RESUMEN
The global COVID-19 pandemic remains a critical public health threat, as existing vaccines and drugs appear insufficient to halt the rapid transmission. During an outbreak from May to August 2021 in Taiwan, patients with severe COVID-19 were administered NRICM102, which was a traditional Chinese medicine (TCM) formula developed based on its predecessor NRICM101 approved for treating mild cases. This study aimed to explore the mechanism of NRICM102 in ameliorating severe COVID-19-related embolic and fibrotic pulmonary injury. NRICM102 was found to disrupt spike protein/ACE2 interaction, 3CL protease activity, reduce activation of neutrophils, monocytes and expression of cytokines (TNF-α, IL-1ß, IL-6, IL-8), chemokines (MCP-1, MIP-1, RANTES) and proinflammatory receptor (TLR4). NRICM102 also inhibited the spread of virus and progression to embolic and fibrotic pulmonary injury through reducing prothrombotic (vWF, PAI-1, NET) and fibrotic (c-Kit, SCF) factors, and reducing alveolar type I (AT1) and type II (AT2) cell apoptosis. NRICM102 may exhibit its protective capability via regulation of TLRs, JAK/STAT, PI3K/AKT, and NET signaling pathways. The study demonstrates the ability of NRICM102 to ameliorate severe COVID-19-related embolic and fibrotic pulmonary injury in vitro and in vivo and elucidates the underlying mechanisms.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Lesión Pulmonar , Embolia Pulmonar , Enzima Convertidora de Angiotensina 2 , Quimiocina CCL5 , Citocinas , Fibrosis , Humanos , Interleucina-6/metabolismo , Interleucina-8 , Lesión Pulmonar/tratamiento farmacológico , Pandemias , Fosfatidilinositol 3-Quinasas , Inhibidor 1 de Activador Plasminogénico , Proteínas Proto-Oncogénicas c-akt , Embolia Pulmonar/tratamiento farmacológico , Glicoproteína de la Espiga del Coronavirus , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de von WillebrandRESUMEN
The aim of this study was to develop a multi-analyte UHPLC method for furans and to apply it to commercial coffee samples as well as commercial roasting trials. Furans, as rising time-temperature indicators (TTIs), promised to be an alternative to unsatisfactory roasting temperature measurements. Consequently, a UHPLC-UV method for the determination of 5-hydroxymethyl-2-furfural (HMF), 5-hydroxymethyl-2-furoic acid (HMFA), 2-furfural (F), 5-methylfurfural (MF), 2-furyl methyl ketone (FMC), 2-furoic acid (FA), and for 3-caffeoylquinic acid (3-CQA) was developed and validated. Commercial roasted coffee beans contained 77.7-322 mg/kg HMF, 73.3-158 mg/kg HMFA, 109-200 mg/kg 2-F, 157-209 mg/kg MF, 12.3-32.8 mg/kg FMC, and 137-205 mg/kg FA. Roasting trial samples showed strong rising HMF contents (max.: Arabica: 769 mg/kg, Robusta: 364 mg/kg) followed by a distinct decline. Only MF and FA appeared as steady rising TTIs in the roasting process in Arabica and Robusta beans. 3-CQA fitted well as a decreasing TTI as expected.
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Cromatografía Líquida de Alta Presión/métodos , Café/química , Furanos/análisis , Semillas/química , Ácido Clorogénico/análisis , Análisis de los Alimentos/métodos , Industria de Procesamiento de Alimentos/métodos , Furaldehído/análogos & derivados , Furaldehído/análisis , CalorRESUMEN
The present study was aimed at the investigation, through HPLCDAD-ESI-MS/MS, of polyphenols in seven autochthonous C. intybus varieties, already known from literature to contain various substances with antioxidant properties, from the Veneto region of Italy, namely 'Castelfranco', 'Chioggia', 'Rosa di Gorizia', 'Rosa di Verona', 'Treviso Precoce', 'Treviso Tardivo' and 'Verdon da Cortèl'. Thirteen polyphenols, belonging to hydroxycinnamic acid, flavone, flavonol and anthocyanin classes, were detected in most samples. The developed analytical method was validated in agreement with ICH guidelines. The total amount of polyphenols ranged from 52 to 386 (mean: 254)â¯mg/100g fresh weight (F.W.). The results were further confirmed by Principal Composition Analysis (PCA), which highlighted peculiar features and similarities among analysed samples for each variety (except for 'Chioggia' samples). The developed method is suitable for routine analyses, as well as geographical characterization, selection of different C. intybus varieties and for the determination of related polyphenols dietary recommended intakes.
Asunto(s)
Cichorium intybus/química , Flavonoides/análisis , Polifenoles/análisis , Antioxidantes/análisis , Cromatografía Líquida de Alta Presión , Italia , Extractos Vegetales/análisis , Espectrometría de Masas en TándemRESUMEN
The Chilean wild currants Ribes magellanicum and R. punctatum are a good source of polyphenols. Polyphenolic-enriched extracts (PEEs) from both species were submitted to in vitro colonic fermentation to assess the changes in phenolic composition, antioxidant capacity and inhibition of metabolic syndrome-associated enzymes. The phenolic profiles of the fermented samples showed significant changes after 24â¯h incubation. Nine metabolites, derived from the microbial fermentation, were tentatively identified, including dihydrocaffeic acid, dihydrocaffeoyl-, dihydroferuloylquinic acid, 1-(3,4-dihydroxyphenyl)-3-(2,4,6-trihydroxyphenyl)propan-2-ol (3,4-diHPP-2-ol), among others. The content of anthocyanins and hydroxycinnamic acids was most affected by simulated colonic conditions, with a loss of 71-92% and 90-100% after 24â¯h incubation, respectively. The highest antioxidant capacity values (ORAC) were reached after 8â¯h incubation. The inhibitory activity against the enzyme α-glucosidase was maintained after the fermentation process. Our results show that simulated colonic fermentation exerts significant changes on the polyphenolic composition of these berries, modifying their health-promoting properties.
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Antioxidantes/química , Polifenoles/análisis , Ribes/química , Adulto , Antocianinas/análisis , Antocianinas/química , Bacterias/crecimiento & desarrollo , Bacterias/aislamiento & purificación , Reactores Biológicos , Chile , Cromatografía Líquida de Alta Presión , Ácidos Cumáricos/análisis , Ácidos Cumáricos/química , Heces/microbiología , Frutas/química , Frutas/metabolismo , Humanos , Masculino , Ribes/metabolismo , Espectrometría de Masa por Ionización de Electrospray , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismo , alfa-Glucosidasas/química , alfa-Glucosidasas/metabolismoRESUMEN
The wild Chilean currants Ribes magellanicum and R. punctatum are a good source of polyphenolic compounds. The effect of simulated gastrointestinal digestion (GID) on phenolic content, composition and antioxidant capacity was determined. The inhibitory activity of the non-digested and digested samples towards metabolic syndrome-associated enzymes (α-amylase, α-glucosidase and lipase) was evaluated. The total phenolic (TP) and flavonoid contents (TF) decreased by about 50% at the end of the in vitro GID. Main anthocyanins and hydroxycinnamic acids were strongly affected by this process, with a loss of about 80%. A decrease in the antioxidant activity was observed throughout the digestion steps, which was correlated with the reduction in the TP and TF content. After the in vitro GID of the samples, only the inhibition of α-glucosidase was preserved. Our results show that the simulated GID modified the health-promoting properties of the studied currants.
Asunto(s)
Ribes , Antocianinas , Antioxidantes , Tracto Gastrointestinal , Humanos , Extractos Vegetales , PolifenolesRESUMEN
In this work, impact of extraction methods (maceration, decoction, MAE, and UAE) on TPC, antioxidant activity, and the mass fraction of phenolics in several plant extracts (Punica granatum, Juglans regia, Moringa oleifera, and Cassia fistula) was investigated. The results showed that, despite the nature of matrix, the highest values of TPC in all samples were obtained by MAE as follows: PP (18.92±0.11), ML (15.19±0.11), HL (12.69±0.16), and WS (12.80±0.11) mg GAEg-1 respectively, and exhibited potent antioxidant activity (from 0.28±0.01 to 5.34±0.02mgGAEg-1), representing sources of powerful antioxidants. The LC-MS2 analysis revealed a wide range of phenolics, highlighting their content in phenolic acids, flavonoids and lignans. The presence of different phenol molecules demonstrated that the extraction method had influence on phytochemical profile. Finally, due to its high extraction efficiency, MAE was the more effective extraction technique.
Asunto(s)
Antioxidantes/metabolismo , Fitoquímicos/análisis , Extractos Vegetales/química , Polifenoles/química , Flavonoides , Fenoles , Extractos Vegetales/análisisRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Bu-Fei decoction (BFD) has been utilized to treat patients with Qi deficiency for decades, with the advantages of invigorating vital energy, clearing heat-toxin and moistening lung, etc. According to previous clinical experience and trials, BFD has been found to indeed improve life quality of lung cancer patients and prolong survival time. Nevertheless, little is known on its potential mechanisms so far. Being regarded as a pivotal cytokine in the tumor microenvironment, transforming growth factor ß (TGF-ß) stands out as a robust regulator of epithelial-mesenchymal transition (EMT), which is closely linked to tumor progression. AIM OF THE STUDY: The present study was designed to explore whether BFD antagonized EMT via blocking TGF-ß1-induced signaling pathway, and then help contribute to create a relatively steady microenvironment for confining lung cancer. MATERIALS AND METHODS: This experiment was performed in lung adenocarcinoma A549 cells both in vitro and in vivo. In detail, the influences mediated by TGF-ß1 alone or in combination with different concentrations of BFD on migration were detected by wound healing and transwell assays, and the effects of BFD on cell viability were determined by cell counting kit-8 (CCK-8) assay. TGF-ß1, EMT relevant proteins and genes were evaluated by western blotting, confocal microscopy, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) and enzyme-linked immuno sorbent assay (ELISA). Female BALB/C nude mice were subcutaneously implanted A549 cells and given BFD by gavage twice daily for 28 days. The tumor volume was monitored every 4 days to draw growth curve. The tumor weight, expression levels of EMT-related protein in tumor tissues and TGF-ß1 serum level were evaluated, respectively. RESULTS: BFD only exerted minor effects on A549 cell proliferation and this was in accordance with the in vivo result, which showed that the tumor growth and weight were not be restrained by BFD administration. However, the data elucidated that BFD could dose-dependently suppress EMT induced by TGF-ß1 in vitro via attenuating canonical Smad signaling pathway. In the A549 xenograft mouse model, BFD also inhibited protein markers that are associated with EMT and TGF-ß1 secretion into serum. CONCLUSIONS: Based on these above data, the conclusion could be put forward that BFD probably attenuated TGF-ß1 mediated EMT in A549 cells via decreasing canonical Smad signaling pathway both in vitro and in vivo, which may help restrain the malignant phenotype induced by TGF-ß1 in A549 cells to some extent.
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Antineoplásicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Células A549 , Animales , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones Endogámicos BALB C , Transducción de Señal/efectos de los fármacos , Proteínas Smad/genética , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/sangre , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
This study aimed to evaluate the antioxidant potential of Artemisia selengensis Turcz (AST) leaves, a byproduct when processing AST stalk, and identify the antioxidant constituents by using HPLC-QTOF-MS(2). The total phenolics content (TPC), total flavonoids content (TFC) and antioxidant abilities of fractions resulted from the successively partition of chloroform, ethyl acetate and n-butanol were compared. Ethyl acetate fraction (EAF) exhibited the highest TFC (65.44 mg QuE/g fraction), n-butanol fraction (nBuF) showed the highest TPC (384.78 mg GAE/g fraction) and the best DPPH scavenging ability, ABTS(+) scavenging ability and reducing power. Totally, 57 compounds were identified or tentatively identified in nBuF and EAF, 40 of them were reported in AST for the first time. The major constituents in EAF were flavonoids, and the major constituents in nBuF were phenolic acids and organic acids. Thus, AST leaves might be a potential low-cost resource of natural antioxidants.