RESUMO
Oxidative stress exerts multiple disruptive effects on cellular morphology and function and is a major detriment to age-related and pathological neurodegenerative processes. The present study introduces an evaluative and comparative investigation of the antioxidant and cytoprotective properties of a Prenanthes purpurea extract and its major constituent 3,5-dicaffeoylquinic acid (DiCQA) in an in vitro model of H2O2-induced neurotoxicity. Using validated in vitro and in silico approaches, we established the presence and concentration dynamics of cellular protection in a 24 h pretreatment regimen with the natural products. The conducted cytotoxicity studies and the automated Chou-Talalay analysis for studying drug interactions demonstrated a strong antagonistic effect of the tested substances against oxidative stimuli in an "on demand" manner, prevailing at the higher end of the concentration range. These findings were further supported by the proteomic characterization of the treatment samples, accounting for a more distinct neuroprotection provided by the pure polyphenol 3,5-DiCQA.
Assuntos
Peróxido de Hidrogênio , Estresse Oxidativo , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antioxidantes/farmacologia , Antioxidantes/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Humanos , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Ácido Quínico/química , Ácido Clorogênico/farmacologia , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/química , Animais , Sobrevivência Celular/efeitos dos fármacosRESUMO
Polyphenolic compounds are common constituents of human and animal diets and undergo extensive metabolism by the gut microbiota before entering circulation. In order to compare the transformations of polyphenols from yerba mate, rosemary, and green tea extracts in the gastrointestinal tract, simulated gastrointestinal digestion coupled with colonic fermentation were used. For enhancing the comparative character of the investigation, colonic fermentation was performed with human, pig and rat intestinal microbiota. Chemical analysis was performed using a HPLC system coupled to a diode-array detector and mass spectrometer. Gastrointestinal digestion diminished the total amount of phenolics in the rosemary and green tea extracts by 27.5 and 59.2 %, respectively. These reductions occurred mainly at the expense of the major constituents of these extracts, namely rosmarinic acid (-45.7 %) and epigalocatechin gallate (-60.6 %). The yerba mate extract was practically not affected in terms of total phenolics, but several conversions and isomerizations occurred (e.g., 30 % of trans-3-O-caffeoylquinic acid was converted into the cis form). The polyphenolics of the yerba mate extract were also the least decomposed by the microbiota of all three species, especially in the case of the human one (-10.8 %). In contrast, the human microbiota transformed the polyphenolics of the rosemary and green extracts by 95.9 and 88.2 %, respectively. The yerba mate-extract had its contents in cis 3-O-caffeoylquinic acid diminished by 78 % by the human microbiota relative to the gastrointestinal digestion, but the content of 5-O-caffeoylquinic acid (also a chlorogenic acid), was increased by 22.2 %. The latter phenomenon did not occur with the rat and pig microbiota. The pronounced interspecies differences indicate the need for considerable caution when translating the results of experiments on the effects of polyphenolics performed in rats, or even pigs, to humans.
Assuntos
Colo , Depsídeos , Digestão , Fermentação , Ilex paraguariensis , Extratos Vegetais , Polifenóis , Ácido Rosmarínico , Rosmarinus , Animais , Humanos , Extratos Vegetais/metabolismo , Rosmarinus/química , Ratos , Ilex paraguariensis/química , Suínos , Depsídeos/metabolismo , Depsídeos/análise , Polifenóis/metabolismo , Polifenóis/análise , Colo/metabolismo , Colo/microbiologia , Masculino , Cinamatos/metabolismo , Cinamatos/análise , Microbioma Gastrointestinal , Chá/química , Ácido Quínico/análogos & derivados , Ácido Quínico/metabolismo , Ácido Quínico/análise , Catequina/análogos & derivados , Catequina/metabolismo , Catequina/análise , Cromatografia Líquida de Alta Pressão , Camellia sinensis/químicaRESUMO
As the main coffee polyphenols, caffeoylquinic acids (CQAs) are abundant in coffee-derived products and have the potential to act as novel feed additives for animals. However, research on the side effects of dietary CQAs supplementation is scarce, especially in young animals. Here, we explore the safety of CQAs derived from green coffee beans. Results showed that ingesting 50, 125, 250, and 500 mg/kg of dietary CQAs for 55 days is associated with greater final body weight, average daily gain, and feed efficiency in piglets compared with the control group (P < 0.05). CQAs also increased the apparent digestibility of dry matter, crude protein, and gross energy at a dose over 50 mg/kg (P < 0.05). Interestingly, CQAs supplementation with 500 mg/kg increased the white blood cell count (P < 0.05). Moreover, CQAs supplementation at a dose over 50 mg/kg decreased the serum total cholesterol concentration but increased the immunoglobulin M level in serum (P < 0.05). Importantly, CQAs supplementation had no side effects on organ histopathology and organ weight (P > 0.05). These results suggest that CQAs could serve as a secure and effective additive to improve growth performance without negatively affecting the organs of piglets.
Assuntos
Ração Animal , Coffea , Café , Polifenóis , Ácido Quínico , Animais , Ácido Quínico/análogos & derivados , Ácido Quínico/análise , Polifenóis/administração & dosagem , Polifenóis/química , Suínos/metabolismo , Ração Animal/análise , Coffea/química , Café/química , Suplementos Nutricionais/análise , Masculino , Feminino , Peso Corporal/efeitos dos fármacosRESUMO
BACKGROUND: Chrysanthemum morifolium 'HangBaiJu', a popular medicinal and edible plant, exerts its biological activities primarily through the presence of flavones and caffeoylquinic acids (CQAs). However, the regulatory mechanism of flavone and CQA biosynthesis in the chrysanthemum capitulum remains unclear. RESULTS: In this study, the content of flavones and CQAs during the development of chrysanthemum capitulum was determined by HPLC, revealing an accumulation pattern with higher levels at S1 and S2 and a gradual decrease at S3 to S5. Transcriptomic analysis revealed that CmPAL1/2, CmCHS1/2, CmFNS, CmHQT, and CmHCT were key structural genes in flavones and CQAs biosynthesis. Furthermore, weighted gene co-expression correlation network analysis (WGCNA), k-means clustering, correlation analysis and protein interaction prediction were carried out in this study to identify transcription factors (TFs) associated with flavone and CQA biosynthesis, including MYB, bHLH, AP2/ERF, and MADS-box families. The TFs CmERF/PTI6 and CmCMD77 were proposed to act as upstream regulators of CmMYB3 and CmbHLH143, while CmMYB3 and CmbHLH143 might form a complex to directly regulate the structural genes CmPAL1/2, CmCHS1/2, CmFNS, CmHQT, and CmHCT, thereby controlling flavone and CQA biosynthesis. CONCLUSIONS: Overall, these findings provide initial insights into the TF regulatory network underlying flavones and CQAs accumulation in the chrysanthemum capitulum, which laid a theoretical foundation for the quality improvement of C. morifolium 'HangBaiJu' and the high-quality development of the industry.
Assuntos
Chrysanthemum , Flavonas , Ácido Quínico , Chrysanthemum/genética , Chrysanthemum/metabolismo , Flavonas/metabolismo , Ácido Quínico/metabolismo , Ácido Quínico/análogos & derivados , Regulação da Expressão Gênica de Plantas , Perfilação da Expressão Gênica , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Metabolômica , TranscriptomaRESUMO
Despite the development of several anticancer treatments, there remains a need for new drugs that can overcome resistance and reduce side effects. While the medicinal herb Hydrocotyle umbellata (H. umbellata) has been used to relieve pain and inflammation, its antitumor properties have not yet been explored. In this study, we investigated the anticarcinogenic potential of H. umbellata extract (HUE) and its major components, as well as the underlying molecular mechanisms. Our results showed that HUE inhibited the growth of various tumor cell lines, including B16F10, without affecting non-cancer cells. Furthermore, HUE was effective in treating and preventing tumor growth in mice. Our mechanistic studies revealed that HUE inhibited cellular respiration, thereby reducing tumor cell proliferation. When combined with 2-deoxy-D-glucose, HUE demonstrated an enhanced anticancer effect by increasing the rate apoptosis. Analysis of the ethyl acetate and n-butanol fractions of HUE identified 1,3,4-trihydroxy-2-butanyl-α-d-glucopyranoside and caffeoylquinic acid derivatives as the major components responsible for the observed anticancer effects. In conclusion, our findings suggest that HUE and its two major components have the potential to be developed as effective therapeutic agents for a wide range of tumors by targeting cancer cell metabolism.
Assuntos
Antineoplásicos Fitogênicos , Apoptose , Proliferação de Células , Extratos Vegetais , Animais , Extratos Vegetais/farmacologia , Camundongos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Humanos , Proliferação de Células/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Anticarcinógenos/farmacologia , Camundongos Endogâmicos C57BL , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologiaRESUMO
With the increasing of aging population and the consumption of high-fat diets (HFD), the incidence of Alzheimer's disease (AD) has skyrocketed. Natural antioxidants show promising potential in the prevention of AD, as oxidative stress and neuroinflammation are two hallmarks of AD pathogenesis. Here, we showed that quinic acid (QA), a polyphenol derived from millet, significantly decreased HFD-induced brain oxidative stress and neuroinflammation and the levels of Aß and p-Tau. Examination of gut microbiota suggested the improvement of the composition of gut microbiota in HFD mice after QA treatment. Metabolomic analysis showed significant increase of gut microbial tryptophan metabolites indole-3-acetic acid (IAA) and kynurenic acid (KYNA) by QA. In addition, IAA and KYNA showed negative correlation with pro-inflammatory factors and AD indicators. Further experiments on HFD mice proved that IAA and KYNA could reproduce the effects of QA that suppress brain oxidative stress and inflammation and decrease the levels of of Aß and p-Tau. Transcriptomics analysis of brain after IAA administration revealed the inhibition of DR3/IKK/NF-κB signaling pathway by IAA. In conclusion, this study demonstrated that QA could counteract HFD-induced brain oxidative stress and neuroinflammation by regulating inflammatory DR3/IKK/NF-κB signaling pathway via gut microbial tryptophan metabolites.
Assuntos
Encéfalo , Dieta Hiperlipídica , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , NF-kappa B , Estresse Oxidativo , Ácido Quínico , Transdução de Sinais , Triptofano , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Triptofano/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Ácido Quínico/metabolismo , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/prevenção & controle , Quinase I-kappa B/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/prevenção & controle , Ácidos Indolacéticos/metabolismo , Ácido Cinurênico/metabolismo , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/prevenção & controleRESUMO
BACKGROUND: 3,4,5-tri-O-caffeoylquinic acid (3,4,5-TCQA), a natural polyphenolic acid, has been shown to be effective against influenza A virus (IAV) infection. Although it was found to inhibit the neuraminidase of IAV, it may also perturb other cellular functions, as polyphenolic acids have shown antioxidant, anti-inflammatory and other activities. PURPOSE: This study aimed to investigate the effect of 3,4,5-TCQA at a cell level, which is critical for protecting host cell from IAV infection. STUDY DESIGN AND METHODS: We explored the effect of 3,4,5-TCQA on H292 cells infected or un-infected with Pr8 IAV. The major genes and related pathway were identified through RNA sequencing. The pathway was confirmed by qRT-PCR and western blot analysis. The anti-inflammatory activity was evaluated using nitric oxide measurement assay. RESULTS: We showed that 3,4,5-TCQA downregulated the immune response in H292 cells, and reduced the cytokine production in Pr8-infected cells, through Toll-like receptor (TLR) signaling pathway. In addition, 3,4,5-TCQA showed anti-inflammatory activity in LPS-activated RAW264.7 cells. CONCLUSION: Collectively, our results indicated that 3,4,5-TCQA suppressed inflammation caused by IAV infection through TLR3/7 signaling pathway. This provides a new insight into the antiviral mechanism of 3,4,5-TCQA.
Assuntos
Anti-Inflamatórios , Vírus da Influenza A , Ácido Quínico , Transdução de Sinais , Receptor 3 Toll-Like , Transdução de Sinais/efeitos dos fármacos , Humanos , Vírus da Influenza A/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Animais , Receptor 3 Toll-Like/metabolismo , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Receptor 7 Toll-Like/metabolismo , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Camundongos , Óxido Nítrico/metabolismo , Antivirais/farmacologia , Ácido Clorogênico/farmacologia , Ácido Clorogênico/análogos & derivadosRESUMO
In this study, chitosan low molecular weight (LCH) and chitosan medium molecular weight (MCH) were employed to encapsulate a yarrow extract rich in chlorogenic acid and dicaffeoylquinic acids (DCQAs) that showed antiproliferative activity against colon adenocarcinoma cells. The design of CH micro/nanoparticles to increase the extract colon delivery was carried out by using two different techniques: ionic gelation and spray drying. Ionic gelation nanoparticles obtained were smaller and presented higher yields values than spray-drying microparticles, but spray-drying microparticles showed the best performance in terms of encapsulation efficiency (EE) (> 94%), also allowing the inclusion of a higher quantity of extract. Spray-drying microparticles designed using LCH with an LCH:extract ratio of 6:1 (1.25 mg/mL) showed a mean diameter of 1.31 ± 0.21 µm and EE values > 93%, for all phenolic compounds studied. The release profile of phenolic compounds included in this formulation, at gastrointestinal pHs (2 and 7.4), showed for most of them a small initial release, followed by an increase at 1 h, with a constant release up to 3 h. Chlorogenic acid presented the higher release values at 3 h (56.91% at pH 2; 44.45% at pH 7.4). DCQAs release at 3 h ranged between 9.01- 40.73%, being higher for 1,5- and 3,4-DCQAs. After gastrointestinal digestion, 67.65% of chlorogenic and most DCQAs remained encapsulated. Therefore, spray-drying microparticles can be proposed as a promising vehicle to increase the colon delivery of yarrow phenolics compounds (mainly chlorogenic acid and DCQAs) previously described as potential agents against colorectal cancer.
Assuntos
Achillea , Proliferação de Células , Quitosana , Ácido Clorogênico , Neoplasias Colorretais , Nanopartículas , Tamanho da Partícula , Extratos Vegetais , Quitosana/química , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Achillea/química , Ácido Clorogênico/farmacologia , Ácido Clorogênico/administração & dosagem , Ácido Clorogênico/química , Nanopartículas/química , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Linhagem Celular Tumoral , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Ácido Quínico/química , Ácido Quínico/administração & dosagem , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Colo/efeitos dos fármacos , Colo/metabolismo , Portadores de Fármacos/química , Peso MolecularRESUMO
Dicaffeoyltartaric acid (diCT) and 3,5-dicaffeoylquinic acid (3,5-diCQ) are described for their aphicidal properties on several aphid species. Intending to valorize diCT and 3,5-diCQ as biocontrol products and because of the high adaptive capacities of aphids to xenobiotics, we sought to determine the existence of adaptation first in Myzus persicae (Sulzer) (Hemiptera: Aphididae) and then other aphids. Resistance of aphids to these biopesticides could be promoted by (i) the existence of resistance to synthetic insecticides that may confer cross-resistance and (ii) the presence of these compounds in wild plants likely which may have led to pre-existing adaptation in aphids. We assessed the resistance levels to diCT and 3,5-diCQ in 7 lab strains (including some resistant to synthetic aphicides) and 7 wild populations of M. persicae using biotests. The activities of detoxification enzymes contributing to insecticide resistance were also measured. Additionally, we followed the same method to characterize susceptibility to these caffeic derivatives in wild populations of Nasonovia ribisnigri (Mosley) (Hemiptera: Aphididae), Brevicoryne brassicae(Linnaeus) (Hemiptera: Aphididae) and, Aphis craccivora(Koch) (Hemiptera: Aphididae). Our results show variability in susceptibility to diCT between populations of M. persicae, but resistance ratios (RR) were low (RRâ =â 3.59). We found no cross-resistance between synthetic insecticides and diCT. Carboxylesterase and glutathione-S-transferase did not seem to be involved in its detoxification. A clone of A. craccivora collected from peanut, a species rich in diCT, was not susceptible to either diCT or 3,5-diCQ, suggesting a common molecular target for these 2 molecules and the existence of a high-effect resistance mechanism. These active botanical substances remain good candidates for M. persicae biocontrol in agriculture.
Assuntos
Afídeos , Ácidos Cafeicos , Resistência a Inseticidas , Inseticidas , Afídeos/efeitos dos fármacos , Animais , Inseticidas/farmacologia , Ácidos Cafeicos/farmacologia , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , SuccinatosRESUMO
Alzheimer's disease (AD) remains a challenging neurodegenerative disorder with limited therapeutic success. Traditional Chinese Medicine (TCM), as a promising new source for AD, still requires further exploration to understand its complex components and mechanisms. Here, focused on addressing Aß (1-40) aggregation, a hallmark of AD pathology, we employed a Thioflavin T fluorescence labeling method for screening the active molecular library of TCM which we established. Among the eight identified, 1,3-di-caffeoylquinic acid emerged as the most promising, exhibiting a robust binding affinity with a KD value of 26.7 nM. This study delves into the molecular intricacies by utilizing advanced techniques, including two-dimensional (2D) 15N-1H heteronuclear single quantum coherence nuclear magnetic resonance (NMR) and molecular docking simulations. These analyses revealed that 1,3-di-caffeoylquinic acid disrupts Aß (1-40) self-aggregation by interacting with specific phenolic hydroxyl and amino acid residues, particularly at Met-35 in Aß (1-40). Furthermore, at the cellular level, the identified compounds, especially 1,3-di-caffeoylquinic acid, demonstrated low toxicity and exhibited therapeutic potential by regulating mitochondrial membrane potential, reducing cell apoptosis, and mitigating Aß (1-40)-induced cellular damage. This study presents a targeted exploration of catechol compounds with implications for effective interventions in AD and sheds light on the intricate molecular mechanisms underlying Aß (1-40) aggregation disruption.
Assuntos
Peptídeos beta-Amiloides , Simulação de Acoplamento Molecular , Ácido Quínico , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Ácido Quínico/química , Humanos , Fragmentos de Peptídeos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Agregados Proteicos/efeitos dos fármacosRESUMO
(1) Background: Phytochemicals are crucial antioxidants that play a significant role in preventing cancer. (2) Methods: We explored the use of methyl jasmonate (MeJA) in the in vitro cultivation of D. morbifera adventitious roots (DMAR) and evaluated its impact on secondary metabolite production in DMAR, optimizing concentration and exposure time for cost-effectiveness. We also assessed its anti-inflammatory and anti-lung cancer activities and related gene expression levels. (3) Results: MeJA treatment significantly increased the production of the phenolic compound 3,5-Di-caffeoylquinic acid (3,5-DCQA). The maximum 3,5-DCQA production was achieved with a MeJA treatment at 40 µM for 36 h. MeJA-DMARE displayed exceptional anti-inflammatory activity by inhibiting the production of nitric oxide (NO) and reactive oxygen species (ROS) in LPS-induced RAW 264.7 cells. Moreover, it downregulated the mRNA expression of key inflammation-related cytokines. Additionally, MeJA-DMARE exhibited anti-lung cancer activity by promoting ROS production in A549 lung cancer cells and inhibiting its migration. It also modulated apoptosis in lung cancer cells via the Bcl-2 and p38 MAPK pathways. (4) Conclusions: MeJA-treated DMARE with increased 3,5-DCQA production holds significant promise as a sustainable and novel material for pharmaceutical applications thanks to its potent antioxidant, anti-inflammatory, and anti-lung cancer properties.
Assuntos
Acetatos , Anti-Inflamatórios , Ciclopentanos , Neoplasias Pulmonares , Oxilipinas , Raízes de Plantas , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Acetatos/farmacologia , Acetatos/química , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Humanos , Células RAW 264.7 , Raízes de Plantas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Óxido Nítrico/metabolismo , Apoptose/efeitos dos fármacos , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Ácido Quínico/química , Células A549 , Sapindaceae/químicaRESUMO
Herbal infusions exhibit diverse pharmacological effects, such as antioxidant, anti-inflammatory, anticancer, antihypertensive, and antineurodegenerative activities, which can be attributed to the high content of phenolic compounds (e.g., caffeoylquinic acids (CQAs)). In this study, we used ultraperformance liquid chromatography to determine the content of CQAs in the methanolic extracts of model herbs, namely, yerba mate (Ilex paraguariensis), stevia (Stevia rebaudiana), and Indian camphorweed (Pluchea indica (L.) Less.). The results revealed that yerba mate had the highest total CQA content (108.05 ± 1.12 mg/g of dry weight). Furthermore, we evaluated the effect of brewing conditions and storage at 4 °C under dark and light conditions on the antioxidant property and total phenolic and CQA contents of a yerba mate infusion. The analysis of the yerba mate infusions prepared with different steeping times, dried leaf weights, and water temperatures revealed that the amount of extracted CQAs was maximized (â¼175 mg/150 mL) when 6 g of dried leaves were steeped in hot water for 10 min. A total of 10-day refrigerated storage resulted in no significant changes in the antioxidant activity and total phenolic and CQA contents of an infusion kept in a brown container (dark). However, the antioxidant properties and total phenolic and CQA contents were negatively affected when kept in a clear container, suggesting the detrimental effect of light exposure. Our study provides practical recommendations for improving the preparation and storage of herbal infusions, thus catering to the needs of consumers, food scientists, and commercial producers. Moreover, it is the first study of the influence of light exposure on the content of crucial quality attributes within plant-based beverages.
Assuntos
Antioxidantes , Ilex paraguariensis , Extratos Vegetais , Ácido Quínico , Stevia , Ilex paraguariensis/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ácido Quínico/análogos & derivados , Ácido Quínico/análise , Stevia/química , Antioxidantes/farmacologia , Antioxidantes/análise , Fenóis/análise , Temperatura Baixa , Folhas de Planta/química , Armazenamento de MedicamentosRESUMO
Plant in vitro cultures can be an effective tool in obtaining desired specialized metabolites. The purpose of this study was to evaluate the effect of light-emitting diodes (LEDs) on phenolic compounds in Rhaponticum carthamoides shoots cultured in vitro. R. carthamoides is an endemic and medicinal plant at risk of extinction due to the massive harvesting of its roots and rhizomes from the natural environment. The shoots were cultured on an agar-solidified and liquid-agitated Murashige and Skoog's medium supplemented with 0.1 mg/L of indole-3-acetic acid (IAA) and 0.5 mg/L of 6-benzyladenine (BA). The effect of the medium and different treatments of LED lights (blue (BL), red (RL), white (WL), and a combination of red and blue (R:BL; 7:3)) on R. carthamoides shoot growth and its biosynthetic potential was observed. Medium type and the duration of LED light exposure did not affect the proliferation rate of shoots, but they altered the shoot morphology and specialized metabolite accumulation. The liquid medium and BL light were the most beneficial for the caffeoylquinic acid derivatives (CQAs) production, shoot growth, and biomass increment. The liquid medium and BL light enhanced the content of the sum of all identified CQAs (6 mg/g DW) about three-fold compared to WL light and control, fluorescent lamps. HPLC-UV analysis confirmed that chlorogenic acid (5-CQA) was the primary compound in shoot extracts regardless of the type of culture and the light conditions (1.19-3.25 mg/g DW), with the highest level under R:BL light. BL and RL lights were equally effective. The abundant component was also 3,5-di-O-caffeoylquinic acid, accompanied by 4,5-di-O-caffeoylquinic acid, a tentatively identified dicaffeoylquinic acid derivative, and a tricaffeoylquinic acid derivative 2, the contents of which depended on the LED light conditions.
Assuntos
Flavonoides , Luz , Brotos de Planta , Ácido Quínico , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Brotos de Planta/química , Ácido Quínico/análogos & derivados , Ácido Quínico/metabolismo , Ácido Quínico/química , Flavonoides/metabolismo , Flavonoides/química , Ácidos Indolacéticos/metabolismoRESUMO
Excessive accumulation of advanced glycation end products (AGEs) in the body is associated with diabetes and its complications. In this study, we aimed to explore the potential and mechanism of coffee leaf extract (CLE) in inhibiting the generation of AGEs and their precursors in an in vitro glycation model using bovine serum albumin and glucose (BSA-Glu) for the first time. High-performance liquid chromatography analysis revealed that CLE prepared with ultrasound pretreatment (CLE-U) contained higher levels of trigonelline, mangiferin, 3,5-dicaffeoylquinic acid, and γ-aminobutyric acid than CLE without ultrasound pretreatment (CLE-NU). The concentrations of these components, along with caffeine and rutin, were dramatically decreased when CLE-U or CLE-NU was incubated with BSA-Glu reaction mixture. Both CLE-U and CLE-NU exhibited a dose-dependent inhibition of fluorescent AGEs, carboxymethyllysine, fructosamine, 5-hydroxymethylfurfural, 3-deoxyglucosone, glyoxal, as well as protein oxidation products. Notably, CLE-U exhibited a higher inhibitory capacity compared to CLE-NU. CLE-U effectively quenched fluorescence intensity and increased the α-helix structure of the BSA-Glu complex. Molecular docking results suggested that the key bioactive compounds present in CLE-U interacted with the arginine residues of BSA, thereby preventing its glycation. Overall, this research sheds light on the possible application of CLE as a functional ingredient in combating diabetes by inhibiting the generation of AGEs.
Assuntos
Produtos Finais de Glicação Avançada , Extratos Vegetais , Folhas de Planta , Soroalbumina Bovina , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Soroalbumina Bovina/química , Coffea/química , Alcaloides/farmacologia , Furaldeído/análogos & derivados , Furaldeído/farmacologia , Frutosamina , Cromatografia Líquida de Alta Pressão , Glioxal , Glucose/metabolismo , Simulação de Acoplamento Molecular , Glicosilação/efeitos dos fármacos , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Rutina/farmacologia , Lisina/análogos & derivados , Cafeína/farmacologia , Desoxiglucose/análogos & derivados , Desoxiglucose/farmacologia , XantonasRESUMO
The industrial processing of pineapples generates a substantial quantity of by-products, including shell, crown, and core. Bromelain, a proteolytic enzyme found naturally in pineapple, including its by-products, may positively influence the bioaccessibility of phenolics from milk coffee. Therefore, this study aimed to assess how the inclusion of extracts from pineapple by-products, namely shell, crown and core, could impact the bioaccessibility of coffee phenolics when combined with milk. After measuring the proteolytic activity of pineapple by-products, the standardized in vitro digestion model of INFOGEST was employed to evaluate changes in total phenolic content, total antioxidant capacity, and individual phenolic compounds in different coffee formulations. The results showed that incorporating extracts from the crown or core in both black and milk coffee increased the bioaccessibility of total phenolics (from 93 to 114% to 105-129%) and antioxidants (from 54 to 56% to 84-87%), while this effect was not observed for the shell. Moreover, adding core extracts also enhanced the bioaccessibility of caffeoylquinic acids and gallic acid in milk coffee (from 0.72 to 0.85% and 109-155%, respectively). Overall, the findings of this study highlight that bromelain from pineapple core may have a favorable effect on the recovery of phenolic compounds in milk coffee, possibly due to its ability to cleave proteins. These outcomes point out that industrial by-products can be transformed into economic value by being reintroduced into the production process through suitable treatment instead of disposal.
Assuntos
Ananas , Antioxidantes , Café , Leite , Fenóis , Ananas/química , Fenóis/análise , Antioxidantes/análise , Café/química , Leite/química , Bromelaínas , Animais , Ácido Gálico/análise , Digestão , Disponibilidade Biológica , Extratos Vegetais/química , Ácido Quínico/análogos & derivados , Ácido Quínico/análise , Manipulação de Alimentos/métodosRESUMO
The present work carries out a quantitative analysis of the major bioactive compounds found in the native Mexican purple tomatoes. Total phenolic content ranged from 7.54 to 57.79 mg TPC/g DM, total flavonoid content ranged from 1.89 to 16.93 mg TFC/g DM, total anthocyanin content ranged from 0.29 to 2.56 mg TAC/g DM, and total carotenoid content ranged from 0.11 to 0.75 mg TCC/ g DM. In addition, 14 phenolic acids were identified, among which caffeoylquinic acid derivatives were the most abundant compounds with chlorogenic acid concentration up to 9.680 mg/g DM, together with flavonoids, such as rutin and quercetin-hexoxide. The qualitative analysis also showed the presence of 9 acylated anthocyanins and 2 carotenoids with significant functional features. As for anthocyanins, their chemical structures disclosed special structural features: glycosylated anthocyanins exhibited cis-trans hydroxycinnamic moieties and petunidin-3-(trans-p-coumaroyl)-rutinoside-5-glucoside was reported to be the main anthocyanin, whitin the range of concentrations between 0.160 and 1.143 mg/g DM.
Assuntos
Antocianinas , Carotenoides , Flavonoides , Fenóis , Solanum lycopersicum , Solanum lycopersicum/química , Antocianinas/análise , Carotenoides/análise , México , Flavonoides/análise , Fenóis/análise , Frutas/química , Ácido Clorogênico/análise , Ácido Quínico/análise , Ácido Quínico/análogos & derivados , Hidroxibenzoatos/análiseRESUMO
Caffeioyl quinic acids and polysaccharides from Artemisia selengensis Turcz are considered potential bioactive substances for hyperuricemia (HUA) treatment. While the mechanism of multi-component combined intervention of polysaccharides and dicaffeoylquinic acids (diCQAs) is not yet clear. In this study, we investigated the effect of A. selengensis Turcz leaves polysaccharides (APS) on the HUA treatment with diCQAs in vitro by direct inhibition of XOD activities and in vivo by using animal model. The results showed that APS had almost no inhibitory effect on XOD activities in vitro, but the inhibitory activity of diCQAs on XOD was affected by changes in inhibition type and inhibition constant. Compared to APS and diCQAs alone, high-dose APS and diCQAs in combination (ADPSh) could significantly reduce the production of uric acid (16.38 % reduction compared to diCQAs group) and oxidative stress damage. Additionally, this combined therapy showed promise in restoring the gut microbiota balance and increasing the short-chain fatty acids levels. The results suggested that APS and diCQAs in combination could be a potential inhibitor for HUA treatment.
Assuntos
Artemisia , Hiperuricemia , Folhas de Planta , Polissacarídeos , Artemisia/química , Folhas de Planta/química , Hiperuricemia/tratamento farmacológico , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Ácido Quínico/química , Estresse Oxidativo/efeitos dos fármacos , Masculino , Ácido Úrico , Microbioma Gastrointestinal/efeitos dos fármacos , Ratos , CamundongosRESUMO
Background: Caffeoylquinic acid (CQA), which is abundant in coffee beans and Centella asiatica, reportedly improves cognitive function in Alzheimer's disease (AD) model mice, but its effects on neuroinflammation, neuronal loss, and the amyloid-ß (Aß) plaque burden have remained unclear. Objective: To assess the effects of a 16-week treatment with CQA on recognition memory, working memory, Aß levels, neuronal loss, neuroinflammation, and gene expression in the brains of 5XFAD mice, a commonly used mouse model of familial AD. Methods: 5XFAD mice at 7 weeks of age were fed a 0.8% CQA-containing diet for 4 months and then underwent novel object recognition (NOR) and Y-maze tests. The Aß levels and plaque burden were analyzed by enzyme-linked immunosorbent assay and immunofluorescent staining, respectively. Immunostaining of markers of mature neurons, synapses, and glial cells was analyzed. AmpliSeq transcriptome analysis and quantitative reverse-transcription-polymerase chain reaction were performed to assess the effect of CQA on gene expression levels in the cerebral cortex of the 5XFAD mice. Results: CQA treatment for 4 months improved recognition memory and ameliorated the reduction of mature neurons and synaptic function-related gene mRNAs. The Aß levels, plaque burden, and glial markers of neuroinflammation seemed unaffected. Conclusions: These findings suggest that CQA treatment mitigates neuronal loss and improves cognitive function without reducing Aß levels or neuroinflammation. Thus, CQA is a potential therapeutic compound for AD, improving cognitive function via as-yet unknown mechanisms independent of reductions in Aß or neuroinflammation.
Assuntos
Disfunção Cognitiva , Modelos Animais de Doenças , Camundongos Transgênicos , Neurônios , Placa Amiloide , Ácido Quínico , Animais , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Ácido Quínico/uso terapêutico , Camundongos , Placa Amiloide/tratamento farmacológico , Placa Amiloide/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacosRESUMO
Few sclerophyllous plants from the central coast of Chile have been systematically studied. This work describes the phytochemical composition and antimicrobial properties of Baccharis concava Pers. (sin. B. macraei), a shrub found in the first line and near the Pacific coast. B. concava has been traditionally used by indigenous inhabitants of today's central Chile for its medicinal properties. Few reports exist regarding the phytochemistry characterization and biological activities of B. concava. A hydroalcoholic extract of B. concava was prepared from leaves and small branches. Qualitative phytochemical characterization indicated the presence of alkaloids, steroids, terpenoids, flavonoids, phenolic, and tannin compounds. The antimicrobial activity of this extract was assessed in a panel of microorganisms including Gram-positive bacteria, Gram-negative bacteria, and pathogenic yeasts. The extract displayed an important antimicrobial effect against Gram-positive bacteria, Candida albicans, and Cryptococcus neoformans but not against Gram-negatives, for which an intact Lipopolysaccharide is apparently the determinant of resistance to B. concava extracts. The hydroalcoholic extract was then fractionated through a Sephadex LH-20/methanol-ethyl acetate column. Afterward, the fractions were pooled according to a similar pattern visualized by TLC/UV analysis. Fractions obtained by this criterion were assessed for their antimicrobial activity against Staphylococcus aureus. The fraction presenting the most antimicrobial activity was HPLC-ESI-MS/MS, obtaining molecules related to caffeoylquinic acid, dicaffeoylquinic acid, and quercetin, among others. In conclusion, the extracts of B. concava showed strong antimicrobial activity, probably due to the presence of metabolites derived from phenolic acids, such as caffeoylquinic acid, and flavonoids, such as quercetin, which in turn could be responsible for helping with wound healing. In addition, the development of antimicrobial therapies based on the molecules found in B. concava could help to combat infection caused by pathogenic yeasts and Gram-positive bacteria, without affecting the Gram-negative microbiota.
Assuntos
Baccharis , Quercetina , Ácido Quínico/análogos & derivados , Chile , Espectrometria de Massas em Tandem , Compostos Fitoquímicos/farmacologia , Flavonoides/farmacologia , Extratos Vegetais/farmacologiaRESUMO
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.