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1.
J Electrocardiol ; 83: 95-105, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38387106

RESUMO

Electrocardiographic patterns of right bundle branch and fascicular blocks were comprehensively analyzed in a two-phase study. The research aimed to address the scarcity of literature and the absence of standardized diagnostic criteria for these conditions. It revealed a weak correlation between the cardiac axis and age and highlighted the high misdiagnosis rate of these blocks. Furthermore, it discussed the challenges in fulfilling existing diagnostic criteria. The study emphasizes the need for a more precise understanding of right ventricular conduction disorders and the importance of developing robust diagnostic criteria.


Assuntos
Bloqueio de Ramo , Eletrocardiografia , Humanos , Bloqueio de Ramo/diagnóstico , Sistema de Condução Cardíaco , Ventrículos do Coração
2.
Brain Behav Immun ; 112: 188-205, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37329995

RESUMO

Whether or not SARS-CoV-2 can cross from mother to fetus during a prenatal infection has been controversial; however, recent evidence such as viral RNA detection in umbilical cord blood and amniotic fluid, as well as the discovery of additional entry receptors in fetal tissues suggests a potential for viral transmission to and infection of the fetus. Furthermore, neonates exposed to maternal COVID-19 during later development have displayed neurodevelopmental and motor skill deficiencies, suggesting the potential for consequential neurological infection or inflammation in utero. Thus, we investigated transmission potential of SARS-CoV-2 and the consequences of infection on the developing brain using human ACE2 knock-in mice. In this model, we found that viral transmission to the fetal tissues, including the brain, occurred at later developmental stages, and that infection primarily targeted male fetuses. In the brain, SARS-CoV-2 infection largely occurred within the vasculature, but also within other cells such as neurons, glia, and choroid plexus cells; however, viral replication and increased cell death were not observed in fetal tissues. Interestingly, early gross developmental differences were observed between infected and mock-infected offspring, and high levels of gliosis were seen in the infected brains 7 days post initial infection despite viral clearance at this time point. In the pregnant mice, we also observed more severe COVID-19 infections, with greater weight loss and viral dissemination to the brain, compared to non-pregnant mice. Surprisingly, we did not observe an increase in maternal inflammation or the antiviral IFN response in these infected mice, despite showing clinical signs of disease. Overall, these findings have concerning implications regarding neurodevelopment and pregnancy complications of the mother following prenatal COVID-19 exposure.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Gravidez , Feminino , Masculino , Humanos , Animais , Camundongos , SARS-CoV-2 , Encéfalo , Inflamação
3.
Molecules ; 28(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38138560

RESUMO

Diabetes mellitus (DM) is considered one of the major health diseases worldwide, one that requires immediate alternatives to allow treatments for DM to be more effective and less costly for patients and also for health-care systems. Recent approaches propose treatments for DM based on that; in addition to focusing on reducing hyperglycemia, they also consider multitargets, as in the case of plants. Among these, we find the plant known as chia to be highlighted, a crop native to Mexico and one cultivated in Mesoamerica from pre-Hispanic times. The present work contributes to the review of the antidiabetic effects of chia for the treatment of DM. The antidiabetic effects of chia are effective in different mechanisms involved in the complex pathogenesis of DM, including hypoglycemic, antioxidant, and anti-inflammatory mechanisms, and the inhibition of the enzymes α-glucosidase and α-amylase, as well as in the prevention of the risk of cardiovascular disease. The tests reviewed included 16 in vivo assays on rodent models, 13 clinical trials, and 4 in vitro tests. Furthermore, chia represents advantages over other natural products due to its availability and its acceptance and, in addition, as a component of the daily diet worldwide, especially due to its omega-3 fatty acids and its high concentration of dietary fiber. Thus, chia in the present work represents a source of antidiabetic agents that would perhaps be useful in novel clinical treatments.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Salvia , Humanos , alfa-Amilases , alfa-Glucosidases , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Salvia hispanica , Sementes
4.
Molecules ; 28(17)2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37687087

RESUMO

Essential oils (EOs) are complex mixtures of volatile natural compounds. We have extensively studied the EO of Bursera morelensis, which demonstrates antibacterial, antifungal, anti-inflammatory, and wound-healing activities. The objective of this work was to determine the effect of this EO on fibroblast migration in a three-dimensional in vitro model. For the three-dimensional in vitro model, a series of fibrin hydrogel scaffolds (FSs) were built in which fibroblasts were cultured and subsequently stimulated with fibroblast growth factor (FGF) or EO. The results demonstrated that these FSs are appropriate for fibroblast culture, since no decrease in cell viability or changes in cell proliferation were found. The results also showed that this EO promotes cell migration four hours after stimulation, and the formation of cell projections (filopodia) outside the SF was observed. From these results, we confirmed that part of the mechanism of action of the essential oil of B. morelensis during the healing process is the stimulation of fibroblast migration to the wound site.


Assuntos
Bursera , Óleos Voláteis , Óleos Voláteis/farmacologia , Projetos de Pesquisa , Movimento Celular , Fatores de Crescimento de Fibroblastos , Fibroblastos
5.
Molecules ; 27(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35684376

RESUMO

In Mexico, Diabetes mellitus (DM) is a serious health problem, and although the current pharmacological treatments for DM such as insulin and oral hypoglycemics are available, the Mexican population continues to use medicinal plants in the treatment of DM. The antidiabetic properties of the plant species that belong to the Cucurbitaceae family has already been recognized worldwide. Since Mexico is one of the most important centers of diversity of Cucurbitaceae, the present work contributes to the review of the most used species of Cucurbitaceae in the treatment of DM in Mexico. The reviewed species (Cucurbita ficifolia, C. maxima, C. moschata, C. pepo, Ibervillea sonorae, Sechium edule, Citrullus lanatus, Cucumis melo, and C. sativus) revealed that the antidiabetic effects exerted are effective in a number of mechanisms involved in the complex pathogenesis of DM: hypoglycemic, antioxidant, anti-inflammatory, anti-obesity, protective effects on diverse organs and cells, as well as in the control of dyslipidemias; furthermore, the select species of the Cucurbitaceae family could also be essential components of diets for the control of DM in patients with the disease. Thus, the Cucurbitaceae species selected in the present work represent a source of antidiabetic agents that perhaps establish the bases for novel clinical treatments.


Assuntos
Cucurbitaceae , Diabetes Mellitus , Diabetes Mellitus/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina , México
6.
Biol Res ; 54(1): 3, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546773

RESUMO

BACKGROUND: Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake-via AMP-activated protein kinase (AMPK)-after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). METHODS: Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of ß-myosin heavy chain (ß-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). RESULTS: Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated ß-mhc, Hk2 and Pfk2 mRNA levels. CONCLUSION: These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.


Assuntos
Proteínas Quinases Ativadas por AMP , Glucose/metabolismo , Miócitos Cardíacos , Receptores Androgênicos/metabolismo , Testosterona/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células Cultivadas , Hipertrofia , Masculino , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos , Transdução de Sinais
7.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806797

RESUMO

Among multiple mechanisms, low-grade inflammation is critical for the development of insulin resistance as a feature of type 2 diabetes. The nucleotide-binding oligomerization domain-like receptor family (NOD-like) pyrin domain containing 3 (NLRP3) inflammasome has been linked to the development of insulin resistance in various tissues; however, its role in the development of insulin resistance in the skeletal muscle has not been explored in depth. Currently, there is limited evidence that supports the pathological role of NLRP3 inflammasome activation in glucose handling in the skeletal muscle of obese individuals. Here, we have centered our focus on insulin signaling in skeletal muscle, which is the main site of postprandial glucose disposal in humans. We discuss the current evidence showing that the NLRP3 inflammasome disturbs glucose homeostasis. We also review how NLRP3-associated interleukin and its gasdermin D-mediated efflux could affect insulin-dependent intracellular pathways. Finally, we address pharmacological NLRP3 inhibitors that may have a therapeutical use in obesity-related metabolic alterations.


Assuntos
Inflamassomos/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Resistência à Insulina , Músculo Esquelético/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Animais , Transporte Biológico , Doença Crônica , Glucose/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Interleucina-1beta/metabolismo , Metabolismo dos Lipídeos , Músculo Esquelético/patologia , Obesidade/tratamento farmacológico , Obesidade/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
8.
Int J Mol Sci ; 22(19)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34638553

RESUMO

Low-grade chronic inflammation plays a pivotal role in the pathogenesis of insulin resistance (IR), and skeletal muscle has a central role in this condition. NLRP3 inflammasome activation pathways promote low-grade chronic inflammation in several tissues. However, a direct link between IR and NLRP3 inflammasome activation in skeletal muscle has not been reported. Here, we evaluated the NLRP3 inflammasome components and their role in GLUT4 translocation impairment in skeletal muscle during IR. Male C57BL/6J mice were fed with a normal control diet (NCD) or high-fat diet (HFD) for 8 weeks. The protein levels of NLRP3, ASC, caspase-1, gasdermin-D (GSDMD), and interleukin (IL)-1ß were measured in both homogenized and isolated fibers from the flexor digitorum brevis (FDB) or soleus muscle. GLUT4 translocation was determined through GLUT4myc-eGFP electroporation of the FBD muscle. Our results, obtained using immunofluorescence, showed that adult skeletal muscle expresses the inflammasome components. In the FDB and soleus muscles, homogenates from HFD-fed mice, we found increased protein levels of NLRP3 and ASC, higher activation of caspase-1, and elevated IL-1ß in its mature form, compared to NCD-fed mice. Moreover, GSDMD, a protein that mediates IL-1ß secretion, was found to be increased in HFD-fed-mice muscles. Interestingly, MCC950, a specific pharmacological NLRP3 inflammasome inhibitor, promoted GLUT4 translocation in fibers isolated from the FDB muscle of NCD- and HFD-fed mice. In conclusion, we found increased NLRP3 inflammasome components in adult skeletal muscle of obese insulin-resistant animals, which might contribute to the low-grade chronic metabolic inflammation of skeletal muscle and IR development.


Assuntos
Transportador de Glucose Tipo 4/metabolismo , Inflamassomos/metabolismo , Resistência à Insulina/fisiologia , Interleucina-1beta/metabolismo , Músculo Esquelético/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Caspase 1/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Furanos/farmacologia , Indenos/farmacologia , Inflamassomos/química , Interleucina-1beta/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Obesidade/induzido quimicamente , Obesidade/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Sulfonamidas/farmacologia
9.
Molecules ; 26(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068304

RESUMO

Diabetes mellitus (DM) is cited as a serious worldwide health problem that occupies second place in causes of annual mortality in Mexico. Among Mexican flora, nearly 300 plant species have been employed as hypoglycemic in popular use. Thus, their study entertains great relevance In this context, this work contributes a clear and timely review of the plant species utilized in Traditional Mexican Medicine and experimental biological models in which not only have the hypoglycemic properties of the extracts and the isolated compounds been considered, but also the anti-inflammatory and antioxidant properties, taking into account an integral focus based on the complex mechanisms involved in the pathogenesis and physiopathology of DM. Among the species reviewed, we highlight Psacalium decompositum (Asteraceae), due to the potent hypoglycemic, anti-inflammatory, and antioxidant activity of the sesquiterpenes identified as majority compounds isolated from the root, such as cacalol and cacalone that also possess the capacity of increasing insulin levels. In this manner, the present manuscript attempts to contribute necessary information for the future study of bioactive molecules that are useful in the treatment of DM, as well as also being a contribution to the knowledge and diffusion of Mexican Traditional Medicine.


Assuntos
Diabetes Mellitus/terapia , Plantas Medicinais/química , Psacalium/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Modelos Animais de Doenças , Humanos , México
10.
Molecules ; 26(9)2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33923276

RESUMO

Bursera morelensis is used in Mexican folk medicine to treat wounds on the skin. Recently, it was shown that the essential oil (EO) of B. morelensis has wound healing activity, accelerating cutaneous wound closure and generating scars with good tensile strength. α-pinene (PIN) and α-phellandrene (FEL) are terpenes that have been found in this EO, and it has been shown in different studies that both have anti-inflammatory activity. The aim of this study was to determine the wound healing activity of these two terpenes. The results of in vitro tests demonstrate that PIN and FEL are not cytotoxic at low concentrations and that they do not stimulate fibroblast cell proliferation. In vivo tests showed that the terpenes produce stress-resistant scars and accelerate wound contraction, due to collagen deposition from the early stages, in wounds treated with both terpenes. Therefore, we conclude that both α-pinene and α-phellandrene promote the healing process; this confirms the healing activity of the EO of B. morelensis, since having these terpenes as part of its chemical composition explains part of its demonstrated activity.


Assuntos
Monoterpenos Bicíclicos/farmacologia , Monoterpenos Cicloexânicos/farmacologia , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Monoterpenos Bicíclicos/química , Bursera/química , Monoterpenos Cicloexânicos/química , Humanos , México , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Extratos Vegetais/química , Pele/química , Terpenos/química , Terpenos/farmacologia
11.
Molecules ; 25(8)2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32295241

RESUMO

Bursera morelensis is used in Mexican folk medicine to treat wounds on the skin. It is an endemic tree known as "aceitillo", and the antibacterial and antifungal activity of its essential oil has been verified; it also acts as an anti-inflammatory. All of these reported biological activities make the essential oil of B. morelensis a candidate to accelerate the wound-healing process. The objective was to determine the wound-healing properties of B. morelensis' essential oil on a murine model. The essential oil was obtained by hydro-distillation, and the chemical analysis was performed by gas chromatography-mass spectrometry (GC-MS). In the murine model, wound-healing efficacy (WHE) and wound contraction (WC) were evaluated. Cytotoxic activity was evaluated in vitro using peritoneal macrophages from BALB/c mice. The results showed that 18 terpenoid-type compounds were identified in the essential oil. The essential oil had remarkable WHE regardless of the dose and accelerated WC and was not cytotoxic. In vitro tests with fibroblasts showed that cell viability was dose-dependent; by adding 1 mg/mL of essential oil (EO) to the culture medium, cell viability decreased below 80%, while, at doses of 0.1 and 0.01 mg/mL, it remained around 90%; thus, EO did not intervene in fibroblast proliferation, but it did influence fibroblast migration when wound-like was done in monolayer cultures. The results of this study demonstrated that the essential oil was a pro-wound-healing agent because it had good healing effectiveness with scars with good tensile strength and accelerated repair. The probable mechanism of action of the EO of B. morelensis, during the healing process, is the promotion of the migration of fibroblasts to the site of the wound, making them active in the production of collagen and promoting the remodeling of this collagen.


Assuntos
Bursera/química , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Cromatografia Gasosa-Espectrometria de Massas , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Óleos Voláteis/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Óleos de Plantas/química , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia
12.
Pharmacol Res ; 146: 104273, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31096010

RESUMO

Growth differentiation factor 11 (GDF11) is a novel factor with controversial effects on cardiac hypertrophy both in vivo and in vitro. Although recent evidence has corroborated that GDF11 prevents the development of cardiac hypertrophy, its molecular mechanism remains unclear. In our previous work, we showed that norepinephrine (NE), a physiological pro-hypertrophic agent, increases cytoplasmic Ca2+ levels accompanied by a loss of physical and functional communication between sarcoplasmic reticulum (SR) and mitochondria, with a subsequent reduction in the mitochondrial Ca2+ uptake and mitochondrial metabolism. In order to study the anti-hypertrophic mechanism of GDF11, our aim was to investigate whether GDF11 prevents the loss of SR-mitochondria communication triggered by NE. Our results show that: a) GDF11 prevents hypertrophy in cultured neonatal rat ventricular myocytes treated with NE. b) GDF11 attenuates the NE-induced loss of contact sites between both organelles. c) GDF11 increases oxidative mitochondrial metabolism by stimulating mitochondrial Ca2+ uptake. In conclusion, the GDF11-dependent maintenance of physical and functional communication between SR and mitochondria is critical to allow Ca2+ transfer between both organelles and energy metabolism in the cardiomyocyte and to avoid the activation of Ca2+-dependent pro-hypertrophic signaling pathways.


Assuntos
Cardiomegalia/metabolismo , Fatores de Diferenciação de Crescimento/metabolismo , Mitocôndrias Cardíacas/fisiologia , Miócitos Cardíacos/metabolismo , Retículo Sarcoplasmático/fisiologia , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Cardiomegalia/induzido quimicamente , Comunicação Celular , Metabolismo Energético , Mitocôndrias Cardíacas/metabolismo , Ratos Sprague-Dawley
13.
Int J Mol Sci ; 19(5)2018 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-29783655

RESUMO

Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-ß family, has been shown to act as a negative regulator in cardiac hypertrophy. Ca2+ signaling modulates cardiomyocyte growth; however, the role of Ca2+-dependent mechanisms in mediating the effects of GDF11 remains elusive. Here, we found that GDF11 induced intracellular Ca2+ increases in neonatal rat cardiomyocytes and that this response was blocked by chelating the intracellular Ca2+ with BAPTA-AM or by pretreatment with inhibitors of the inositol 1,4,5-trisphosphate (IP3) pathway. Moreover, GDF11 increased the phosphorylation levels and luciferase activity of Smad2/3 in a concentration-dependent manner, and the inhibition of IP3-dependent Ca2+ release abolished GDF11-induced Smad2/3 activity. To assess whether GDF11 exerted antihypertrophic effects by modulating Ca2+ signaling, cardiomyocytes were exposed to hypertrophic agents (100 nM testosterone or 50 µM phenylephrine) for 24 h. Both treatments increased cardiomyocyte size and [³H]-leucine incorporation, and these responses were significantly blunted by pretreatment with GDF11 over 24 h. Moreover, downregulation of Smad2 and Smad3 with siRNA was accompanied by inhibition of the antihypertrophic effects of GDF11. These results suggest that GDF11 modulates Ca2+ signaling and the Smad2/3 pathway to prevent cardiomyocyte hypertrophy.


Assuntos
Sinalização do Cálcio , Cardiomegalia/metabolismo , Fatores de Diferenciação de Crescimento/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Cálcio/metabolismo , Células Cultivadas , Fatores de Diferenciação de Crescimento/genética , Miócitos Cardíacos/efeitos dos fármacos , Fenilefrina/farmacologia , Ratos , Ratos Sprague-Dawley , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Testosterona/farmacologia
14.
Molecules ; 23(10)2018 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-30304821

RESUMO

Quercetagetin and patuletin were extracted by the same method from two different Tagetes species that have multiple uses in folk medicine in Mexico and around the globe, one of which is as an anticancer agent. Their biological activity (IC50 and necrotic, apoptotic and selective activities of these flavonols) was evaluated and compared to that of quercetin, examining specifically the effects of C6 substitution among quercetin, quercetagetin and patuletin. We find that the presence of a methoxyl group in C6 enhances their potency.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Cromonas/química , Cromonas/farmacologia , Flavonas/química , Flavonas/farmacologia , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular
15.
Molecules ; 23(12)2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30572603

RESUMO

Cacalolides are a kind of sesquiterpenoids natural compounds synthesized by Psacalium decompositum (A. Gray) H. Rob. & Brettell or Psacalium peltatum (Kunth) Cass. Antioxidant and hypoglycemic effects have been found for cacalolides such as cacalol, cacalone or maturine, however, their effects on inflammatory processes are still largely unclear. The main aim of this study was to investigate the biological activities of secondary metabolites from P. decompositum and P. peltatum through two approaches: (1) chemoinformatic and toxicoinformatic analysis based on ethnopharmacologic background; and (2) the evaluation of their potential anti-inflammatory/anti-allergic effects in bone marrow-derived mast cells by IgE/antigen complexes. The bioinformatics properties of the compounds: cacalol; cacalone; cacalol acetate and maturin acetate were evaluated through Osiris DataWarrior software and Molinspiration and PROTOX server. In vitro studies were performed to test the ability of these four compounds to inhibit antigen-dependent degranulation and intracellular calcium mobilization, as well as the production of reactive oxygen species in bone marrow-derived mast cells. Our findings showed that cacalol displayed better bioinformatics properties, also exhibited a potent inhibitory activity on IgE/antigen-dependent degranulation and significantly reduced the intracellular calcium mobilization on mast cells. These data suggested that cacalol could reduce the negative effects of the mast cell-dependent inflammatory process.


Assuntos
Mastócitos/metabolismo , Psacalium/química , Receptores de IgE/metabolismo , Animais , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Inflamação/metabolismo , Masculino , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/metabolismo , Sesquiterpenos/farmacologia
16.
Molecules ; 22(12)2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29206158

RESUMO

The candidiasis caused by C. albicans is a public health problem. The abuse of antifungals has contributed to the development of resistance. B. morelensis has demonstrated antibacterial and antifungal activities. In this work the activity of the essential oil of B. morelensis was evaluated and for its two pure compounds with analysis of the different mechanisms of pathogenesis important for C. albicans. The essential oil was obtained by the hydro-distillation method and analyzed using GC-MS. The anti-Candida activity was compared between to essential oil, α-Pinene and γ-Terpinene. GC-MS of the essential oil demonstrated the presence of 13 compounds. The essential oil showed antifungal activity against four C. albicans strains. The most sensitive strain was C. albicans 14065 (MFC 2.0 mg/mL and MIC50 0.125 mg/mL) with α-Pinene and γ-Terpinene having MFCs of 4.0 and 16.0 mg/mL respectively. The essential oil inhibited the growth of the germ tube in 87.94% (8.0 mg/mL). Furthermore, it was observed that the essential oil diminishes the transcription of the gene INT1. This work provides evidence that confirms the anti-Candida activity of the B. morelensis essential oil and its effect on the growth of the germ tube and transcription of the gene INT1.


Assuntos
Antifúngicos/farmacologia , Bursera/química , Candida/efeitos dos fármacos , Monoterpenos/farmacologia , Esporos Fúngicos/efeitos dos fármacos , Antifúngicos/química , Antifúngicos/isolamento & purificação , Monoterpenos Bicíclicos , Candida/genética , Candida/crescimento & desenvolvimento , Candida/metabolismo , Moléculas de Adesão Celular/antagonistas & inibidores , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Monoterpenos Cicloexânicos , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Expressão Gênica , Testes de Sensibilidade Microbiana , Monoterpenos/isolamento & purificação , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Extratos Vegetais/química , Óleos de Plantas/química , Óleos de Plantas/isolamento & purificação , Óleos de Plantas/farmacologia , Esporos Fúngicos/genética , Esporos Fúngicos/crescimento & desenvolvimento , Esporos Fúngicos/metabolismo
17.
Pharm Biol ; 55(1): 1787-1791, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28524742

RESUMO

CONTEXT: Piqueria trinervia Cav. (Asteraceae) is a plant species with a long history in traditional medicine to cure diarrhoea and other digestive disorders. OBJECTIVE: The study investigates the antigiardial activity of piquerol, trinervinol, red oil and two fractions (F1 and F2) from P. trinervia. MATERIALS AND METHODS: P. trinervia was collected in the Ajusco in Mexico City. Aerial parts were ground and mixed with water to obtain the extract, which was treated with dichloromethane to isolate piquerol and trinervinol (P & T). Remnants were the red oil, fractions 1 and 2 (RO, F1 & F2). Trophozoites of Giardia intestinalis were treated with P, T, RO, F1 and F2 at different concentrations (0.78-200 µg/mL) for 48 h. Antigiardial activity was measured using the methylene blue reduction, and the cytotoxicity assayed on human fibroblasts and Vero cells by reduction of tetrazolium salts. RESULTS: Trinervinol and piquerol showed antigiardial activity with an IC50 = 2.03 and 2.42 µg/mL, and IC90 = 13.03 and 8.74 µg/mL, respectively. The concentrations of trinervinol (CC50 = 590 µg/mL) and piquerol (CC50 = 501 µg/mL) were not cytotoxic to human fibroblasts. CONCLUSIONS: Compounds from P. trinervia showed antigiardial activity; to enhance this activity, piquerol and trinervinol can be chemically modified.


Assuntos
Antiprotozoários/farmacologia , Asteraceae/química , Giardia lamblia/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Antiprotozoários/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Giardia lamblia/crescimento & desenvolvimento , Concentração Inibidora 50 , Cloreto de Metileno/química , México , Testes de Sensibilidade Parasitária , Fitoterapia , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Plantas Medicinais , Solventes/química , Terpenos/isolamento & purificação , Terpenos/farmacologia , Células Vero
18.
Saudi Pharm J ; 25(8): 1137-1143, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30166901

RESUMO

Cancer is the major cause of death in the world, representing a significant public health problem. Plants have been shown as a great source of secondary metabolites with anticancer activity. The aim of this work was evaluated the antiproliferative activity of the methanolic extracts, chemical fractions and the compound spinasterol isolated of medicinal plant Stegnosperma halimifolium. The methanolic extracts of stem, leaf and stem/leaf was obtained by maceration. The methanolic extract of stem was purified by successive extractions with solvents as n-hexane, ethyl acetate and ethanol. The n-hexane fraction was separated by column chromatographic and monitored by thin layer chromatographic. The compound spinasterol was characterized by 1H NMR, 13C NMR and Mass Spectrometry. Methanolic extracts, chemical, chromatographic fractions and spinasterol was evaluated against RAW 264.7, M12.C3.F6, PC-3, LS-180, A549 and HeLa cancer cell lines by the standardized method MTT for determinate the antiproliferative activity. Methanolic extract of stem shown the better antiproliferative activity against the murine macrophage cancer cell line RAW 264.7. n-Hexane chemical fraction shown antiproliferative activity against human alveolar cancer cell line A549 and RAW 264.7. Was isolated and characterized a compound by NMR 1H and 13C, revealing the presence of sterol spinasterol. Spinasterol shown to have antiproliferative activity against cervical cancer cell line HeLa and RAW 264.7, indicating that spinasterol can be a responsible compound of antiproliferative activity found in the methanolic extract of Stegnosperma halimifolium.

19.
Molecules ; 21(11)2016 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-27869734

RESUMO

The molecular hosts cyclodextrins form inclusion complexes with a wide variety of guests, resulting in complexes with various host:guest stoichiometries. In the case of a series of 19 1,4-naphthoquinolines as guests with either ß- or γ-cyclodextrin studied using electrospray mass spectroscopy, in most cases only 1:1 complexes were observed, with 2:1 host:guest complexes observed in just 6 out of 38 host:guest combinations. It is shown that these higher-order complexes were observed only in the case of small (or no) electronically withdrawing substituents, and were much less likely in the case of the larger γ-cyclodextrin host. The size and electronic properties of the substituents involved shows that both steric and electronic factors must be taken into account in predicting which cyclodextrin host:guest stoichiometries will be stable enough to form (or once formed, be robust enough to be observed in the ESI-MS experiments). It is clear that the prediction of host-guest stoichiometry for a specific host-guest pair is complicated, and involves a subtle interplay of both electronic and steric factors. However, there are definite trends, which can be used to help predict host:guest stoichiometry for a given host-guest pair.


Assuntos
Naftoquinonas/química , beta-Ciclodextrinas/química , gama-Ciclodextrinas/química , Modelos Moleculares , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray/métodos
20.
Pharm Biol ; 54(9): 1822-30, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26731099

RESUMO

Context Hamelia patens Jacq. (Rubiaceae) is traditionally used to treat wounds, inflammation and diabetes. However, there is still a lack of scientific evidence to support these applications. Objective The objective of this study is to evaluate the anti-inflammatory, antioxidant and antidiabetic activities of Hamelia patens, and identify its bioactive compounds. Materials and methods Four extracts were obtained by maceration and liquid-liquid extraction: HEX, DCM-EtOAc, MeOH-EtOAc and MeOH-Aq. The anti-inflammatory effect was evaluated orally on rat paw carrageenan-induced oedema over 6 h (50, 200 and 500 mg/kg), and topically in mouse ear oedema induced by 12-tetradecanoylphorbol-13-acetate (TPA) after 4 h (0.5 and 1 mg/ear). We also evaluated myeloperoxidase levels in ear tissue, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging ability, and in vitro α-glucosidase inhibition. The chemical compounds were separated by column chromatography and identified by spectroscopic analysis. Results We found that the oral administration of the HEX extract at 500 and 200 mg/kg significantly decreased the carrageenan-induced inflammation after 1 and 3 h, respectively. The MeOH-EtOAc extract significantly inhibited myeloperoxidase activity (83.5%), followed by the DCM-EtOAc extract (76%), ß-sitosterol/stigmasterol (72.7%) and the HEX extract (55%), which significantly decreased oedema induced by TPA at both doses, giving a similar effect to indomethacin. We also found that the MeOH-EtOAc, MeOH-Aq and DCM-EtOAc extracts showed good DPPH scavenging activity (IC50 values of 18.6, 93.9 and 158.2 µg/mL, respectively). The HEX extract showed the lowest α-glucosidase inhibition (an IC50 value of 26.07 µg/mL), followed by the MeOH-EtOAc extract (an IC50 value of 30.18 µg/mL), ß-sitosterol/stigmasterol (IC50 34.6 µg/mL) and compound A ((6E,10E,14E,18E)-2,6,10,14,18,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene, an IC50 value of 114.6 µg/mL), which were isolated for the first time from Hamelia patens. Discussion and conclusion Hamelia patens possesses anti-inflammatory, antioxidant and α-glucosidase inhibitory activities, which support its traditional use. These effects can be attributed to the identified compounds.


Assuntos
Anti-Inflamatórios/farmacologia , Edema/prevenção & controle , Sequestradores de Radicais Livres/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Hamelia , Animais , Anti-Inflamatórios/isolamento & purificação , Compostos de Bifenilo/química , Carragenina , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/metabolismo , Feminino , Sequestradores de Radicais Livres/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Hamelia/química , Peroxidase/metabolismo , Fitoterapia , Picratos/química , Folhas de Planta , Plantas Medicinais , Ratos Wistar , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Proteínas de Saccharomyces cerevisiae/metabolismo , Solventes/química , Acetato de Tetradecanoilforbol , Fatores de Tempo , alfa-Glucosidases/metabolismo
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