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1.
J Ethnopharmacol ; 301: 115828, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36240979

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal properties of Gaultheria have been used in traditional medicine to treat pain and inflammation. AIM OF THE STUDY: Hence, the purpose of this study was to evaluate the analgesic, antipyretic, and anti-inflammatory properties of Gaultheria trichophylla Royle extract and salicylate-rich fraction in vivo, in vitro, and in silico. MATERIALS AND METHODS: In vivo analgesic, antipyretic, and anti-inflammatory of extract and a salicylate-rich fraction (at doses of 100, 200, 300, and 150 mg/kg) were assessed using healthy albino mice employing acetic acid-induced writhing, tail immersion test, carrageenan-induced inflammation, and croton oil-induced edema. For in vitro testing of extracts COX and LOX enzyme inhibition assays were used. Molecular docking studies were conducted for in silico testing of the inhibitory activity of the dominant compound Gaultherin against COX and LOX. RESULTS: G-EXT 200 and 300 and G-SAL 150 mg/kg reduced pyrexia significantly (P < 0.05 and P < 0.01). G-EXT-200, 300, and G-SAL 150 reduce the writing to a significant level (p > 0.05, p < 0.01). G-EXT 200 and 300 and G-SAL 150 mg/kg doses the analgesic effect was significant (p > 0.05, p > 0.01) and was comparable to tramadol. G-EXT 100 200, 300 mg/kg showed 43.8%, 47.94% and 56% respectively. G-SAL 150 mg, rich in salicylates, showed maximum inhibition of 65.75% next to standard drug diclofenac with 76.7% inhibition. G-EXT 100 and 200 mg/kg dose showed significant (p < 0.05) reduction in ear edema. With 300 mg/kg dose the effect was more (61.89%, p < 0.01). The salicylate-rich fraction G-SAL and Celecoxib showed an almost similar effect (p < 0.01). Significance inhibition was shown in the COX-2 test (G-EXT 39.70 and G-SAL 77.20 IC50 µg/ml) and in the 5-LOX test (G-EXT 28.3 and G-SAL 39.70 IC50 µg/ml). The preliminary in silico results suggest that the investigated compound showed excellent inhibitory activity against COX and LOX enzymes as evident from the free binding energy. Molecular docking revealed that Gaultherin binds well in the COX and LOX enzyme catalytic region. CONCLUSION: The extract and salicylate-rich fraction obtained from G. trichophylla showed significant analgesic, anti-inflammatory, and antipyretic effects in vivo, in vitro, and in silico assays that support its use in traditional medicine.


Assuntos
Antipiréticos , Ericaceae , Gaultheria , Animais , Camundongos , Gaultheria/química , Antipiréticos/farmacologia , Simulação de Acoplamento Molecular , Anti-Inflamatórios/efeitos adversos , Analgésicos/efeitos adversos , Salicilatos/química , Salicilatos/farmacologia , Salicilatos/uso terapêutico , Febre/tratamento farmacológico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Carragenina , Inflamação/tratamento farmacológico
2.
Sci Rep ; 12(1): 20527, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443410

RESUMO

Pollution of the environment by crude oil and oil products (represented by various types of compounds, mainly aliphatic, mono- and polyaromatic hydrocarbons) poses a global problem. The strain Pseudomonas veronii 7-41 can grow on medium-chain n-alkanes (C8-C12) and polycyclic aromatic hydrocarbons such as naphthalene. We performed a genetic analysis and physiological/biochemical characterization of strain 7-41 cultivated in a mineral medium with decane, naphthalene or a mixture of the hydrocarbons. The genes responsible for the degradation of alkanes and PAHs are on the IncP-7 conjugative plasmid and are organized into the alk and nah operons typical of pseudomonads. A natural plasmid carrying functional operons for the degradation of two different classes of hydrocarbons was first described. In monosubstrate systems, 28.4% and 68.8% of decane and naphthalene, respectively, were biodegraded by the late stationary growth phase. In a bisubstrate system, these parameters were 25.4% and 20.8% by the end of the exponential growth phase. Then the biodegradation stopped, and the bacterial culture started dying due to the accumulation of salicylate (naphthalene-degradation metabolite), which is toxic in high concentrations. The activity of the salicylate oxidation enzymes was below the detection limit. These results indicate that the presence of decane and a high concentration of salicylate lead to impairment of hydrocarbon degradation by the strain.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Alcanos , Naftalenos , Biodegradação Ambiental , Salicilatos
3.
Neurotoxicology ; 93: 301-310, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36330896

RESUMO

It is known that ototoxicity is the main cause of toxicity induced by aminoglycoside antibiotics. Effects on cochlea and vestibule in vertebrates are variable, depending on the typology of the aminoglycoside and the animal model examined. Despite this, they are routinely used to prevent postoperative and urinary tract infections and in the treatment of tuberculosis and cystic fibrosis. Gentamicin causes hearing loss by damaging stereocilia and by causing degeneration of hair cells due to free radical formation and eventual activation of caspase-dependent pathways. Its toxicity increases with the frequency of administration, dose concentration, and duration of treatment. Turnover of new hair cells may occur spontaneously, throughout life, or may be triggered by an acoustic or ototoxic insult to replace dead cells. Turnover and repair of damage are common in fish and amphibians and in birds' vestibule. In contrast, in the papilla basilaris of birds, and in the vestibule of mammals, hair cell regeneration is activated only after damage. Sensory epithelium repair and hair cell regeneration also occur in the reptiles' vestibule, but no data is available on regeneration or repair in the basilar papilla, involved in sound perception. The purpose of this work is therefore to assess the damage induced by gentamicin on the papilla basilaris of a reptile model organism, the Lacertidae Podarcis siculus. Recovery was also evaluated 3, 8 and 18 days after the end of exposure, in absence of gentamicin and in presence of the otoprotective salicylate. Scanning electron microscopy (SEM) was carried out to check for morphological damage while the occurrence of cell proliferation events was evaluated by fluorescence microscopy, after administration of 5-Bromo-2'-deoxyuridine (BrdU). Results show that salicylate administration facilitates recovery and reduces damage to hair cells after gentamicin treatment. Following the incorporation of bromodeoxyuridine, we demonstrated that sensory epithelium repair and hair cell regeneration have occurred, and that the recovery is due to either proliferation of the supporting cells and/or self-repair of hair cell bundles in the weakly damaged sensory cells.


Assuntos
Lagartos , Ototoxicidade , Animais , Gentamicinas/toxicidade , Ototoxicidade/prevenção & controle , Salicilatos , Órgão Espiral , Antibacterianos/toxicidade , Bromodesoxiuridina , Mamíferos
4.
Molecules ; 27(22)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36431878

RESUMO

Ginkgols are active constituents from Ginkgo biloba L. (GB) and have pharmacological activities, such as antibacterial and antioxidant activities. In our previous report, only five ginkgols were separated. However, ginkgol C17:1 had two isomers, for which their separation, identification, and bioactivities have not yet been investigated. Hence, this research reports the successful isolation of six ginkgol homologs with alkyl substituents-C17:1-Δ12, C15:1-Δ8, C13:0, C17:2, C17:1-Δ10, and C15:0-for the first time using HPLC. This was followed by the identification of their chemical structures using Fourier transform infrared (FTIR), ultraviolet (UV), gas chromatography and mass spectrometry (GC-MS), carbon-13 nuclear magnetic resonance (13C-NMR), and proton nuclear magnetic resonance (1H-NMR) analysis. The results showed that two ginkgol isomers, C17:1-Δ12 and C17:1-Δ10, were obtained simultaneously from the ginkgol C17:1 mixture and identified entirely for the first time. That aside, the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay showed that the six ginkgol homologs possessed significant antiproliferation effects against HGC and HepG2 cells. Furthermore, the ginkgols with unsaturated side chains (C17:2, C15:1-Δ8, C17:1-Δ12, and C17:1-Δ10) exhibited more potent inhibitory effects than ginkgols with saturated side chains (C13:0, C15:0). In addition, unsaturated ginkgol C15:1-Δ8 showed the most potent cytotoxicity on HepG2 and HGC cells, of which the half-maximal inhibition concentrations (IC50) were 18.84 ± 2.58 and 13.15 ± 2.91 µM, respectively. The IC50 for HepG2 and HGC cells for the three unsaturated ginkgols (C17:1-Δ10, C17:2 and C17:1-Δ12) were ~59.97, ~60.82, and ~68.97 µM for HepG2 and ~30.97, ~33.81, and ~34.55 µM for HGC cells, respectively. Comparing the ginkgols' structure-activity relations, the findings revealed that the position and number of the double bonds of the ginkgols with 17 side chain carbons in length had no significant difference in anticancer activity.


Assuntos
Ginkgo biloba , Salicilatos , Ginkgo biloba/química , Salicilatos/química , Cromatografia Gasosa-Espectrometria de Massas , Cromatografia Líquida de Alta Pressão , Fenômenos Químicos
5.
Int J Mol Sci ; 23(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36430660

RESUMO

To date, the effect of resveratrol on tinnitus has not been reported. The attenuative effects of resveratrol (RSV) on a salicylate-induced tinnitus model were evaluated by in vitro and in vivo experiments. The gene expression of the activity-regulated cytoskeleton-associated protein (ARC), tumor necrosis factor-alpha (TNFα), and NMDA receptor subunit 2B (NR2B) in SH-SY5Y cells was examined using qPCR. Phosphorylated cAMP response element-binding protein (p-CREB), apoptosis markers, and reactive oxygen species (ROS) were evaluated by in vitro experiments. The in vivo experiment evaluated the gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and auditory brainstem response (ABR) level. The NR2B expression in the auditory cortex (AC) was determined by immunohistochemistry. RSV significantly reduced the salicylate-induced expression of NR2B, ARC, and TNFα in neuronal cells; the GPIAS and ABR thresholds altered by salicylate in rats were recovered close to their normal range. RSV also reduced the salicylate-induced NR2B overexpression of the AC. These results confirmed that resveratrol exerted an attenuative effect on salicylate-induced tinnitus and may have a therapeutic potential.


Assuntos
Neuroblastoma , Resveratrol , Zumbido , Animais , Humanos , Ratos , Ratos Sprague-Dawley , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Salicilatos/farmacologia , Zumbido/induzido quimicamente , Zumbido/tratamento farmacológico , Zumbido/patologia , Fator de Necrose Tumoral alfa/uso terapêutico , Modelos Animais de Doenças
6.
Commun Biol ; 5(1): 1239, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371560

RESUMO

Engineering microbes to produce plant-derived natural products provides an alternate solution to obtain bioactive products. Here we report a systematic approach to sequentially identify the rate-limiting steps and improve the biosynthesis of the cannabinoid precursor olivetolic acid (OLA) in Yarrowia lipolytica. We find that Pseudomonas sp LvaE encoding a short-chain acyl-CoA synthetase can efficiently convert hexanoic acid to hexanoyl-CoA. The co-expression of the acetyl-CoA carboxylase, the pyruvate dehydrogenase bypass, the NADPH-generating malic enzyme, as well as the activation of peroxisomal ß-oxidation pathway and ATP export pathway are effective strategies to redirect carbon flux toward OLA synthesis. Implementation of these strategies led to an 83-fold increase in OLA titer, reaching 9.18 mg/L of OLA in shake flask culture. This work may serve as a baseline for engineering cannabinoids biosynthesis in oleaginous yeast species.


Assuntos
Canabinoides , Yarrowia , Yarrowia/genética , Canabinoides/metabolismo , Engenharia Metabólica , Salicilatos/metabolismo
7.
Org Biomol Chem ; 20(41): 8078-8082, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36200479

RESUMO

An electrochemical carbenoid insertion reaction of diazo compounds into C-S and C-O bonds with electricity as the oxidant has been reported in this work. In this protocol, this transformation proceeded smoothly under mild conditions at room temperature in the absence of a catalyst and a ligand. In addition, the yield of the S-H insertion product was up to 96% and the O-H product could be efficiently obtained in up to 80% yield. Of note is that this environmentally friendly strategy exhibited excellent applicability in gram-scale synthesis.


Assuntos
Ésteres , Compostos de Sulfidrila , Ésteres/química , Salicilatos , Ligantes , Oxidantes
8.
Genes (Basel) ; 13(10)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36292584

RESUMO

Melatonin was discovered in plants in the late nineties, but its role, signaling, and crosstalk with other phytohormones remain unknown. Research on melatonin in plants has risen dramatically in recent years and the role of this putative plant hormone under biotic and abiotic stress conditions has been reported. In the present review, we discuss the main functions of melatonin in the growth and development of plants, its role under abiotic stresses, such as water stress (waterlogging and drought), extreme temperature (low and high), salinity, heavy metal, and light-induced stress. Similarly, we also discuss the role of melatonin under biotic stresses (antiviral, antibacterial, and antifungal effects). Moreover, the present review meticulously discusses the crosstalk of melatonin with other phytohormones such as auxins, gibberellic acids, cytokinins, ethylene, and salicylic acid under normal and stressful conditions and reports melatonin receptors and signaling in plants. All these aspects of melatonin suggest that phytomelatonin is a key player in crop improvement and biotic and abiotic stress regulation.


Assuntos
Melatonina , Reguladores de Crescimento de Plantas , Reguladores de Crescimento de Plantas/farmacologia , Receptores de Melatonina , Antifúngicos/farmacologia , Plantas , Citocininas , Etilenos/farmacologia , Ácidos Indolacéticos , Antibacterianos/farmacologia , Antivirais/farmacologia , Salicilatos/farmacologia
9.
J Org Chem ; 87(21): 14005-14015, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36210518

RESUMO

A facile and effective tandem reaction of ynones and methyl salicylates was developed to obtain a broad range of 3-acyl chromones in moderate-to-excellent yields. This protocol underwent a Michael addition and cyclization process, which exhibited easily accessible substrates, broad substrate scope, and high regioselectivity under mild and transition-metal-free conditions. Moreover, gram-scale reaction and further chemical transformation of the products were also further studied.


Assuntos
Cromonas , Elementos de Transição , Estereoisomerismo , Ciclização , Salicilatos
10.
Sci Rep ; 12(1): 16842, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207349

RESUMO

High expression of polymeric immunoglobulin receptor (PIGR) in breast cancer is associated with increased 5-year survival rate. However, the factors influencing PIGR expression in breast cancer have not been elucidated. The aim of this study was to determine the role of macrophages and cytokines affecting expression of PIGR in two breast cancer cell lines. M1, M2 macrophage conditioned media (CM) and recombinant human cytokines were used to determine factors which increased PIGR expression in MCF7 (HTB-22) and MDA-MB468 (HTB-132) breast cancer cell lines. The level of PIGR expression in the cells and PIGR secretory component were evaluated by real-time quantitative polymerase chain reaction and Western blotting. M1 macrophage CM induced a dose-dependent increase in PIGR mRNA expression in MDA-MB468 cells, up to 20-fold. The level of PIGR expression in MCF7 cells was very low and not affected by M1 and M2 CM. Interferon gamma (IFN-γ) and interleukin (IL)-1ß also increased PIGR expression in MDA-MB468 and MCF7 cells. However, IL-1ß was demonstrated to increase in M1 macrophages, while IFN-γ was not. The role of IL-1ß secreted from M1 macrophages in increasing expression of PIGR was confirmed by IL-1 receptor blockade, indicating that IL-1ß was the major M1 macrophage-derived cytokine that enhanced PIGR expression. Elevated PIGR expression in breast cancer in vivo may reflect the polarization state of tumor-associated immune cells.


Assuntos
Neoplasias da Mama , Receptores de Imunoglobulina Polimérica , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Meios de Cultivo Condicionados/farmacologia , Citocinas/metabolismo , Feminino , Humanos , Interferon gama/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , RNA Mensageiro/metabolismo , Receptores de Interleucina-1/metabolismo , Receptores de Imunoglobulina Polimérica/genética , Receptores de Imunoglobulina Polimérica/metabolismo , Salicilatos , Componente Secretório
11.
Cells ; 11(19)2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36230898

RESUMO

The cytoprotective effects of a novel hydroalcoholic extract (0.01-5 mg/mL) from Lens culinaria (Terre di Altamura Srl) were investigated within murine native skeletal muscle fibers, bone marrow cells, and osteoblasts, and in cell lines treated with the apoptotic agent staurosporine (2.14 × 10-6 M), the alkylating drug cisplatin (10-4 M), the topoisomerase I inhibitor irinotecan (10-4 M), the antimitotic pro-oxidant doxorubicin (10-6 M), and the immunosuppressant dexamethasone (2 × 10-6 M). An amount of 10g of plant material was used to obtain a 70% ethanol/water product, following two-step extraction, evaporation, lyophilization, and storage at -20 °C. For the murine osteoblasts, doxorubicin reduced survival by -65%, dexamethasone by -32% and -60% after 24 and 48 h of incubation time, respectively. The extract was effective in preventing the osteoblast count-reduction induced by dexamethasone; it was also effective at preventing the inhibition of mineralization induced by dexamethasone. Doxorubicin and cisplatin caused a significant reduction in cell growth by -77% for bone marrow cells, -43% for irinotecan, and -60% for dexamethasone, but there was no evidence for the cytoprotective effects of the extract in these cells. Staurosporine and doxorubicin caused a fiber death rate of >-40% after 18 and 24 h of incubation, yet the extract was not effective at preventing these effects. The extract was effective in preventing the staurosporine-induced reduction of HEK293 proliferation and colony formation in the crystal violet DNA staining and the clonogenic assays. It was also effective for the cisplatin-induced reduction in HEK293 cell proliferation. The extract, however, failed to protect the SHSY5Y neurons against cisplatin and irinotecan-induced cytotoxicity. A UV/VIS spectroscopy analysis showed three peaks at the wavelengths of 350, 260, and 190 nm, which correspond to flavonoids, proanthocyanins, salicylates, and AA, constituting the extract. These data suggest the possible development of this extract for use against dexamethasone-induced bone loss and renal chemotherapy-induced damage.


Assuntos
Antimitóticos , Dexametasona , Animais , Antimitóticos/metabolismo , Antimitóticos/farmacologia , Cisplatino/metabolismo , Cisplatino/farmacologia , Dexametasona/farmacologia , Doxorrubicina/farmacologia , Etanol/farmacologia , Flavonoides/farmacologia , Violeta Genciana/metabolismo , Violeta Genciana/farmacologia , Células HEK293 , Humanos , Imunossupressores/farmacologia , Irinotecano/farmacologia , Camundongos , Osteoblastos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Salicilatos/metabolismo , Salicilatos/farmacologia , Estaurosporina/farmacologia , Inibidores da Topoisomerase I/metabolismo , Inibidores da Topoisomerase I/farmacologia , Água/metabolismo
12.
ACS Chem Biol ; 17(11): 3169-3177, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36255735

RESUMO

Thermorubin is a tetracyclic naphthoisocoumarin natural product that demands investigation due to its novel mechanism of bacterial protein synthesis inhibition and its unusual structural features. In this work, we describe the identification of the biosynthetic cluster responsible for thermorubin from the sequenced Laceyella sacchari producer species and its confirmation via heterologous production in Escherichia coli. Based on an in-depth annotation of the cluster, we propose a biosynthetic pathway that accounts for the formation of the unique, nonterminal pyrone. Additionally, the expression and use of salicylate synthase TheO enabled testing of the stability properties of this extremophile-derived enzyme. TheO displayed rapid kinetics and a remarkably robust secondary structure, converting chorismate to salicylate with a KM of 109 ± 12 µM, kcat of 9.17 ± 0.36 min-1, and catalytic efficiency (kcat/KM) of 84 ± 9 nM-1 min-1, and retained significant activity up to 50 °C. These studies serve as the basis for continued biosynthetic investigations and bioinspired synthetic approaches.


Assuntos
Pironas , Salicilatos , Pironas/metabolismo , Salicilatos/metabolismo , Fenóis/metabolismo , Escherichia coli/metabolismo
13.
Nat Commun ; 13(1): 6208, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36266333

RESUMO

Outer hair cell elecromotility, driven by prestin, is essential for mammalian cochlear amplification. Here, we report the cryo-EM structures of thermostabilized prestin (PresTS), complexed with chloride, sulfate, or salicylate at 3.52-3.63 Å resolutions. The central positively-charged cavity allows flexible binding of various anion species, which likely accounts for the known distinct modulations of nonlinear capacitance (NLC) by different anions. Comparisons of these PresTS structures with recent prestin structures suggest rigid-body movement between the core and gate domains, and provide mechanistic insights into prestin inhibition by salicylate. Mutations at the dimeric interface severely diminished NLC, suggesting that stabilization of the gate domain facilitates core domain movement, thereby contributing to the expression of NLC. These findings advance our understanding of the molecular mechanism underlying mammalian cochlear amplification.


Assuntos
Proteínas de Transporte de Ânions , Cloretos , Animais , Proteínas de Transporte de Ânions/metabolismo , Cloretos/metabolismo , Microscopia Crioeletrônica , Células Ciliadas Auditivas Externas/metabolismo , Ânions/metabolismo , Salicilatos , Sulfatos/metabolismo , Mamíferos/metabolismo
14.
Int J Mol Sci ; 23(18)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36142555

RESUMO

Salicylic acid (SA) is a stress hormone synthesized in phenylalanine ammonia-lyase (PAL) and the branching acid pathway. SA has two interconvertible forms in plants: SAG (SA O-ß-glucoside) and SA (free form). The molecular mechanism of conversion of SA to SAG had been reported previously. However, which genes regulate SAG to SA remained unknown. Here, we report a cytoplasmic ß-glucosidase (ß-Glu) which participates in the SA pathway and is involved in the brown hull pigmentation in rice grain. In the current study, an EMS-generated mutant brown hull 1 (bh1) displayed decreased contents of SA in hulls, a lower photosynthesis rate, and high-temperature sensitivity compared to the wild type (WT). A plaque-like phenotype (brown pigmentation) was present on the hulls of bh1, which causes a significant decrease in the seed setting rate. Genetic analysis revealed a mutation in LOC_Os01g67220, which encodes a cytoplasmic Os1ßGlu4. The knock-out lines displayed the phenotype of brown pigmentation on hulls and decreased seed setting rate comparable with bh1. Overexpression and complementation lines of Os1ßGlu4 restored the phenotype of hulls and normal seed setting rate comparable with WT. Subcellular localization revealed that the protein of Os1ßGlu4 was localized in the cytoplasm. In contrast to WT, bh1 could not hydrolyze SAG into SA in vivo. Together, our results revealed the novel role of Os1ßGlu4 in the accumulation of flavonoids in hulls by regulating the level of free SA in the cellular pool.


Assuntos
Celulases , Oryza , Celulases/metabolismo , Flavonoides , Regulação da Expressão Gênica de Plantas , Glucosidases/metabolismo , Glucosídeos , Hormônios , Oryza/genética , Oryza/metabolismo , Fenilalanina Amônia-Liase/metabolismo , Pigmentação/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Salicilatos , Ácido Salicílico/metabolismo
15.
Molecules ; 27(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36144714

RESUMO

In this review, we discuss Friedel-Crafts-type aromatic amidation and acylation reactions, not exhaustively, but mainly based on our research results. The electrophilic species involved are isocyanate cation and acylium cation, respectively, and both have a common +C=O structure, which can be generated from carboxylic acid functionalities in a strong Brønsted acid. Carbamates substituted with methyl salicylate can be easily ionized to the isocyanate cation upon (di)protonation of the salicylate. Carboxylic acids can be used directly as a source of acylium cations. However, aminocarboxylic acids are inert in acidic media because two positively charged sites, ammonium and acylium cation, will be generated, resulting in energetically unfavorable charge-charge repulsion. Nevertheless, the aromatic acylation of aminocarboxylic acids can be achieved by using tailored phosphoric acid esters as Lewis bases to abrogate the charge-charge repulsion. Both examples tame the superelectrophilic character.


Assuntos
Compostos de Amônio , Bases de Lewis , Ácidos , Acilação , Carbamatos , Ácidos Carboxílicos , Cátions/química , Isocianatos/química , Estrutura Molecular , Organofosfatos , Salicilatos
16.
J Adv Res ; 40: 263-276, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36100331

RESUMO

INTRODUCTION: Ulcerative colitis (UC) is a chronic recurrent idiopathic disease characterized by damage to the colonic epithelial barrier and disruption of inflammatory homeostasis. At present, there is no curative therapy for UC, and the development of effective and low-cost therapies is strongly advocated. OBJECTIVES: Multiple lines of evidence support that tannic acid (TA) and berberine (BBR), two active ingredients derived from Chinese herb pair (Rhei Radix et Rhizoma and Coptidis Rhizoma), have promising therapeutic effects on colonic inflammation. This study aims to develop a targeted delivery system based on BBR/TA-based self-assemblies for the treatment of UC. METHODS: TA and BBR self-assemblies were optimized, and hyaluronic acid (HA) was coated to achieve targeted colon delivery via HA-cluster of differentiation 44 (CD44) interactions. The system was systematically characterized and dextran sodium sulfate (DSS)-induced mouse colitis model was further used to investigate the biodistribution behavior, effect and mechanism of the natural system. RESULTS: TA and BBR could self-assemble into stable particles (TB) and HA-coated TB (HTB) further increased cellular uptake and accumulation in inflamed colon lesions. Treatment of HTB inhibited pro-inflammatory cytokine levels, restored expression of tight junction-associated proteins and recovered gut microbiome alteration, thereby exerting anti-inflammatory effects against DSS-induced acute colitis. CONCLUSION: Our targeted strategy may provide a convenient and powerful platform for UC and reveal new modes of application of herbal combinations.


Assuntos
Antineoplásicos , Berberina , Colite Ulcerativa , Colite , Animais , Antineoplásicos/uso terapêutico , Benzopiranos , China , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos , Salicilatos , Taninos/metabolismo , Proteínas de Junções Íntimas/metabolismo , Distribuição Tecidual
17.
Food Funct ; 13(18): 9226-9242, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36065842

RESUMO

Ginkgo biloba leaf extract (EGb) is high in bioactive components (over 170), which are used in food additives, medicine, cosmetics, health products, and other sectors. Nonetheless, ginkgolic acids (GAs) in Ginkgo biloba (GB) have been identified as the primary source of EGb's adverse effects such as embryotoxicity, cytotoxicity, neurotoxicity, and inhibition of enzyme systems. As a result, the Chinese, European, and United States pharmacopeias all mandate that the GA concentration in EGb be less than 5 µg g-1. This review looked at the toxicity of ginkgolic acid (from in vitro and in vitro trials) as well as the technologies (such as adsorption/desorption, enzymatic degradation, counter-current chromatography, liquid-liquid microextraction, dual-frequency ultrasonic-solvent extraction, deep eutectic solvent, etc.) used to lower the GA to the desired concentration. These technologies' advantages, disadvantages, viability, and future trends were compared. In addition, several pharmacological significances of GA extraction, such as anti-microbial, anti-inflammatory, anti-tumor, etc., were discussed, as well as future directions.


Assuntos
Solventes Eutéticos Profundos , Ginkgo biloba , Aditivos Alimentares/análise , Ginkgo biloba/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Salicilatos/toxicidade
18.
J Plant Physiol ; 277: 153809, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36099699

RESUMO

Methyl salicylate is a volatile compound, the synthesis of which takes place via the salicylic acid pathway in plants. Both compounds can be involved in the development of systemic acquired resistance and they play their role partly independently. Salicylic acid transport has an important role in long-distance signalling, but methyl salicylate has also been suggested as a phloem-based mobile signal, which can be demethylated to form salicylic acid, inducing the de-novo synthesis of salicylic acid in distal tissue. Despite the fact that salicylic acid has a protective role in abiotic stress responses and tolerance, very few investigations have been reported on the similar effects of methyl salicylate. In addition, as salicylic acid and methyl salicylate are often treated simply as the volatile and non-volatile forms of the same compound, and in several cases they also act in the same way, it is hard to highlight the differences in their mode of action. The main aim of the present review is to reveal the individual role and action mechanism of methyl salicylate in systemic acquired resistance, plant-plant communication and various stress conditions in fruits and plants.


Assuntos
Desenvolvimento Vegetal , Ácido Salicílico , Floema/metabolismo , Plantas , Salicilatos , Ácido Salicílico/metabolismo
19.
J Agric Food Chem ; 70(39): 12587-12595, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36129228

RESUMO

Red wines produced without the addition of any SO2 are currently the source of a new consumer trend. The first characterization approaches regarding these specific wines were devoted to sensory studies that highlighted differences according to the use of SO2 during winemaking. The goal of this paper is to extend our knowledge of such aromatic specificities. Examining experimental wines produced with and without the addition of SO2, aroma fractionation, gas chromatography coupled with olfactometry, and mass spectrometry were applied to identify compounds at the origin of the specificities of these wines. Thus, we identified methyl salicylate as being impacted by the use of SO2 during the winemaking process. Studying a large number of commercial Bordeaux red wines, methyl salicylate was significantly quantified at a higher content in wines without added SO2. A sensory approach revealed a significant impact of methyl salicylate on wines without the sulfite aroma, particularly concerning fruity aromas and wine freshness.


Assuntos
Compostos Orgânicos Voláteis , Vinho , Cromatografia Gasosa-Espectrometria de Massas/métodos , Odorantes/análise , Salicilatos , Sulfitos/análise , Compostos Orgânicos Voláteis/química , Vinho/análise
20.
Clin Toxicol (Phila) ; 60(10): 1159-1162, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36069749

RESUMO

INTRODUCTION: Warfarin is a widely used oral anticoagulant with established reversal guidelines in the setting of a supratherapeutic international normalized ratio (INR). Limited literature exists on managing acute warfarin overdoses in patients who are not chronically anticoagulated. CASE: A 15-year-old male, with no indication for anticoagulation, presented to a pediatric emergency department after an acute 1,000 mg warfarin ingestion. He had no significant complaints upon presentation aside from a mild intermittent headache. His past medical history was significant for anxiety, depression, Tourette syndrome, attention deficit hyperactivity disorder, and polysubstance misuse. Computed tomography of his head was unremarkable and serum acetaminophen, salicylate, and ethanol concentrations were negative. Approximately 16 h post-ingestion, his INR was 1.9 with an increase to 3.3 by 26 h. The regional poison center was consulted and recommended, consistent with the CHEST guidelines, holding treatment with vitamin K until INR was >10 or if signs or symptoms of bleeding occurred. The patient was admitted for monitoring and by hospital day (HD) #4, his INR had risen to >11.8 at which point oral vitamin K 10 mg was administered. On HD #7, the patient was deemed stable for transfer to inpatient psychiatry after repeat INRs of 2.9 and 3.4. DISCUSSION: Case reports have demonstrated early administration of vitamin K can temporarily lower INR and prevent detection of rebound. The CHEST warfarin reversal guidelines describe the risks and benefits with respect to bleeding and thrombosis in the non-intentional overdose patient. Application and extrapolation of these guidelines to acute overdose in patients who lack an indication for anticoagulation may or may not be warranted. CONCLUSION: While established clinical guidance exists on reversing a supratherapeutic INR in patients chronically anticoagulated with warfarin, the risks and benefits of extrapolating this approach are unclear in those who lack an indication for anticoagulation.


Assuntos
Venenos , Varfarina , Masculino , Criança , Humanos , Adolescente , Varfarina/toxicidade , Varfarina/uso terapêutico , Acetaminofen/toxicidade , Anticoagulantes/uso terapêutico , Anticoagulantes/toxicidade , Coeficiente Internacional Normatizado , Vitamina K/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Salicilatos , Etanol
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