation at low µM levels. Other polyphenols, such as flavonol glycosides identified via LC-MS, might also contribute to the extract's biological activities. This study is the first to explore ellagitannins' potential in treating acne, offering insights for developing chestnut-based anti-acne treatments pending future in vivo studies.


Asunto(s)
Acné Vulgar , Fagaceae , Taninos Hidrolizables , Extractos Vegetales , Hojas de la Planta , Humanos , Taninos Hidrolizables/farmacología , Fagaceae/química , Acné Vulgar/microbiología , Acné Vulgar/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/química , Hojas de la Planta/química , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , FN-kappa B/metabolismo , Células HaCaT , Propionibacterium acnes/efectos de los fármacos , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Interleucina-8/metabolismo
3.
Molecules ; 29(16)2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39203029

RESUMEN

Castanea sativa Mill. (C. sativa) processing and pruning generate several by-products, including leaves, burs, and shells (inner and outer teguments), which are considered an important source of high-value phytochemicals. Ellagitannins from C. sativa leaf extracts have been described to impair H. pylori viability and inflammation in gastric cells. Furthermore, chestnut shells showed an important anti-inflammatory effect in gastric epithelial cells. Dietary polyphenols, including tannins, have been reported to interfere with targets of inflammation, including the nuclear factor κB (NF-κB). A promising role as a further therapeutical target for gut disorders has been recently proposed for the regulatory subunit of hypoxia-inducible factor (HIF-1α), as a potential stabilizer of intestinal barrier integrity. Therefore, the main objective of this work is the chemical characterization of several chestnut by-products (bud, spiny bur, wood, pericarp and episperm), together with the exploitation of their anti-inflammatory properties in intestinal cells, scavenging capacity, and stability following gastrointestinal digestion. The chemical characterization confirmed the presence of bioactive polyphenols in the extracts, including ellagitannins. In CaCo-2 cells stimulated by an IL-1ß-IFN-γ cocktail, nearly all chestnut by-products (50 µg/mL) inhibited the release of proinflammatory mediators (CXCL-10, IL-8, MCP-1, ICAM), along with the NF-κB-driven transcription, and induced the HRE-driven transcription. The stability of the most promising extracts, identified through PCA and cluster analysis, was addressed by in vitro gastrointestinal digestion. Despite the significant reduction in total polyphenol index of chestnut bud and wood after gastric and intestinal digestion, the activity of these extracts on both scavenging and anti-inflammatory parameters remained promising. These data contribute to exploit the potential of chestnut by-products as sources of dietary polyphenols with anti-inflammatory properties at the intestinal level. Moreover, this study could represent an important step to encourage the recycling and valorization of chestnut by-products, promoting the circular economy and reducing the environmental impact related to the management of agriculture waste.


Asunto(s)
Antiinflamatorios , Fagaceae , Extractos Vegetales , Humanos , Fagaceae/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Células CACO-2 , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Polifenoles/farmacología , Polifenoles/química , Taninos Hidrolizables/farmacología , Taninos Hidrolizables/química , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , FN-kappa B/metabolismo
4.
Int J Mol Sci ; 24(13)2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37446392

RESUMEN

Hydroxylysine glycosylations are post-translational modifications (PTMs) essential for the maturation and homeostasis of fibrillar and non-fibrillar collagen molecules. The multifunctional collagen lysyl hydroxylase 3 (LH3/PLOD3) and the collagen galactosyltransferase GLT25D1 are the human enzymes that have been identified as being responsible for the glycosylation of collagen lysines, although a precise description of the contribution of each enzyme to these essential PTMs has not yet been provided in the literature. LH3/PLOD3 is thought to be capable of performing two chemically distinct collagen glycosyltransferase reactions using the same catalytic site: an inverting beta-1,O-galactosylation of hydroxylysines (Gal-T) and a retaining alpha-1,2-glucosylation of galactosyl hydroxylysines (Glc-T). In this work, we have combined indirect luminescence-based assays with direct mass spectrometry-based assays and molecular structure studies to demonstrate that LH3/PLOD3 only has Glc-T activity and that GLT25D1 only has Gal-T activity. Structure-guided mutagenesis confirmed that the Glc-T activity is defined by key residues in the first-shell environment of the glycosyltransferase catalytic site as well as by long-range contributions from residues within the same glycosyltransferase (GT) domain. By solving the molecular structures and characterizing the interactions and solving the molecular structures of human LH3/PLOD3 in complex with different UDP-sugar analogs, we show how these studies could provide insights for LH3/PLOD3 glycosyltransferase inhibitor development. Collectively, our data provide new tools for the direct investigation of collagen hydroxylysine PTMs and a comprehensive overview of the complex network of shapes, charges, and interactions that enable LH3/PLOD3 glycosyltransferase activities, expanding the molecular framework and facilitating an improved understanding and manipulation of glycosyltransferase functions in biomedical applications.


Asunto(s)
Glicosiltransferasas , Hidroxilisina , Humanos , Glicosiltransferasas/genética , Hidroxilisina/metabolismo , Glicosilación , Colágeno/metabolismo , Lisina/metabolismo
5.
Int J Mol Sci ; 24(20)2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37894827

RESUMEN

Helicobacter pylori is a leading cause of chronic gastric inflammation, generally associated with gastritis and adenocarcinoma. Activation of the NF-κB pathway mainly contributes to the inflammatory phenotype observed in H. pylori infection in humans and experimental models. Since the gastric epithelium undergoes rapid turnover, inflammation and pathogenicity of H. pylori result from early phase and chronically activated pathways. In the present study we investigated the early host response to H. pylori in non-tumoral human gastric epithelial cells (GES-1). To dissect the pathogen-specific mechanisms we also examined the response to tumor necrosis factor (TNF), a prototypical cytokine. By analyzing the activation state of NF-κB signaling, cytokine expression and secretion, and the transcriptome, we found that the inflammatory response of GES-1 cells to H. pylori and TNF results from activation of multiple pathways and transcription factors, e.g., NF-κB and CCAAT/enhancer-binding proteins (CEBPs). By comparing the transcriptomic profiles, we found that H. pylori infection induces a less potent inflammatory response than TNF but affects gene transcription to a greater extent by specifically inducing transcription factors such as CEBPß and numerous zinc finger proteins. Our study provides insights on the cellular pathways modulated by H. pylori in non-tumoral human gastric cells unveiling new potential targets.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , FN-kappa B/metabolismo , Infecciones por Helicobacter/complicaciones , Células Epiteliales/metabolismo , Inflamación/metabolismo , Mucosa Gástrica/metabolismo , Citocinas/metabolismo
6.
Int J Mol Sci ; 24(17)2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37686340

RESUMEN

Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE-AAT) in which the two proteins are covalently bound. The lack of this complex, together with the detection of HNE activity in BALf/plasma samples of COVID-19 patients, leads us to hypothesize that potential functional deficiencies should necessarily be attributed to possible structural modifications of AAT. These could greatly diminish its ability to inhibit neutrophil elastase, thus reducing lung protection. The aim of this work was to explore the oxidation state of AAT in BALf/plasma samples from these patients so as to understand whether the deficient inhibitory activity of AAT was somehow related to possible conformational changes caused by the presence of abnormally oxidized residues.


Asunto(s)
COVID-19 , Elastasa de Leucocito , Humanos , SARS-CoV-2 , Oxidación-Reducción , Transporte Biológico
7.
Curr Issues Mol Biol ; 44(5): 2122-2138, 2022 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-35678672

RESUMEN

Neutrophils play a pathogenic role in COVID-19 by releasing Neutrophils Extracellular Traps (NETs) or human neutrophil elastase (HNE). Given that HNE is inhibited by α1-antitrypsin (AAT), we aimed to assess the content of HNE, α1-antitrypsin (AAT) and HNE-AAT complexes (the AAT/HNE balance) in 33 bronchoalveolar lavage fluid (BALf) samples from COVID-19 patients. These samples were submitted for Gel-Electrophoresis, Western Blot and ELISA, and proteins (bound to AAT or HNE) were identified by Liquid Chromatography-Mass Spectrometry. NETs' release was analyzed by confocal microscopy. Both HNE and AAT were clearly detectable in BALf at high levels. Contrary to what was previously observed in other settings, the formation of HNE-AAT complex was not detected in COVID-19. Rather, HNE was found to be bound to acute phase proteins, histones and C3. Due to the relevant role of NETs, we assessed the ability of free AAT to bind to histones. While confirming this binding, AAT was not able to inhibit NET formation. In conclusion, despite the finding of a high burden of free and bound HNE, the lack of the HNE-AAT inhibitory complex in COVID-19 BALf demonstrates that AAT is not able to block HNE activity. Furthermore, while binding to histones, AAT does not prevent NET formation nor their noxious activity.

8.
Planta Med ; 88(7): 492-506, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33851375

RESUMEN

The use of Cannabis sativa is currently recognized to ease certain types of chronic pain, reduce chemotherapy-induced nausea, and improve anxiety. Nevertheless, few studies highlighted the therapeutic potential of C. sativa extracts and related phytocannabinoids for a variety of widespread skin disorders including acne, atopic dermatitis, psoriasis, pruritus, and pain. This review summarized the current evidence on the effects of phytocannabinoids at the cutaneous level through the collection of in vitro, in vivo, and clinical studies published on PubMed, Scopus, Embase, and Web of Science until October 2020. Phytocannabinoids have demonstrated potential anti-inflammatory, antioxidant, anti-aging, and anti-acne properties by various mechanisms involving either CB1/2-dependent and independent pathways. Not only classical immune cells, but also several skin-specific actors, such as keratinocytes, fibroblasts, melanocytes, and sebocytes, may represent a target for phytocannabinoids. Cannabidiol, the most investigated compound, revealed photoprotective, antioxidant, and anti-inflammatory mechanisms at the cutaneous level, while the possible impact on cell differentiation, especially in the case of psoriasis, would require further investigation. Animal models and pilot clinical studies supported the application of cannabidiol in inflammatory-based skin diseases. Also, one of the most promising applications of non-psychotropic phytocannabinoids is the treatment of seborrheic disorders, especially acne. In conclusion, the incomplete knowledge of the role of the endocannabinoid system in skin disorders emerged as an important limit for pharmacological investigations. Moreover, the limited studies conducted on C. sativa extracts suggested a higher potency than single phytocannabinoids, thus stimulating new research on phytocannabinoid interaction.


Asunto(s)
Acné Vulgar , Cannabidiol , Cannabinoides , Cannabis , Psoriasis , Acné Vulgar/tratamiento farmacológico , Animales , Antioxidantes/uso terapéutico , Cannabidiol/uso terapéutico , Cannabinoides/farmacología , Cannabinoides/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Psoriasis/tratamiento farmacológico
9.
Int J Mol Sci ; 23(16)2022 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-36012541

RESUMEN

Hamamelis virginiana L. bark extract is a traditional remedy for skin affections, including atopic dermatitis/eczema (AD). Hamamelis preparations contain tannins, including hamamelitannin (HT), although their pharmacological role in AD is still unknown. This study aimed to study the rational for its topical use by considering the impact of crucial biomarkers on AD pathogenesis. A standardized extract (HVE) (0.5−125 µg/mL) was compared to hamamelitannin (HT), its main compound (0.5−5 µg/mL), in a model of human keratinocytes (HaCaTs), challenged with an AD-like cytokine milieu (TNF-α, IFN-γ, and IL-4). HVE inhibited the release of mediators involved in skin autoimmunity (IL-6 and IL-17C) and allergy (TSLP, IL-6, CCL26, and MMP-9) with a concentration-dependent fashion (IC50s < 25 µg/mL). The biological mechanism was ascribed, at least in part, to the impairment of the NF-κB-driven transcription. Moreover, HVE counteracted the proliferative effects of IL-4 and recovered K10, a marker of skin differentiation. Notably, HT showed activity on well-known targets of IL-4 pathway (CCL26, K10, cell proliferation). To the best of our knowledge, this work represents the first demonstration of the potential role of Hamamelis virginiana in the control of AD symptoms, such as itch and skin barrier impairment, supporting the relevance of the whole phytocomplex.


Asunto(s)
Dermatitis Atópica , Hamamelis , Citocinas/farmacología , Dermatitis Atópica/tratamiento farmacológico , Humanos , Interleucina-4/farmacología , Interleucina-6/farmacología , Queratinocitos , Corteza de la Planta , Extractos Vegetales/farmacología , Piel
10.
Molecules ; 27(21)2022 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-36364420

RESUMEN

Plants rich in hydrolyzable tannins were traditionally used all over the world for a variety of chronic inflammatory disorders, including arthritis, colitis, and dermatitis. However, the knowledge of their immunological targets is still limited though fundamental for their rational use in phytotherapy. The recent advances regarding the pathogenesis of inflammatory-based diseases represent an opportunity to elucidate the pharmacological mechanism of plant-derived metabolites with immunomodulatory activity. This review collects recent articles regarding the role of hydrolyzable tannins and their gut metabolites in Th1, Th2, and Th17 inflammatory responses. In line with the traditional use, rheumatoid arthritis (RA), inflammatory bowel diseases (IBDs), psoriasis, atopic dermatitis (AD), and asthma were the most investigated diseases. A substantial body of in vivo studies suggests that, beside innate response, hydrolyzable tannins may reduce the levels of Th-derived cytokines, including IFN-γ, IL-17, and IL-4, following oral administration. The mode of action is multitarget and may involve the impairment of inflammatory transcription factors (NF-κB, NFAT, STAT), enzymes (MAPKs, COX-2, iNOS), and ion channels. However, their potential impact on pathways with renewed interest for inflammation, such as JAK/STAT, or the modulation of the gut microbiota demands dedicate studies.


Asunto(s)
Artritis Reumatoide , Dermatitis Atópica , Humanos , Taninos Hidrolizables/farmacología , Células Th17 , Citocinas/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Dermatitis Atópica/metabolismo
11.
Biochem Soc Trans ; 49(2): 855-866, 2021 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-33704379

RESUMEN

Collagen is a major constituent of the extracellular matrix (ECM) that confers fundamental mechanical properties to tissues. To allow proper folding in triple-helices and organization in quaternary super-structures, collagen molecules require essential post-translational modifications (PTMs), including hydroxylation of proline and lysine residues, and subsequent attachment of glycan moieties (galactose and glucose) to specific hydroxylysine residues on procollagen alpha chains. The resulting galactosyl-hydroxylysine (Gal-Hyl) and less abundant glucosyl-galactosyl-hydroxylysine (Glc-Gal-Hyl) are amongst the simplest glycosylation patterns found in nature and are essential for collagen and ECM homeostasis. These collagen PTMs depend on the activity of specialized glycosyltransferase enzymes. Although their biochemical reactions have been widely studied, several key biological questions about the possible functions of these essential PTMs are still missing. In addition, the lack of three-dimensional structures of collagen glycosyltransferase enzymes hinders our understanding of the catalytic mechanisms producing this modification, as well as the impact of genetic mutations causing severe connective tissue pathologies. In this mini-review, we summarize the current knowledge on the biochemical features of the enzymes involved in the production of collagen glycosylations and the current state-of-the-art methods for the identification and characterization of this important PTM.


Asunto(s)
Colágeno/metabolismo , Glicosiltransferasas/metabolismo , Hidroxilisina/metabolismo , Procesamiento Proteico-Postraduccional , Animales , Colágeno/química , Glicosilación , Humanos , Hidroxilisina/química , Modelos Químicos , Estructura Molecular , Especificidad por Sustrato
12.
Molecules ; 26(10)2021 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-34065200

RESUMEN

Ribes nigrum L. (blackcurrant) leaf extracts, due to high levels of flavonols and anthocyanins, have been shown to exhibit beneficial effects in inflammatory diseases. However, whereas their traditional use has been investigated and validated in several models of inflammation and oxidative stress, the possible impact on skin disorders is still largely unknown. The purpose of this work was to elucidate the effects of R. nigrum leaf extract (RNLE) on keratinocyte-derived inflammatory mediators, elicited by a Th1 or Th2 cytokine milieu. HaCaT cells were challenged with TNF-α, either alone or in combination with the costimulatory cytokines IFN-γ or IL-4, and the release of proinflammatory cytokines and mediators (IL-8, IL-6, s-ICAM-1, and TSLP) was evaluated. The results showed that RNLE preferentially interferes with IFN-γ signaling, demonstrating only negligible activity on TNF-α or IL-4. This effect was attributed to flavonols, which might also account for the ability of RNLE to impair TNF-α/IL-4-induced TSLP release in a cAMP-independent manner. These results suggest that RNLE could have an antiallergic effect mediated in keratinocytes via mechanisms beyond histamine involvement. In conclusion, the discovery of RNLE preferential activity against IFN-γ-mediated inflammation suggests potential selectivity against Th1 type response and the possible use in Th1 inflammatory diseases.


Asunto(s)
Inflamación/inducido químicamente , Interferón gamma/farmacología , Queratinocitos/efectos de los fármacos , Extractos Vegetales/farmacología , Hojas de la Planta/química , Ribes/química , Línea Celular , Citocinas/administración & dosificación , Citocinas/metabolismo , Humanos , Mediadores de Inflamación/administración & dosificación , Mediadores de Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Quempferoles/farmacología , Queratinocitos/metabolismo , FN-kappa B/metabolismo , Quercetina/farmacología
13.
Electrophoresis ; 40(1): 151-164, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30216498

RESUMEN

Detection of proteins which may be potential biomarkers of disorders represents a big step forward in understanding the molecular mechanisms that underlie pathological processes. In this context proteomics plays the important role of opening a path for the identification of molecular signatures that can potentially assist in early diagnosis of several clinical disturbances. Aim of this report is to provide an overview of the wide variety of proteomic strategies that have been applied to the investigation of chronic obstructive pulmonary disease (COPD), a severe disorder that causes an irreversible damage to the lungs and for which there is no cure yet. The results in this area published over the past decade show that proteomics indeed has the ability of monitoring alterations in expression profiles of proteins from fluids/tissues of patients affected by COPD and healthy controls. However, these data also suggest that proteomics, while being an attractive tool for the identification of novel pathological mediators of COPD, remains a technique mainly generated and developed in research laboratories. Great efforts dedicated to the validation of these biological signatures will result in the proof of their clinical utility.


Asunto(s)
Biomarcadores , Proteómica/métodos , Enfermedad Pulmonar Obstructiva Crónica , Biomarcadores/análisis , Biomarcadores/metabolismo , Líquido del Lavado Bronquioalveolar/química , Cromatografía Liquida , Electroforesis Capilar , Femenino , Humanos , Masculino , Espectrometría de Masas , Proteoma/análisis , Proteoma/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo
14.
J Chem Ecol ; 45(8): 673-683, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31407198

RESUMEN

Animals modulate intraspecific signal shape and intensity, notably during reproductive periods. Signal variability typically follows a seasonal scheme, traceable through the expression of visual, acoustic, chemical and behavioral patterns. The chemical channel is particularly important in lizards, as demonstrated by well-developed epidermal glands in the cloacal region that secrete lipids and proteins recognized by conspecifics. In males, the seasonal pattern of gland activity is underpinned by variation of circulating androgens. Changes in the composition of lipid secretions convey information about the signaler's quality (e.g., size, immunity). Presumably, individual identity is associated with a protein signature present in the femoral secretions, but this has been poorly investigated. For the first time, we assessed the seasonal variability of the protein signal in relation to plasma testosterone level (T), glandular activity and the concentration of provitamin D3 in the lipid fraction. We sampled 174 male common wall lizards (Podarcis muralis) over the entire activity season. An elevation of T was observed one to two months before the secretion peak of lipids during the mating season; such expected delay between hormonal fluctuation and maximal physiological response fits well with the assumption that provitamin D3 indicates individual quality. One-dimensional electrophoretic analysis of proteins showed that gel bands were preserved over the season with an invariant region; a result in agreement with the hypothesis that proteins are stable identity signals. However, the relative intensity of bands varied markedly, synchronously with that of lipid secretion pattern. These variations of protein secretion suggest additional roles of proteins, an issue that requires further studies.


Asunto(s)
Glándulas Exocrinas/metabolismo , Lípidos/análisis , Lagartos/fisiología , Proteínas de Reptiles/análisis , Animales , Deshidrocolesteroles/análisis , Electroforesis en Gel de Campo Pulsado , Cromatografía de Gases y Espectrometría de Masas , Metabolismo de los Lípidos , Lípidos/química , Masculino , Análisis de Componente Principal , Estaciones del Año , Conducta Sexual Animal , Testosterona/sangre
15.
Mediators Inflamm ; 2019: 6173893, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31341420

RESUMEN

Atherosclerosis is characterized by interaction between immune and vascular endothelial cells which is mediated by adhesion molecules occurring on the surface of the vascular endothelium leading to massive release of proinflammatory mediators. Ginkgo biloba L. (Ginkgoaceae) standardized extracts showing beneficial effects are commonly prepared by solvent extraction, and acetone is used according to the European Pharmacopoeia recommendations; the well-known Ginkgo biloba acetone extract EGb761® is the most clinically investigated. However, in some countries, the allowed amount of solvent is limited to ethanol, thus implying that the usage of a standardized Ginkgo biloba ethanol extract may be preferred in all those cases, such as for food supplements. The present paper investigates if ethanol and acetone extracts, with comparable standardization, may be considered comparable in terms of biological activity, focusing on the radical scavenging and anti-inflammatory activities. Both the extracts showed high inhibition of TNFα-induced VCAM-1 release (41.1-43.9 µg/mL), which was partly due to the NF-κB pathway impairment. Besides ROS decrease, cAMP increase following treatment with ginkgo extracts was addressed and proposed as further molecular mechanism responsible for the inhibition of endothelial E-selectin. No statistical difference was observed between the extracts. The present study demonstrates for the first time that ethanol and acetone extracts show comparable biological activities in human endothelial cell, thus providing new insights into the usage of ethanol extracts in those countries where restrictions in amount of acetone are present.


Asunto(s)
Endotelio Vascular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Acetona , Transporte Activo de Núcleo Celular , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Aterosclerosis/tratamiento farmacológico , AMP Cíclico/metabolismo , Selectina E/metabolismo , Etanol , Regulación de la Expresión Génica , Ginkgo biloba , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inflamación/tratamiento farmacológico , FN-kappa B/metabolismo , Fosforilación , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo
16.
Phytother Res ; 33(8): 2083-2093, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31250491

RESUMEN

Skin inflammatory diseases result from complex events that include dysregulation and abnormal expression of inflammatory mediators or their receptors in skin cells. The present study investigates the potential effect of a Cannabis sativa L. ethanolic extract standardized in cannabidiol as antiinflammatory agent in the skin, unraveling the molecular mechanisms in human keratinocytes and fibroblasts. The extract inhibited the release of mediators of inflammation involved in wound healing and inflammatory processes occurring in the skin. The mode of action involved the impairment of the nuclear factor-kappa B (NF-κB) pathway since the extract counteracted the tumor necrosis factor-alpha-induced NF-κB-driven transcription in both skin cell lines. Cannabis extract and cannabidiol showed different effects on the release of interleukin-8 and vascular endothelial growth factor, which are both mediators whose genes are dependent on NF-κB. The effect of cannabidiol on the NF-κB pathway and metalloproteinase-9 (MMP-9) release paralleled the effect of the extract thus making cannabidiol the major contributor to the effect observed. Down-regulation of genes involved in wound healing and skin inflammation was at least in part due to the presence of cannabidiol. Our findings provide new insights into the potential effect of Cannabis extracts against inflammation-based skin diseases.


Asunto(s)
Cannabidiol/química , Cannabis/química , Inflamación/tratamiento farmacológico , Extractos Vegetales/química , Piel/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Humanos , Piel/patología
17.
Pharmacol Res ; 134: 145-155, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29928974

RESUMEN

Gastritis is a widely spread inflammatory disease, mostly caused by Helicobacter pylori infection. Release of IL-8 by the stomach epithelium is a hallmark of gastritis and contributes to the amplification of the inflammatory state. Pharmacological modulation of IL-8 release is a strategy to relieve gastric inflammation and prevent more severe clinical outcomes. In search of nutraceuticals with potential anti-gastritis properties we used a bio-guided approach based on IL-8 secretion by gastric cells to characterize extracts from the fruits of different chestnut varieties. We found that the ability to inhibit IL-8 secretion correlated with the amount of proanthocyanidins and was associated to the not edible parts of chestnut in all the tested varieties. We also found that the anti-inflammatory activity is preserved upon mild thermal treatment and after in vitro simulated gastric digestion. By combining a robust bio-guided approach with a comprehensive analysis of the tannin fraction of chestnut extracts, we provide evidence for the potential use of chestnut-based nutraceuticals in human gastritis. The bioactive components of chestnut fruits inhibit IL-8 secretion by impairing NF-κB signaling and by other mechanisms, thus opening new applications of proanthocyanidins for inflammation-based diseases.


Asunto(s)
Aesculus/química , Antiinflamatorios/farmacología , Bioensayo/métodos , Suplementos Dietéticos , Mucosa Gástrica/efectos de los fármacos , Gastritis/tratamiento farmacológico , Extractos Vegetales/farmacología , Proantocianidinas/farmacología , Antiinflamatorios/aislamiento & purificación , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Frutas , Mucosa Gástrica/inmunología , Mucosa Gástrica/metabolismo , Gastritis/inmunología , Gastritis/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-8/metabolismo , Extractos Vegetales/aislamiento & purificación , Proantocianidinas/aislamiento & purificación , Vías Secretoras
18.
Neurourol Urodyn ; 37(8): 2606-2613, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29664139

RESUMEN

OBJECTIVE: The aim of this study was to evaluate the reliability of different dynamometric variables of the pelvic floor muscles (PFM) in healthy women during different periods of menstrual cycle. MATERIALS AND METHODS: Vaginal dynamometric equipment was developed by the authors and its reproducibility was tested. The PFM contractions of 20 healthy women were collected by two independent examiners over three consecutive weeks, always on the same day, with a seven-day interval between readings, starting from the first day after the end of the menstrual period. For the measurements, the branch of the dynamometer was positioned first on the sagittal plane and then on the frontal plane. Baseline, peak time, maximum PFM strength, impulse contraction, and average contraction force were calculated. Reproducibility was tested using the intra-class correlation coefficient (ICC) and standard error of measurement. Repeated-measures ANOVA was used to compare the data from different days. RESULTS: For intra-day and inter-day reliability between examiners, all the parameters collected on the sagittal plane presented good and excellent reproducibility (ICC2,1 = 0.60 to 0.98), whereas reproducibility on the frontal plane was respectively poor and excellent (ICC2,1 = 0.23 to 0.97). The ANOVA revealed significant differences between sessions only for the impulse of contraction for the sagittal (P = 0.005) and frontal (P = 0.03) planes. CONCLUSIONS: Time and contraction force parameters of the PFM are not influenced by hormonal alterations that occur during the menstrual cycle. The impulse of contraction was the only variable to demonstrate a significant difference between the first and second week of the data collection protocol. The baseline, maximum strength value, impulse of contraction, and average contraction force variables presented good to excellent reproducibility and can be safely used as a method of PFM evaluation.


Asunto(s)
Ciclo Menstrual/fisiología , Contracción Muscular/fisiología , Diafragma Pélvico/fisiología , Adulto , Femenino , Voluntarios Sanos , Humanos , Dinamómetro de Fuerza Muscular , Reproducibilidad de los Resultados , Adulto Joven
19.
Lasers Med Sci ; 33(4): 737-744, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29204914

RESUMEN

Although low-level laser therapy (LLLT) is an important resource for the treatment of non-specific neck pain patients, the dose which presents the greatest therapeutic potential for the treatment of this pathology is still unclear. The present study aimed to evaluate the immediate effect of LLLT on the muscle fiber conduction velocity (MFCV) and electromyographic activity (EMG) of the upper trapezius (UT) muscle in healthy individuals. A total of 20 healthy subjects were enrolled in a randomized, double-blind, crossover study. Active LLLT (820 nm wavelength, 30 mW, energy total 18 J) or placebo LLLT (pLLLT) was delivered on the UT muscle. Each subject was subjected to a single session of active LLLT and pLLLT. Surface electromyography (sEMG) signal of the UT muscle was recorded during five different step contractions of shoulder elevation force (10-30% maximal voluntary contraction) pre- and post-LLLT irradiation. The values of MFCV and sEMG global amplitude (RMSG) were used to calculate the effects of LLLT. The results showed no difference in the MFCV comparing the LLLT and pLLLT groups (F = 0.72 p = 0.39, η p2 = 0.004). However, a significant difference was observed in the RMSG between the LLLT and pLLLT (F 1,2 = 16.66; P < 0.0001, η p2 = 0.09). Individuals who received active LLLT presented a significant decrease in RMSG after laser application (F = 61.28; p < 0.0001, η p2 = 0.43). In conclusion, the 820 nm LLLT, with energy total of 18 J, did not alter the MFCV but significantly reduced the sEMG signal amplitude of the upper trapezius muscle in healthy subjects to a level of up to 30% of maximal voluntary contraction.


Asunto(s)
Electromiografía , Terapia por Luz de Baja Intensidad/métodos , Fibras Musculares Esqueléticas/fisiología , Fibras Musculares Esqueléticas/efectos de la radiación , Vértebras Cervicales/efectos de la radiación , Estudios Cruzados , Método Doble Ciego , Femenino , Voluntarios Sanos , Humanos , Masculino , Placebos , Adulto Joven
20.
J Manipulative Physiol Ther ; 41(3): 208-217, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29549891

RESUMEN

OBJECTIVE: The objective of this study was to assess changes in upper trapezius myoelectric activity and pain in patients with nonspecific neck pain after a single session of acupuncture (ACP). METHODS: A blinded randomized clinical trial was conducted. Fifteen patients with nonspecific neck pain and 15 healthy participants were enrolled in a randomized, single-blinded, crossover study. Each participant was subjected to a single session of ACP and sham acupuncture (SACP). The electromyography (EMG) signal of the upper trapezius muscle was recorded during different step contractions of shoulder elevation force (15%-30% maximal voluntary contraction) before and after ACP treatment. RESULTS: Significant effects were confirmed after the treatment (ACP and SACP) for Numeric Rating Scale scores (F1,28 = 51.61; P < .0001) and pain area (F1,2 = 32.03; P < .0001). Significant decreases in the EMG amplitude were identified for the nonspecific neck pain group (NPG) (F1,112 = 26.82; P < .0001) and the healthy participant group (HPG) (F1,112 = 21.69; P < .0001) after ACP treatment. No differences were identified between the ACP and SACP treatment protocols for Numeric Rating Scale score (NPG: F1,28 = 0.95; P = .33), pain area (NPG: F1,28 = 1.97; P = .17), or EMG amplitude (NPG: F1,112 = 0.47; P = .49; HPG: F1,112 = 0.75; P = .38). CONCLUSION: The effect of ACP at acupoints triple energizer 5 and large intestine 11 triple energizer 5, or in close proximity, contributes to pain relief among patients with nonspecific neck pain. The electromyographic analysis indicated a greater resistance to muscle fatigue and decrease of activity of the upper trapezius muscle among healthy participants and patients with nonspecific neck pain.


Asunto(s)
Terapia por Acupuntura/métodos , Electromiografía/métodos , Dolor de Cuello/terapia , Músculos Superficiales de la Espalda/fisiopatología , Puntos de Acupuntura , Adulto , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiología , Manejo del Dolor , Rango del Movimiento Articular , Método Simple Ciego
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