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1.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360706

RESUMO

For the treatment of severe COVID-19, supplementation with human plasma-purified α-1 antitrypsin (AAT) to patients is currently considered. AAT inhibits host proteases that facilitate viral entry and possesses broad anti-inflammatory and immunomodulatory activities. Researchers have demonstrated that an interaction between SARS-CoV-2 spike protein (S) and lipopolysaccharides (LPS) enhances pro-inflammatory responses in vitro and in vivo. Hence, we wanted to understand the potential anti-inflammatory activities of plasma-derived and recombinant AAT (recAAT) in a model of human total peripheral blood mononuclear cells (PBMCs) exposed to a combination of CHO expressed trimeric spike protein and LPS, ex vivo. We confirmed that cytokine production was enhanced in PBMCs within six hours when low levels of LPS were combined with purified spike proteins ("spike"). In the presence of 0.5 mg/mL recAAT, however, LPS/spike-induced TNF-α and IL-1ß mRNA expression and protein release were significantly inhibited (by about 46-50%) relative to LPS/spike alone. Although without statistical significance, recAAT also reduced production of IL-6 and IL-8. Notably, under the same experimental conditions, the plasma-derived AAT preparation Respreeza (used in native and oxidized forms) did not show significant effects. Our findings imply that an early pro-inflammatory activation of human PBMCs is better controlled by the recombinant version of AAT than the human plasma-derived AAT used here. Considering the increasing clinical interest in AAT therapy as useful to ameliorate the hyper-inflammation seen during COVID-19 infection, different AAT preparations require careful evaluation.


Assuntos
Anti-Inflamatórios/farmacologia , Leucócitos Mononucleares/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , alfa 1-Antitripsina/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/imunologia , Células CHO , COVID-19/terapia , Células Cultivadas , Cricetulus , Citocinas/metabolismo , Humanos , Inflamação/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/toxicidade , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , alfa 1-Antitripsina/química , alfa 1-Antitripsina/imunologia
2.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360732

RESUMO

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes encoding antioxidant and detoxifying enzymes, Nrf2 is also implicated in a wide network regulating anti-inflammatory response and metabolic reprogramming. Such a broad spectrum of actions renders the factor a key regulator of cell fate and a strategic player in the control of cell transformation and response to viral infections. The Nrf2 protective roles in normal cells account for its anti-tumour and anti-viral functions. However, Nrf2 overstimulation often occurs in tumour cells and a complex correlation of Nrf2 with cancer initiation and progression has been widely described. Therefore, if on one hand, Nrf2 has a dual role in cancer, on the other hand, the factor seems to display a univocal function in preventing inflammation and cytokine storm that occur under viral infections, specifically in coronavirus disease 19 (COVID-19). In such a variegate context, the present review aims to dissect the roles of Nrf2 in both cancer and COVID-19, two widespread diseases that represent a cause of major concern today. In particular, the review describes the molecular aspects of Nrf2 signalling in both pathological situations and the most recent findings about the advantages of Nrf2 inhibition or activation as possible strategies for cancer and COVID-19 treatment respectively.


Assuntos
COVID-19/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias/metabolismo , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , COVID-19/tratamento farmacológico , Humanos , Fator 2 Relacionado a NF-E2/química , Neoplasias/tratamento farmacológico , Transdução de Sinais
3.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445513

RESUMO

The activation of signal transducer and activator of transcription 3 (STAT3), as well as up-regulation of cytokines and growth factors to promote STAT3 activation, have been found in the epidermis of psoriatic lesions. Recently, a series of synthetic compounds possessing the Michael acceptor have been reported as STAT3 inhibitors by covalently binding to cysteine of STAT3. We synthesized a Michael acceptor analog, SKSI-0412, and confirmed the binding affinity between STAT3 and SKSI-0412. We hypothesized that the SKSI-0412 can inhibit interleukin (IL)-17A-induced inflammation in keratinocytes. The introduction of IL-17A increased the phosphorylation of STAT3 in keratinocytes, whereas the inactivation of STAT3 by SKSI-0412 reduced IL-17A-induced STAT3 phosphorylation and IκBζ expression. In addition, human ß defensin-2 and S100A7, which are regulated by IκBζ, were significantly decreased with SKSI-0412 administration. We also confirmed that SKSI-0412 regulates cell proliferation, which is the major phenotype of psoriasis. Based on these results, we suggest targeting STAT3 with SKSI-0412 as a novel therapeutic strategy to regulate IL-17A-induced psoriatic inflammation in keratinocytes.


Assuntos
Anti-Inflamatórios/farmacologia , Interleucina-17/efeitos adversos , Queratinócitos/citologia , Fator de Transcrição STAT3/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Regulação para Baixo , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Fosforilação/efeitos dos fármacos , Cultura Primária de Células , Fator de Transcrição STAT3/química , Transdução de Sinais/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química
4.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361744

RESUMO

Korean red pine (Pinus densiflora) belongs to the Genus Pinus, and its bark contains a great amount of naturally occurring phenolic compounds. Until now, few studies have been conducted to assess the neuroprotective effects of Pinus densiflora bark extract against brain ischemic injury. The aim of this study was to investigate the neuroprotective effects of pre-treatment with the extract in the hippocampus following 5-min transient forebrain ischemia in gerbils. Furthermore, this study examined the anti-inflammatory effect as a neuroprotective mechanism of the extract. Pinus densiflora bark was extracted by pure water (100 °C), and this extract was quantitatively analyzed and contained abundant polyphenols, flavonoids, and proanthocyanidins. The extract (25, 50, and 100 mg/kg) was orally administered once a day for seven days before the ischemia. In the gerbil hippocampus, death of the pyramidal neurons was found in the subfield cornu ammonis 1 (CA1) five days after the ischemia. This death was significantly attenuated by pre-treatment with 100 mg/kg, not 25 or 50 mg/kg, of the extract. The treatment with 100 mg/kg of the extract markedly inhibited the activation of microglia (microgliosis) and significantly decreased the expression of pro-inflammatory cytokines (interleukin 1ß and tumor necrosis factor α). In addition, the treatment significantly increased anti-inflammatory cytokines (interleukin 4 and interleukin 13). Taken together, this study clearly indicates that pre-treatment with 100 mg/kg of Pinus densiflora bark extract in gerbils can exert neuroprotection against brain ischemic injury by the attenuation of neuroinflammatory responses.


Assuntos
Anti-Inflamatórios/farmacologia , Isquemia Encefálica/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Pinus/química , Prosencéfalo/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Flavonoides/química , Flavonoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Gerbillinae , Hipocampo/metabolismo , Hipocampo/patologia , Inflamação , Interleucina-13/agonistas , Interleucina-13/genética , Interleucina-13/metabolismo , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-4/agonistas , Interleucina-4/genética , Interleucina-4/metabolismo , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Fármacos Neuroprotetores/química , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Proantocianidinas/química , Proantocianidinas/farmacologia , Prosencéfalo/metabolismo , Prosencéfalo/patologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Células Piramidais/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
5.
Chem Pharm Bull (Tokyo) ; 69(8): 811-816, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34334527

RESUMO

Three new aconitine-type C19-diterpenoid alkaloid namely novolunines A (1), B (2), and C (3), along with fifteen known diterpenoid alkaloids were isolated from the roots of Aconitum novoluridum, whose phytochemical investigations have never been reported before. The structures of three new alkaloids were established on the basis of spectra data (high-resolution electrospray ionization (HR-ESI)-MS, IR, one dimensional (1D)- and 2D-NMR). Noteworthily, novolunines A (1) and B (2) are two diterpenoid alkaloids bearing conformational isomerism. In addition, the diterpenoid alkaloids 1-3 did not show any anti-acetylcholinesterase (AChE) or anti-inflammatory activities.


Assuntos
Acetilcolinesterase/metabolismo , Aconitum/química , Anti-Inflamatórios/farmacologia , Inibidores da Colinesterase/farmacologia , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Electrophorus , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7
6.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361797

RESUMO

Carpesium divaricatum Sieb. & Zucc., a traditional medicinal plant used as an inflammation-relieving remedy, is a rich source of terpenoids. At least 40 germacrane-type sesquiterpene lactones, representatives of four different structural groups, were isolated from the plant. Cytotoxicity against cancer cells in vitro is the most frequently described biological activity of the compounds. However, little is known about the selectivity of the cytotoxic effect. The anti-inflammatory activity of the germacranolides is also poorly documented. The objective of the present study was to assess the cytotoxic activity of selected C. divaricatum germacranolides-derivatives of 4,5,8,9-tetrahydroxy-3-oxo-germacran-6,12-olide towards cancer and normal cell lines (including cells of different p53 status). Moreover, to assess the anti-inflammatory effect of the compounds, the release of four proinflammatory cytokines/chemokines (IL-1ß, IL-8, TNF-α and CCL2) by lipopolysaccharide-stimulated human neutrophils was measured by ELISA. The investigated sesquiterpene lactones demonstrated nonselective activity towards prostate cancer (Du145 and PC3) and normal prostate epithelial cells (PNT2) as well as against melanoma cells (A375 and HTB140) and keratinocytes (HaCaT). Cytotoxic activity against osteosarcoma cells was independent of their p53 status. In sub-cytotoxic concentrations (0.5-2.5 µM) the studied compounds significantly decreased cytokine/chemokine release by lipopolysaccharide-stimulated human leukocytes.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Asteraceae/química , Citotoxinas/farmacologia , Sesquiterpenos de Germacrano/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/classificação , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/classificação , Antineoplásicos Fitogênicos/isolamento & purificação , Asteraceae/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CCL2/genética , Quimiocina CCL2/imunologia , Citotoxinas/química , Citotoxinas/classificação , Citotoxinas/isolamento & purificação , Doxorrubicina/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Concentração Inibidora 50 , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Extratos Vegetais/química , Plantas Medicinais , Polônia , Cultura Primária de Células , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/classificação , Sesquiterpenos de Germacrano/isolamento & purificação , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/imunologia
7.
Molecules ; 26(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34361560

RESUMO

The extracts of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) have various therapeutic effects, including inflammation and allergy. In this study, gomisin M2 (GM2) was isolated from S. chinensis and its beneficial effects were assessed against atopic dermatitis (AD). We evaluated the therapeutic effects of GM2 on 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced AD-like skin lesions with BALB/c mice ears and within the tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated keratinocytes. The oral administration of GM2 resulted in reduced epidermal and dermal thickness, infiltration of tissue eosinophils, mast cells, and helper T cells in AD-like lesions. GM2 suppressed the expression of IL-1ß, IL-4, IL-5, IL-6, IL-12a, and TSLP in ear tissue and the expression of IFN-γ, IL-4, and IL-17A in auricular lymph nodes. GM2 also inhibited STAT1 and NF-κB phosphorylation in DNCB/DFE-induced AD-like lesions. The oral administration of GM2 reduced levels of IgE (DFE-specific and total) and IgG2a in the mice sera, as well as protein levels of IL-4, IL-6, and TSLP in ear tissues. In TNF-α/IFN-γ-stimulated keratinocytes, GM2 significantly inhibited IL-1ß, IL-6, CXCL8, and CCL22 through the suppression of STAT1 phosphorylation and the nuclear translocation of NF-κB. Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.


Assuntos
Anti-Inflamatórios/farmacologia , Ciclo-Octanos/farmacologia , Dermatite Atópica , Dermatophagoides farinae/imunologia , Derme/imunologia , Dinitroclorobenzeno/toxicidade , Epiderme/imunologia , NF-kappa B/imunologia , Fator de Transcrição STAT1/imunologia , Animais , Anti-Inflamatórios/química , Ciclo-Octanos/química , Citocinas/imunologia , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/imunologia , Camundongos , Camundongos Endogâmicos BALB C
8.
Molecules ; 26(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34443416

RESUMO

Acylhydrazones are still an important framework to the design of new bioactive compounds. As treatment of chronic pain represents a clinical challenge, we decided to modify the structure of LASSBio-1514 (1), previously described as anti-inflammatory and analgesic prototype. Applying the homologation as a strategy for molecular modification, we designed a series of cyclopentyl- (2a-e), cyclobutyl- (3a-e), and cyclopropylacylhydrazones (4a-e) that were synthetized and evaluated in murine models of inflammation and pain. A comparison of their in silico physicochemical and drug-like profile was conducted, as well as their anti-inflammatory and analgesic effect. Compounds 4a (LASSBio-1755) and 4e (LASSBio-1757) displayed excellent in silico drug-like profiles and were identified as new analgesic lead-candidates in acute and chronic model of pain, through oral administration.


Assuntos
Simulação por Computador , Desenho de Fármacos , Hidrazonas/síntese química , Hidrazonas/farmacologia , Preparações Farmacêuticas/síntese química , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Aspirina/farmacologia , Células CACO-2 , Humanos , Hidrazonas/química , Hiperalgesia/patologia , Indometacina/farmacologia , Masculino , Camundongos , Conformação Molecular , Peso Molecular , Preparações Farmacêuticas/química , Ratos Wistar
9.
Molecules ; 26(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34443495

RESUMO

Phytochemical investigation and chromatographic separation of extracts from the actinobacteria strain Saccharomonospora piscinae that was isolated from dried fishpond sediment of Kouhu township, in the south of Taiwan, led to the isolation of three new compounds, saccharpiscinols A-C (1-3, respectively), and three new natural products, namely (2S)-5,7,3',4'-tetrahydroxy-6,8-dimethylflavanone (4), methyl-4-hydroxy-2-methoxy-6-methylbenzoate (5), and (±)-7-acetyl-4,8-dihydroxy-6-methyl-1-tetralone (6). Compounds 4-6 were reported before as synthesized products, herein, they are reported from nature for the first time. The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Saccharpiscinol A showed inhibitory activities against LPS-induced NO production.


Assuntos
Actinobacteria/química , Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Animais , Anti-Inflamatórios/química , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Misturas Complexas , Flavonoides/química , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Células RAW 264.7
10.
Molecules ; 26(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34361609

RESUMO

The use of copaiba oil has been reported since the 16th century in Amazon traditional medicine, especially as an anti-inflammatory ingredient and for wound healing. The use of copaiba oil continues today, and it is sold in various parts of the world, including the United States. Copaiba oil contains mainly sesquiterpenes, bioactive compounds that are popular for their positive effect on human health. As part of our ongoing research endeavors to identify the chemical constituents of broadly consumed herbal supplements or their adulterants, copaiba oil was investigated. In this regard, copaiba oil was subjected to repeated silica gel column chromatography to purify the compounds. As a result, one new and seven known sesquiterpenes/sesquiterpenoids were isolated and identified from the copaiba oil. The new compound was elucidated as (E)-2,6,10-trimethyldodec-8-en-2-ol. Structure elucidation was achieved by 1D- and 2D NMR and GC/Q-ToF mass spectral data analyses. The isolated chemical constituents in this study could be used as chemical markers to evaluate the safety or quality of copaiba oil.


Assuntos
Anti-Inflamatórios/química , Fabaceae/química , Óleos Voláteis/química , Óleos Vegetais/química , Sesquiterpenos/análise , Humanos , Medicina Tradicional
11.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361701

RESUMO

Arthritis is a chronic inflammatory disease accompanied by pathological reactions such as swelling, redness, fever, and pain in various joint areas. The drugs currently available to treat arthritis are associated with diverse side-effects. Therefore, there is a need for safer and more effective treatments to alleviate the inflammation of arthritis with fewer side-effects. In this study, a new sterol, Δ8(14)-ergostenol, was discovered, and its glycosides were synthesized and found to be more efficient in terms of synthesis or anti-inflammatory activity than either spinasterol or 5,6-dihydroergosterol is. Among these synthetic glycosides, galactosyl ergostenol inhibited the expression of inflammatory mediators in TNF-α-stimulated FLS and TNF-α-induced MMPs and collagen type II A1 degradation in human chondrocytes. These results suggest the new galactosyl ergostenol as a treatment candidate for arthritis.


Assuntos
Anti-Inflamatórios/farmacologia , Condrócitos/efeitos dos fármacos , Ergosterol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glicosídeos/farmacologia , Sinoviócitos/efeitos dos fármacos , Anti-Inflamatórios/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Ergosterol/química , Glicosídeos/síntese química , Humanos , Inflamação/prevenção & controle , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Modelos Biológicos , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Transdução de Sinais , Sinoviócitos/citologia , Sinoviócitos/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/farmacologia
12.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361704

RESUMO

Significant growth of interest in cannabis (Cannabis sativa L.), especially its natural anti-inflammatory and antioxidative properties, has been observed recently. This narrative review aimed to present the state of the art of research concerning the anti-inflammatory activity of all classes of cannabinoids published in the last five years. Multimodal properties of cannabinoids include their involvement in immunological processes, anti-inflammatory, and antioxidative effects. Cannabinoids and non-cannabinoid compounds of cannabis proved their anti-inflammatory effects in numerous animal models. The research in humans is missing, and the results are unconvincing. Although preclinical evidence suggests cannabinoids are of value in treating chronic inflammatory diseases, the clinical evidence is scarce, and further well-designed clinical trials are essential to determine the prospects for using cannabinoids in inflammatory conditions.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Canabinoides/uso terapêutico , Cannabis/química , Analgésicos/química , Analgésicos/classificação , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/classificação , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/química , Antioxidantes/classificação , Antioxidantes/isolamento & purificação , Canabinoides/química , Canabinoides/classificação , Canabinoides/isolamento & purificação , Humanos , Inflamação/prevenção & controle , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Relação Estrutura-Atividade
13.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361712

RESUMO

The genus Maytenus is a member of the Celastraceae family, of which several species have long been used in traditional medicine. Between 1976 and 2021, nearly 270 new compounds have been isolated and elucidated from the genus Maytenus. Among these, maytansine and its homologues are extremely rare in nature. Owing to its unique skeleton and remarkable bioactivities, maytansine has attracted many synthetic endeavors in order to construct its core structure. In this paper, the current status of the past 45 years of research on Maytenus, with respect to its chemical and biological activities are discussed. The chemical research includes its structural classification into triterpenoids, sesquiterpenes and alkaloids, along with several chemical synthesis methods of maytansine or maytansine fragments. The biological activity research includes activities, such as anti-tumor, anti-bacterial and anti-inflammatory activities, as well as HIV inhibition, which can provide a theoretical basis for the better development and utilization of the Maytenus.


Assuntos
Alcaloides/química , Maitansina/análogos & derivados , Maytenus/química , Compostos Fitoquímicos/química , Sesquiterpenos/química , Triterpenos/química , Alcaloides/classificação , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Humanos , Maitansina/isolamento & purificação , Maitansina/farmacologia , Maytenus/metabolismo , Estrutura Molecular , Compostos Fitoquímicos/classificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Plantas Medicinais , Sesquiterpenos/classificação , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Relação Estrutura-Atividade , Triterpenos/classificação , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
14.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361723

RESUMO

Genito-urinary tract infections have a high incidence in the general population, being more prevalent among women than men. These diseases are usually treated with antibiotics, but very frequently, they are recurrent and lead to the creation of resistance and are associated with increased morbidity and mortality. For this reason, it is necessary to develop new compounds for their treatment. In this work, our objective is to review the characteristics of the compounds of a new formulation called Itxasol© that is prescribed as an adjuvant for the treatment of UTIs and composed of ß-arbutin, umbelliferon and n-acetyl cysteine. This formulation, based on biomimetic principles, makes Itxasol© a broad-spectrum antibiotic with bactericidal, bacteriostatic and antifungal properties that is capable of destroying the biofilm and stopping its formation. It also acts as an anti-inflammatory agent, without the adverse effects associated with the recurrent use of antibiotics that leads to renal nephrotoxicity and other side effects. All these characteristics make Itxasol© an ideal candidate for the treatment of UTIs since it behaves like an antibiotic and with better characteristics than other adjuvants, such as D-mannose and cranberry extracts.


Assuntos
Acetilcisteína/uso terapêutico , Arbutina/uso terapêutico , Produtos Biológicos/uso terapêutico , Umbeliferonas/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Acetilcisteína/química , Antibacterianos/química , Antibacterianos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antifúngicos/química , Antifúngicos/uso terapêutico , Arbutina/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Produtos Biológicos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/uso terapêutico , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Candida/patogenicidade , Combinação de Medicamentos , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Bactérias Gram-Positivas/patogenicidade , Humanos , Masculino , Testes de Sensibilidade Microbiana , Umbeliferonas/química , Infecções Urinárias/microbiologia , Infecções Urinárias/patologia
15.
Biomolecules ; 11(7)2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34356599

RESUMO

Artemisia annua L. (AA) has shown for many centuries important therapeutic virtues associated with the presence of artemisinin (ART). The aim of this study was to identify and quantify ART and other secondary metabolites in ethanolic extracts of AA and evaluate the biological activity in the presence of an inflammatory stimulus. In this work, after the extraction of the aerial parts of AA with different concentrations of ethanol, ART was quantified by HPLC and HPLC-MS. In addition, anthocyanins, flavanols, flavanones, flavonols, lignans, low-molecular-weight phenolics, phenolic acids, stilbenes, and terpenes were identified and semi-quantitatively determined by UHPLC-QTOF-MS untargeted metabolomics. Finally, the viability of human neuroblastoma cells (SH-SY5Y) was evaluated in the presence of the different ethanolic extracts and in the presence of lipopolysaccharide (LPS). The results show that ART is more concentrated in AA samples extracted with 90% ethanol. Regarding the other metabolites, only the anthocyanins are more concentrated in the samples extracted with 90% ethanol. Finally, ART and all AA samples showed a protective action towards the pro-inflammatory stimulus of LPS. In particular, the anti-inflammatory effect of the leaf extract of AA with 90% ethanol was also confirmed at the molecular level since a reduction in TNF-α mRNA gene expression was observed in SH-SY5Y treated with LPS.


Assuntos
Anti-Inflamatórios , Artemisia annua/química , Etanol/química , Compostos Fitoquímicos , Extratos Vegetais/química , Folhas de Planta/química , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Linhagem Celular Tumoral , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
16.
Molecules ; 26(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34361576

RESUMO

Prunus mahaleb L. fruit has long been used in the production of traditional liqueurs. The fruit also displayed scavenging and reducing activity, in vitro. The present study focused on unravelling peripheral and central protective effects, antimicrobial but also anti-COVID-19 properties exerted by the water extract of P. mahaleb. Anti-inflammatory effects were studied in isolated mouse colons exposed to lipopolysaccharide. Neuroprotection, measured as a blunting effect on hydrogen-peroxide-induced dopamine turnover, was investigated in hypothalamic HypoE22 cells. Antimicrobial effects were tested against different Gram+ and Gram- bacterial strains. Whereas anti-COVID-19 activity was studied in lung adenocarcinoma H1299 cells, where the gene expression of ACE2 and TMPRSS2 was measured after extract treatment. The bacteriostatic effects induced on Gram+ and Gram- strains, together with the inhibition of COX-2, TNFα, HIF1α, and VEGFA in the colon, suggest the potential of P. mahaleb water extract in contrasting the clinical symptoms related to ulcerative colitis. The inhibition of the hydrogen peroxide-induced DOPAC/DA ratio indicates promising neuroprotective effects. Finally, the downregulation of the gene expression of ACE2 and TMPRSS2 in H1299 cells, suggests the potential to inhibit SARS-CoV-2 virus entry in the human host. Overall, the results support the valorization of the local cultivation of P. mahaleb.


Assuntos
Bactérias/efeitos dos fármacos , Colo/efeitos dos fármacos , Neuroproteção , Extratos Vegetais/farmacologia , SARS-CoV-2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antivirais/química , Antivirais/farmacologia , COVID-19 , Linhagem Celular , Colite Ulcerativa/tratamento farmacológico , Citocinas/genética , Citocinas/metabolismo , Dopamina/metabolismo , Frutas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos , Inflamação/tratamento farmacológico , Masculino , Camundongos , Extratos Vegetais/química , Prunus/química , Serina Endopeptidases/metabolismo
17.
Molecules ; 26(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34361588

RESUMO

Psophocarpus tetragonolobus has long been used in traditional medicine and cuisine. In this study, Psophocarpus tetragonolobus extracts were isolated by maceration and ultrasound-assisted extraction and were evaluated for their antioxidant and anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The obtained results show that both extracts (maceration and ultrasound) were rich in bioactive molecules and exerted substantial antioxidant and anti-inflammatory effects. The P. tetragonolobus extracts' treatment in LPS-stimulated RAW264.7 macrophages resulted in a significant downregulation of the expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß mRNA. In addition, the P. tetragonolobus extracts' treatment attenuated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression. Our observations indicate that there is no significant difference between the two studied extracts of P. tetragonolobus in terms of biological properties (specifically, antioxidant and anti-inflammatory effects. Regardless of the extraction method, P. tetragonolobus could be used for treating diseases related to oxidative stress and inflammatory reactions.


Assuntos
Anti-Inflamatórios , Antioxidantes , Fabaceae/química , Macrófagos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células RAW 264.7 , Ondas Ultrassônicas
18.
Molecules ; 26(15)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34361637

RESUMO

Ganoderma lucidum extract is a potent traditional remedy for curing various ailments. Drying is the most important postharvest step during the processing of Ganoderma lucidum. The drying process mainly involves heat (36 h at 60 °C) and freeze-drying (36 h at -80 °C). We investigated the effects of different postharvest drying protocols on the metabolites profiling of Ganoderma lucidum using GC-MS, followed by an investigation of the anti-neuroinflammatory potential in LPS-treated BV2 microglial cells. A total of 109 primary metabolites were detected from heat and freeze-dried samples. Primary metabolite profiling showed higher levels of amino acids (17.4%) and monosaccharides (8.8%) in the heat-dried extracts, whereas high levels of organic acids (64.1%) were present in the freeze-dried samples. The enzymatic activity, such as ATP-citrate synthase, pyruvate kinase, glyceraldehyde-3-phosphatase dehydrogenase, glutamine synthase, fructose-bisphosphate aldolase, and D-3-phosphoglycerate dehydrogenase, related to the reverse tricarboxylic acid cycle were significantly high in the heat-dried samples. We also observed a decreased phosphorylation level of the MAP kinase (Erk1/2, p38, and JNK) and NF-κB subunit p65 in the heat-dried samples of the BV2 microglia cells. The current study suggests that heat drying improves the production of ganoderic acids by the upregulation of TCA-related pathways, which, in turn, gives a significant reduction in the inflammatory response of LPS-induced BV2 cells. This may be attributed to the inhibition of NF-κB and MAP kinase signaling pathways in cells treated with heat-dried extracts.


Assuntos
Anti-Inflamatórios , Antineoplásicos Fitogênicos , Neoplasias/tratamento farmacológico , Reishi/química , Metabolismo Secundário , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Dessecação , Camundongos , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia
19.
Molecules ; 26(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34443474

RESUMO

Numerous plant compounds and their metal-ion complexes exert antioxidative, anti-inflammatory, anticancer, and other beneficial effects. This review highlights the different bioactivities of flavonoids, chromones, and coumarins and their metal-ions complexes due to different structural characteristics. In addition to insight into the most studied antioxidative properties of these compounds, the first part of the review provides a comprehensive overview of exogenous and endogenous sources of reactive oxygen and nitrogen species, oxidative stress-mediated damages of lipids and proteins, and on protective roles of antioxidant defense systems, including plant-derived antioxidants. Additionally, the review covers the anti-inflammatory and antimicrobial activities of flavonoids, chromones, coumarins and their metal-ion complexes which support its application in medicine, pharmacy, and cosmetology.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Complexos de Coordenação/química , Íons/química , Metais/química , Compostos Fitoquímicos/farmacologia , Anti-Inflamatórios/química , Antioxidantes/química , Radicais Livres/metabolismo , Humanos , Compostos Fitoquímicos/química , Plantas/química
20.
Molecules ; 26(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34443483

RESUMO

Skeletal muscle atrophy is the decrease in muscle mass and strength caused by reduced protein synthesis/accelerated protein degradation. Various conditions, such as denervation, disuse, aging, chronic diseases, heart disease, obstructive lung disease, diabetes, renal failure, AIDS, sepsis, cancer, and steroidal medications, can cause muscle atrophy. Mechanistically, inflammation, oxidative stress, and mitochondrial dysfunction are among the major contributors to muscle atrophy, by modulating signaling pathways that regulate muscle homeostasis. To prevent muscle catabolism and enhance muscle anabolism, several natural and synthetic compounds have been investigated. Recently, polyphenols (i.e., natural phytochemicals) have received extensive attention regarding their effect on muscle atrophy because of their potent antioxidant and anti-inflammatory properties. Numerous in vitro and in vivo studies have reported polyphenols as strongly effective bioactive molecules that attenuate muscle atrophy and enhance muscle health. This review describes polyphenols as promising bioactive molecules that impede muscle atrophy induced by various proatrophic factors. The effects of each class/subclass of polyphenolic compounds regarding protection against the muscle disorders induced by various pathological/physiological factors are summarized in tabular form and discussed. Although considerable variations in antiatrophic potencies and mechanisms were observed among structurally diverse polyphenolic compounds, they are vital factors to be considered in muscle atrophy prevention strategies.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Compostos Fitoquímicos/farmacologia , Polifenóis/farmacologia , Animais , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antioxidantes/efeitos adversos , Antioxidantes/química , Antioxidantes/uso terapêutico , Humanos , Compostos Fitoquímicos/efeitos adversos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico , Polifenóis/efeitos adversos , Polifenóis/química , Polifenóis/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
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