RESUMEN
ATP citrate lyase (ACLY) is a key enzyme in glucolipid metabolism, and abnormally high expression of ACLY occurs in many diseases, including cancers, dyslipidemia and cardiovascular diseases. ACLY inhibitors are prospective treatments for these diseases. However, the scaffolds of ACLY inhibitors are insufficient with weak activity. The discovery of inhibitors with structural novelty and high activity continues to be a research hotpot. Acanthopanax senticosus (Rupr. & Maxim.) Harms is used for cardiovascular disease treatment, from which no ACLY inhibitors have ever been found. In this work, we discovered three novel ACLY inhibitors, and the most potent one was isochlorogenic acid C (ICC) with an IC50 value of 0.14 ± 0.04 µM. We found dicaffeoylquinic acids with ortho-dihydroxyphenyl groups were important features for inhibition by studying ten phenolic acids. We further investigated interactions between the highly active compound ICC and ACLY. Thermal shift assay revealed that ICC could directly bind to ACLY and improve its stability in the heating process. Enzymatic kinetic studies indicated ICC was a noncompetitive inhibitor of ACLY. Our work discovered novel ACLY inhibitors, provided valuable structure-activity patterns and deepened knowledge on the interactions between this targe tand its inhibitors.
Asunto(s)
ATP Citrato (pro-S)-Liasa , Eleutherococcus , Eleutherococcus/química , Estructura Molecular , ATP Citrato (pro-S)-Liasa/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/química , Ácido Clorogénico/farmacología , Ácido Clorogénico/aislamiento & purificación , Ácido Clorogénico/química , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Fitoquímicos/química , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacología , Ácido Quínico/aislamiento & purificación , Ácido Quínico/química , Hidroxibenzoatos/farmacología , Hidroxibenzoatos/aislamiento & purificación , Hidroxibenzoatos/química , Relación Estructura-ActividadRESUMEN
Diabetes mellitus is a chronic disease affecting the globe and its incidence is increasing pandemically. The use of plant-derived natural products for diabetes management is of great interest. Polar fraction of Artemisia annua L. leaves has shown antidiabetic activity in vivo. In the present study, three major compounds were isolated from this polar fraction; namely, 3,5-dicaffeoylquinic acid (1); 4,5-dicaffeoylquinic acid (2), and 3,4- dicaffeoylquinic acid methyl ester (3), using VLC-RP-18 and HPLC techniques. The potential protective effects of these compounds against diabetes and its complications were investigated by employing various in vitro enzyme inhibition assays. Furthermore, their antioxidant and wound healing effectiveness were evaluated. Results declared that these dicaffeoylquinic acids greatly inhibited DPPIV enzyme while moderately inhibited α-glucosidase enzyme, where compounds 1 and 3 displayed the most prominent effects. In addition, compound 3 showed pronounced inhibition of α-amylase enzyme. Moreover, these compounds markedly inhibited aldose reductase enzyme and exerted powerful antioxidant effects, among which compound 3 exhibited the highest activity implying a notable potentiality in impeding diabetes complications. Interestingly, compounds 2 and 3 moderately accelerated scratch wound healing. Our findings suggest that these dicaffeoylquinic acids can be promising therapeutic agents for managing diabetes and its complications.
Asunto(s)
Artemisia annua/química , Complicaciones de la Diabetes/prevención & control , Inhibidores de Glicósido Hidrolasas , Hipoglucemiantes , Hojas de la Planta/química , Ácido Quínico/análogos & derivados , Línea Celular , Complicaciones de la Diabetes/metabolismo , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/farmacología , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Ácido Quínico/química , Ácido Quínico/aislamiento & purificación , Ácido Quínico/farmacologíaRESUMEN
CONTEXT: Chinese herbs such as Cortex Mori [Morus alba L. (Moraceae)] may inhibit human immunodeficiency virus (HIV), but active compounds are unknown. OBJECTIVE: Screening of Cortex Mori and other herbs for anti-HIV active compounds. MATERIALS AND METHODS: HIV-1 virus (multiplicity of infection: 20), and herbs (dissolved in dimethyl sulfoxide, working concentrations: 10, 1, and 0.1 mg/mL) such as Cortex Mori, etc., were added to 786-O cells (105 cell/well). Zidovudine was used as a positive control. Cell survival and viral inhibition rates were measured. The herb that was the closest inactivity to zidovudine was screened. Mass spectrometry identified the active compounds in herbs (mobile phase: 0.05% formic acid aqueous solution and acetonitrile, gradient elution, detection wavelength: 210 nm). The effect of the compounds on reverse transcriptase (RT) products were evaluated by real-time PCR. Gene enrichment was used to analyse underlying mechanisms. RESULTS: With a dose of 1 mg/mL of Cortex Mori, the cell survival rate (57.94%) and viral inhibition rate (74.95%) were closest to the effect of zidovudine (87.87%, 79.81%, respectively). Neochlorogenic acid, one of the active ingredients, was identified by mass spectrometry in Cortex Mori. PCR discovery total RT products of neochlorogenic acid group (mean relative gene expression: 6.01) significantly inhibited (control: 35.42, p < 0.0001). Enrichment analysis showed that neochlorogenic acid may act on haemopoietic cell kinase, epidermal growth factor receptor, sarcoma, etc., thus inhibiting HIV-1 infection. CONCLUSIONS: For people of low socioeconomic status affected by HIV, Chinese medicine (such as Cortex Mori) has many advantages: it is inexpensive and does not easily produce resistance. Drugs based on active ingredients may be developed and could have important value.
Asunto(s)
Fármacos Anti-VIH/farmacología , Ácido Clorogénico/análogos & derivados , Morus/química , Extractos Vegetales/farmacología , Ácido Quínico/análogos & derivados , Fármacos Anti-VIH/química , Fármacos Anti-VIH/aislamiento & purificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ácido Clorogénico/aislamiento & purificación , Ácido Clorogénico/farmacología , Relación Dosis-Respuesta a Droga , Células HEK293 , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Humanos , Extractos Vegetales/química , Ácido Quínico/aislamiento & purificación , Ácido Quínico/farmacología , Zidovudina/farmacologíaRESUMEN
The aim of the study was to investigate changes in the content of biologically active compounds during the fermentation and aging of natural meads with the addition of three Cornelian cherry juices from three cultivars: 'Koralovyi', 'Podolski' and 'Yantarnyi', in the amount of 10% v/v. After the fermentation process the content of gallic and ellagic acids significantly increased, in relation to wort. Whereas the greatest losses were observed among unstable anthocyanins. The three-month aging process also reduced the content of the analyzed compounds except for ellagic acid, the content of which increased by up to 90%. The content of biologically active compounds, including iridoids and antioxidant phenolics, are constantly changing in the process of fermentation and aging of fruit meads. The studies proved that the addition of Cornelian cherry juice allows significantly enriched classic meads with new biologically active compounds, such as: exceptional iridoids (loganic acid, cornuside, loganine, sweroside), flavonols, phenolic acids and anthocyanins.
Asunto(s)
Bebidas Alcohólicas/análisis , Tecnología de Alimentos/métodos , Miel/análisis , Iridoides/química , Fenoles/química , Saccharomyces/metabolismo , Antocianinas/biosíntesis , Antocianinas/química , Antocianinas/clasificación , Antocianinas/aislamiento & purificación , Antioxidantes/química , Antioxidantes/clasificación , Antioxidantes/aislamiento & purificación , Antioxidantes/metabolismo , Benzotiazoles/antagonistas & inhibidores , Compuestos de Bifenilo/antagonistas & inhibidores , Ácido Elágico/química , Ácido Elágico/aislamiento & purificación , Ácido Elágico/metabolismo , Fermentación , Flavonoles/química , Flavonoles/clasificación , Flavonoles/aislamiento & purificación , Flavonoles/metabolismo , Frutas/química , Jugos de Frutas y Vegetales/análisis , Ácido Gálico/química , Ácido Gálico/aislamiento & purificación , Ácido Gálico/metabolismo , Humanos , Iridoides/clasificación , Iridoides/aislamiento & purificación , Iridoides/metabolismo , Fenoles/clasificación , Fenoles/aislamiento & purificación , Fenoles/metabolismo , Picratos/antagonistas & inhibidores , Prunus avium/química , Ácido Quínico/análogos & derivados , Ácido Quínico/química , Ácido Quínico/aislamiento & purificación , Ácido Quínico/metabolismo , Ácidos Sulfónicos/antagonistas & inhibidoresRESUMEN
Owing to their antioxidant properties, caffeoylquinic acid (CQA)-derivatives could potentially improve the impaired metabolism in hepatic cells, however, their effect on mitochondrial function has not been demonstrated yet. Here, we evaluated the impact of three CQA-derivatives extracted from purple sweet potato, namely 5-CQA, 3,4- and 4,5-diCQA, on mitochondrial activity in primary hepatocytes using an extracellular flux analyzer. Notably, an increase of maximal respiration and spare respiratory capacity were observed when 5-CQA and 3,4-diCQA were added to the system indicating the improved mitochondrial function. Moreover, 3,4-diCQA was shown to considerably increase glycolytic reserve which is a measure of cell capability to respond to an energy demand through glycolysis. Conversely, 4,5-diCQA did not modify mitochondrial activity but increased glycolysis at low concentration in primary hepatocytes. All compounds tested improved cellular capacity to oxidize fatty acids. Overall, our results demonstrated the potential of test CQA-derivatives to modify mitochondrial function in hepatic cells. It is especially relevant in case of dysfunctional mitochondria in hepatocytes linked to hepatic steatosis during obesity, diabetes, and metabolic syndrome.
Asunto(s)
Hepatocitos/efectos de los fármacos , Ipomoea batatas/química , Mitocondrias/efectos de los fármacos , Extractos Vegetales/farmacología , Ácido Quínico/análogos & derivados , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Hepatocitos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ácido Quínico/química , Ácido Quínico/aislamiento & purificación , Ácido Quínico/farmacologíaRESUMEN
AbstractA new quinic acid derivative, 3-O-syringoylquinic acid methyl ester (1), along with eight known quinic acid derivatives (2-9), three coumarins (10-12), one phenylpropanoid (13), three feruloyltyramine derivatives (14-16), one lignan (17) and two isoflavones (18-19) were isolated from an ethyl acetate-soluble fraction of the roots and stems of Erycibe obtusifolia. The structure was elucidated on the basis of spectroscopic methods such as 1D and 2D-NMR, including HR-ESI-MS spectrometry. All of these compounds were investigated for their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and inhibitory effects on mushroom tyrosinase. Compounds 2-9, quinic acid derivatives with caffeoyl moiety, showed significant DPPH radical scavenging activity. Moreover, compounds 2 and 5-10 showed weak mushroom tyrosinase inhibitory effects.
Asunto(s)
Antioxidantes , Convolvulaceae/química , Ésteres/farmacología , Monofenol Monooxigenasa/antagonistas & inhibidores , Ácido Quínico/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Ésteres/aislamiento & purificación , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Raíces de Plantas/química , Tallos de la Planta/química , Ácido Quínico/aislamiento & purificaciónRESUMEN
Petasites japonicus have been used since a long time in folk medicine to treat diseases including plague, pestilential fever, allergy, and inflammation in East Asia and European countries. Bioactive compounds that may prevent and treat infectious diseases are identified based on their ability to inhibit bacterial neuraminidase (NA). We aimed to isolate and identify bioactive compounds from leaves and stems of P. japonicas (PJA) and elucidate their mechanisms of NA inhibition. Key bioactive compounds of PJA responsible for NA inhibition were isolated using column chromatography, their chemical structures revealed using 1 H NMR, 13 C NMR, DEPT, and HMBC, and identified to be bakkenolide B (1), bakkenolide D (2), 1,5-di-O-caffeoylquinic acid (3), and 5-O-caffeoylquinic acid (4). Of these, 3 exhibited the most potent NA inhibitory activity (IC50 = 2.3 ± 0.4 µM). Enzyme kinetic studies revealed that 3 and 4 were competitive inhibitors, whereas 2 exhibited non-competitive inhibition. Furthermore, a molecular docking simulation revealed the binding affinity of these compounds to NA and their mechanism of inhibition. Negative-binding energies indicated high proximity of these compounds to the active site and allosteric sites of NA. Therefore, PJA has the potential to be further developed as an antibacterial agent for use against diseases associated with NA.
Asunto(s)
Clostridium perfringens/enzimología , Inhibidores de Glicósido Hidrolasas/farmacología , Neuraminidasa/antagonistas & inhibidores , Petasites/química , Extractos Vegetales/farmacología , Ácido Quínico/análogos & derivados , Sesquiterpenos/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Cinética , Estructura Molecular , Neuraminidasa/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ácido Quínico/química , Ácido Quínico/aislamiento & purificación , Ácido Quínico/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificaciónRESUMEN
Hibiscus species (Malvaceae) have been long used as an antihypertensive folk remedy. The aim of our study was to specify the optimum solvent for extraction of the angiotensin-converting enzyme inhibiting (ACEI) constituents from Hibiscus sabdariffa L. The 80% methanol extract (H2) showed the highest ACEI activity, which exceeds that of the standard captopril (IC50 0.01255 ± 0.00343 and 0.210 ± 0.005 µg/mL, respectively). Additionally, in a comprehensive metabolomics approach, an ultra-performance liquid chromatography (UPLC) coupled to the high resolution tandem mass spectrometry (HRMS) method was used to trace the metabolites from each extraction method. Interestingly, our comprehensive analysis showed that the 80% methanol extract was predominated with secondary metabolites from all classes including flavonoids, anthocyanins, phenolic and organic acids. Among the detected metabolites, phenolic acids such as ferulic and chlorogenic acids, organic acids such as citrate derivatives and flavonoids such as kaempferol have been positively correlated to the antihypertensive potential. These results indicates that these compounds may significantly contribute synergistically to the ACE inhibitory activity of the 80% methanol extract.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/química , Antihipertensivos/química , Hibiscus/química , Extracción Líquido-Líquido/métodos , Metanol/química , Peptidil-Dipeptidasa A/química , Solventes/química , Inhibidores de la Enzima Convertidora de Angiotensina/aislamiento & purificación , Antihipertensivos/aislamiento & purificación , Ácido Clorogénico/química , Ácido Clorogénico/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Ácido Cítrico/química , Ácido Cítrico/aislamiento & purificación , Ácidos Cumáricos/química , Ácidos Cumáricos/aislamiento & purificación , Pruebas de Enzimas , Humanos , Quempferoles/química , Quempferoles/aislamiento & purificación , Metaboloma , Peptidil-Dipeptidasa A/metabolismo , Extractos Vegetales/química , Ácido Quínico/análogos & derivados , Ácido Quínico/química , Ácido Quínico/aislamiento & purificación , Metabolismo Secundario/fisiología , Soluciones , Relación Estructura-Actividad , Espectrometría de Masas en TándemRESUMEN
Chlorogenic (5-CQA), 1,5-, 3,5-, 4,5- and 3,4-dicaffeoylquinic (DCQA) acids were identified and quantified in the methanol extracts of Inula oculus-christi L., I. bifrons L., I. aschersoniana Janka var. aschersoniana, I. ensifolia L., I. conyza (Griess.) DC. and I. germanica L. by HPLC analysis. The amount of 5-CQA varied from 5.48 to 28.44â mg/g DE and the highest content was detected in I. ensifolia. 1,5-DCQA (4.05-55.25â mg/g DE) was the most abundant dicaffeoyl ester of quinic acid followed by 3,5-DCQA, 4,5-DCQA and 3,4-DCQA. The extract of I. ensifolia showed the highest total phenolic content (119.92±0.95â mg GAE/g DE) and exhibited the strongest DPPH radical scavenging activity (69.41±0.55 %). I. bifrons extract was found to be the most active sample against ABTS.+ (TEAC 0.257±0.012â mg/mL) and the best tyrosinase inhibitor. The studied extracts demonstrated a low inhibitory effect towards acetylcholinesterase and possessed low cytotoxicity in concentration range from 10 to 300â µg/mL toward non-cancer (MDCK II) and cancer (A 549) cells.
Asunto(s)
Acetilcolinesterasa/química , Antioxidantes/química , Inhibidores Enzimáticos/química , Inula/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Ácido Quínico/análogos & derivados , Acetilcolinesterasa/metabolismo , Animales , Bulgaria , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Perros , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Flores/química , Flores/metabolismo , Humanos , Inula/metabolismo , Células de Riñón Canino Madin Darby , Monofenol Monooxigenasa/metabolismo , Fenoles/química , Fenoles/aislamiento & purificación , Fenoles/farmacología , Extractos Vegetales/química , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Ácido Quínico/química , Ácido Quínico/aislamiento & purificación , Ácido Quínico/farmacologíaRESUMEN
Byproducts from artichoke represent the majority of the mass collected from the plant and constitute an interesting source of bioactive compounds such as inositols and caffeoylquinic acids. In this work, a microwave assisted extraction (MAE) methodology was developed for the simultaneous extraction of these compounds from artichoke stalks, leaves, receptacles and external bracts. Optimal MAE conditions to maximize the extraction of these bioactives and the antioxidant activity were 97 °C, 3 min, ethanol:water (50:50, v/v). Moreover, a GC-MS methodology was also developed for the simultaneous determination of these compounds in a single run; optimal derivatization conditions were achieved using hexamethyldisilazane and N,O-bis(trimethylsilyl)trifluoroacetamide with 1% trimethylchlorosilane. Artichoke receptacle extracts were the richest in caffeoylquinic acids (28-35 mg g-1 dry sample), followed by the bracts (9-18 mg g-1 dry sample), while those from leaves showed the highest concentrations of inositols (up to 15 mg g-1 dry sample). Receptacle extracts also had the highest antioxidant activity (123 mg TE g-1 dry sample) and the greatest concentration of total phenolic compounds (47 mg GAE g-1 dry sample). Therefore, the developed methodology could be considered as a valuable procedure to obtain and characterize bioactive ingredients with industrial interest from artichoke byproducts, opening new routes of revalorization of artichoke agro-industrial residues.
Asunto(s)
Cynara scolymus/química , Inositol/análisis , Microondas , Ácido Quínico/análogos & derivados , Antioxidantes/análisis , Cromatografía de Gases y Espectrometría de Masas , Inositol/aislamiento & purificación , Fenoles/análisis , Extractos Vegetales/química , Ácido Quínico/análisis , Ácido Quínico/aislamiento & purificaciónRESUMEN
Immature dendritic cells (iDCs) play very important roles in the pathological process of rheumatoid arthritis (RA). Therefore, it is urgent to search for natural products with antiproliferative activity on iDCs for anti-RA drug discovery. Erycibe schmidtii, a traditional Chinese medicine, has been used to treat RA in China. Its bioactive ingredients on RA are still unclear. In this study, twenty compounds including a new caffeoylquinic acid derivative, 3-O-caffeoyl-4-O-syringoylquinic acid methyl ester (16), were isolated from E. schmidtii. Their structures were elucidated by NMR and mass spectroscopic analysis, and comparison with literature data. Seventeen compounds were obtained from this plant for the first time, and ten were first found from the genus Erycibe. Scopoletin (1, 5.0 µM) functionally reduced proliferation level of bone marrow immature dendritic cells (BM-iDCs) more than 50%, relative to vehicle. However, scopoletin (1) exhibited no effect on the phagocytosis or survival of BM-iDCs in vitro.
Asunto(s)
Convolvulaceae/química , Células Dendríticas/efectos de los fármacos , Escopoletina/farmacología , Artritis Reumatoide/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , China , Células Dendríticas/citología , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Medicina Tradicional China/métodos , Estructura Molecular , Fagocitosis/efectos de los fármacos , Ácido Quínico/análogos & derivados , Ácido Quínico/aislamiento & purificación , Escopoletina/uso terapéuticoRESUMEN
Convolvulus trabutianus Schweinf. & Muschl. is an endemic plant from northern Sahara used in folk medicine. Herein we report, the isolation, characterization and evaluation of the radical scavenging properties of twenty three compounds from different extracts of this species by on-line HPLC-ABTSâ¢+ screening. These compounds include nine phenolic acids: 2, 6, 10-16, two phytosterols: 3-4, four coumarins: 5, 7-9, two quinic acids: 21 and 22 and six flavonoids: 1, 17-20 and 23 among which the most active were: 10, 16, 21 and 22. All the extracts showed a significant antioxidant activity on-line. These results were validated off-line by ORAC and TEAC assays. Four compounds: 1, 5, 18 and 19 were described for the first time from the Convolvulaceae family, whereas compounds 2, 6, 8, 10, 13 and 21 were new for the genus Convolvulus.
Asunto(s)
Antioxidantes/farmacología , Convolvulus/química , Evaluación Preclínica de Medicamentos/métodos , Polifenoles/farmacología , África del Norte , Antioxidantes/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , Flavonoides/análisis , Flavonoides/aislamiento & purificación , Hidroxibenzoatos , Extractos Vegetales/química , Plantas Medicinales/química , Polifenoles/aislamiento & purificación , Ácido Quínico/aislamiento & purificaciónRESUMEN
The seed of Hyptis suaveolens, commonly known as wild flour ball (san fen yuan) in Taiwan, serves as a main refreshing drink substance in several regions. This study investigated firstly its secondary metabolites, leading to the isolation of five major caffeoylquinic acid derivatives (1-5) from the ethanol extract. In addition, ten minors, including three caffeoylquinic acid derivatives (12-14), were characterized via assistance of HPLC-SPE-NMR. Of these isolates, sodium 4,5-dicaffeoylquinate (2) and methyl 3,5-dicaffeoylquinate (4) showed moderate inhibitory activity against xanthine oxidase with the respective IC50 values of 69.4 µM and 92.1 µM (c.f. allopurinol IC50 28.4 µM). Quantitative HPLC analysis of the EtOH extract indicates the content of sodium 3,5-dicaffeoylquinate (1) and sodium 4,5-dicaffeoylquinate (2) to be 0.1% and 0.08% (w/w, dry seed), respectively. This study not only discloses the bioactive constituents, but also demonstrates the potential of H. suaveolens seed as an antihyperuricemic nutraceutical.
Asunto(s)
Suplementos Dietéticos/análisis , Hiperuricemia/tratamiento farmacológico , Hyptis/química , Extractos Vegetales/uso terapéutico , Ácido Quínico/análogos & derivados , Semillas/química , Cromatografía Líquida de Alta Presión , Humanos , Hiperuricemia/metabolismo , Espectroscopía de Resonancia Magnética , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ácido Quínico/química , Ácido Quínico/aislamiento & purificación , Ácido Quínico/uso terapéutico , TaiwánRESUMEN
Morus alba L. is a medicinal plant that contains a high amount of caffeoylquinic acids such as 3-caffeoylquinic acid (3-CQA), 5-caffeoylquinic acid (5-CQA) and 4-caffeoylquinic acid (4-CQA). This study aimed to establish a fast and efficient method for separating caffeoylquinic acids from mulberry leaves by using high-speed countercurrent chromatography coupled with macroporous resin. D101 resin showed better adsorption and desorption capacity for three caffeoylquinic acids among six macroporous resin adsorbents. The contents of 3-CQA, 5-CQA and 4-CQA reached for 4.77%, 18.95% and 9.84% through one cycle of D101 resin, which were 3.13-fold, 4.57-fold and 4.78-fold more than those in crude extracts, respectively. With a two-phase solvent system of ethyl acetate-water (1:1, V/V), >93% purity of target compounds were obtained in one cycle during 150 min with the recovery yields of 80.59%, 99.56% and 94.21% for 3-CQA, 5-CQA and 4-CQA, respectively. The structural identification of target compounds was carried out by ESI-MS, 1H NMR and 13C NMR spectra. The present result represented an easy and efficient separation strategy for the utilization of mulberry resource.
Asunto(s)
Distribución en Contracorriente/métodos , Morus/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ácido Quínico/análogos & derivados , Extracción Líquido-Líquido , Espectrometría de Masas , Hojas de la Planta/química , Ácido Quínico/química , Ácido Quínico/aislamiento & purificaciónRESUMEN
BACKGROUND AND PURPOSE: Quinic acid (QA) is an abundant natural compound from plant sources which may improve metabolic health. However, little attention has been paid to its effects on pancreatic beta-cell functions, which contribute to the control of metabolic health by lowering blood glucose. Strategies targeting beta-cell signal transduction are a new approach for diabetes treatment. This study investigated the efficacy of QA to stimulate beta-cell function by targeting the basic molecular machinery of metabolism-secretion coupling. EXPERIMENTAL APPROACH: We measured bioenergetic parameters and insulin exocytosis in a model of insulin-secreting beta-cells (INS-1E), together with Ca2+ homeostasis, using genetically encoded sensors, targeted to different subcellular compartments. Islets from mice chronically infused with QA were also assessed. KEY RESULTS: QA triggered transient cytosolic Ca2+ increases in insulin-secreting cells by mobilizing Ca2+ from intracellular stores, such as endoplasmic reticulum. Following glucose stimulation, QA increased glucose-induced mitochondrial Ca2+ transients. We also observed a QA-induced rise of the NAD(P)H/NAD(P)+ ratio, augmented ATP synthase-dependent respiration, and enhanced glucose-stimulated insulin secretion. QA promoted beta-cell function in vivo as islets from mice infused with QA displayed improved glucose-induced insulin secretion. A diet containing QA improved glucose tolerance in mice. CONCLUSIONS AND IMPLICATIONS: QA modulated intracellular Ca2+ homeostasis, enhancing glucose-stimulated insulin secretion in both INS-1E cells and mouse islets. By increasing mitochondrial Ca2+ , QA activated the coordinated stimulation of oxidative metabolism, mitochondrial ATP synthase-dependent respiration, and therefore insulin secretion. Bioactive agents raising mitochondrial Ca2+ in pancreatic beta-cells could be used to treat diabetes.
Asunto(s)
Productos Biológicos/farmacología , Calcio/metabolismo , Secreción de Insulina/efectos de los fármacos , Células Secretoras de Insulina/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Ácido Quínico/farmacología , Actinidia/química , Animales , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Células Cultivadas , Café/química , Relación Dosis-Respuesta a Droga , Hippophae/química , Células Secretoras de Insulina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Prunus/química , Ácido Quínico/química , Ácido Quínico/aislamiento & purificación , Ratas , Relación Estructura-Actividad , Vaccinium macrocarpon/química , Vaccinium myrtillus/químicaRESUMEN
Twelve chlorogenic acid derivatives and two flavones were isolated from Moquiniastrum floribundum (Asteraceae, other name: Gochnatia floribunda). Compounds were evaluated in relation to their cytotoxicity and antiradical properties. Cytotoxicity was not observed for compounds, however, chlorogenic acid derivatives showed antiradical activity and were more active than the Trolox standard. Quinic acid esterified with caffeoyl group at C-4 position showed higher antiradical activity compared to acylation at C-3 or C-5 positions. Additional caffeoyl groups esterified in quinic acid increase the antiradical activity observed for 4-caffeoylquinic acid. Excepted to 3,4-dicaffeoylquinic acid methyl ester, methyl ester derivatives show higher capacity of trapping radicals than their respective acids. Consequently, the presence of caffeoyl group at C-4 position of quinic acid is suggested as fundamental to obtain the highest antiradical activity.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Asteraceae/química , Compuestos de Bifenilo/antagonistas & inhibidores , Picratos/antagonistas & inhibidores , Ácido Quínico/análogos & derivados , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células HCT116 , Humanos , Estructura Molecular , Ácido Quínico/química , Ácido Quínico/aislamiento & purificación , Ácido Quínico/farmacología , Relación Estructura-ActividadRESUMEN
When apples are processed into juices or ciders, a great variety of neoformed molecules are generated by enzymatic oxidation of polyphenols. These phenolic oxidation products could be responsible of specific organoleptic properties in apple juices and ciders. 5'-O-Caffeoylquinic acid (CQA) is the major hydroxycinnamic acid in apple and the preferential substrate of apple polyphenoloxidase (PPO). Its main oxidation products were synthetized and purified at the multi-milligrams scale to decipher their structures using mass spectrometry. CQA oxidation products were first synthetized in model solution by oxidizing CQA, in the presence of oxygen and PPO. Then, a specific method involving centrifugal partition chromatography (CPC) was developed to fractionate the main oxidation products corresponding to CQA dehydrodimers (MW 706 Da). For this purpose, CPC was performed in Elution-Extrusion Countercurrent Chromatography (EECCC) mode using a two-phase solvent system precisely selected according to the partition coefficient of the targeted compounds. After a last purification step using semi-preparative reversed phase HPLC, ten CQA dehydrodimers resulting from oxidative coupling were successfully purified, with a UV 280 nm chromatographic purity superior to 85%. Hypothetical structures were formulated for all CQA dehydrodimers based on their UV-vis, MS and MSn spectra. According to this study, centrifugal partition chromatography in combinaison with semi-preparative HPLC was a promising tool to fractionate or purify phenolic oxidation products.
Asunto(s)
Fraccionamiento Químico , Ácido Clorogénico/análogos & derivados , Distribución en Contracorriente , Análisis de los Alimentos/métodos , Espectrometría de Masas , Ácido Quínico/análogos & derivados , Ácido Clorogénico/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Malus/química , Oxidación-Reducción , Fenoles/metabolismo , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Ácido Quínico/aislamiento & purificaciónRESUMEN
Caffeoylquinic acid derivatives exhibit anti-inflammatory, antioxidant, and antibacterial activities. We successfully applied pH-zone-refining counter-current chromatography (pH-ZRCCC) to separation of isomeric caffeoylquinic acids from Lonicerae japonicae Flos using a two-phase solvent system composed of ethyl acetate-n-butanol-acetonitrile-water (3:1:1:5, v/v/v/v). Trifluoroacetic acid (10 mM) was added to the upper phase as a retainer and ammonium hydroxide (10 mM) was added to the lower phase as an eluter. As a result, 167.8 mg of chlorogenic acid, 15.9 mg of isochlorogenic acid B, 103.4 mg of isochlorogenic acid C, and 156.0 mg of isochlorogenic acid A were obtained from 1.2 g of crude extract, and all compound purities were over 96%. In addition, by comparing the numeric values of partition coefficient of compounds, it was found that larger differences between the K values of adjacent compounds in the solvent systems resulted in higher sample loading capacities. pH-ZRCCC method is an efficient preparative separation of isomeric caffeoylquinic acids from natural products.
Asunto(s)
Técnicas de Química Analítica/métodos , Distribución en Contracorriente , Extractos Vegetales/química , Ácido Quínico/análogos & derivados , Solventes/química , Acetonitrilos/química , Ácido Clorogénico/análogos & derivados , Ácido Clorogénico/química , Concentración de Iones de Hidrógeno , Lonicera , Ácido Quínico/aislamiento & purificaciónRESUMEN
The acidity and antioxidant activity of cold brew coffee were investigated using light roast coffees from Brazil, two regions of Ethiopia, Columbia, Myanmar, and Mexico. The concentrations of three caffeoylquinic acid (CQA) isomers were also determined. Cold brew coffee chemistry was compared to that of hot brew coffee prepared with the same grind-to-coffee ratio. The pH values of the cold and hot brew samples were found to be comparable, ranging from 4.85 to 5.13. The hot brew coffees were found to have higher concentrations of total titratable acids, as well as higher antioxidant activity, than that of their cold brew counterparts. It was also noted that both the concentration of total titratable acids and antioxidant activity correlated poorly with total CQA concentration in hot brew coffee. This work suggests that the hot brew method tends to extract more non-deprotonated acids than the cold brew method. These acids may be responsible for the higher antioxidant activities observed in the hot brew coffee samples.
Asunto(s)
Ácidos/química , Antioxidantes/química , Café/química , Ácido Quínico/análogos & derivados , Antioxidantes/aislamiento & purificación , Brasil , Ácido Clorogénico/química , Etiopía , Calor , Humanos , Concentración de Iones de Hidrógeno , México , Mianmar , Ácido Quínico/química , Ácido Quínico/aislamiento & purificación , Semillas/químicaRESUMEN
An effective method based on the combined homogenate-assisted high-pressure disruption extraction (HHPDE) was applied to the extraction and determination of the main phenolic acid compounds from Lonicerae Japonicae Flos. The optimized HHPDE showed competitive advantage in yield (The extraction yields of NCA, CA, 3,5DCA and 4,5DCA in HHPDE were 1.21, 1.08, 1.06 and 1.17 fold higher than those in UAE), time-saving (<5â¯min) and relative low temperature requirement (4-16⯰C) compared to HRE and UAE. Furthermore, the HHPDE method behaved a good repeatability and reproducibility according to the HPLC. The mentioned HHPDE method is firstly applied in the extraction and quantification of neochlorogenic acid chlorogenic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid in Lonicerae Japonicae Flos. This work provided an excellent alternative for the extraction and quantification of thermosensitive from plants.