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15 pages, 1264 KiB  
Article
Dynamic Change of Volatile Fatty Acid Derivatives (VFADs) and Their Related Genes Analysis during Innovative Black Tea Processing
by Zi-Wei Zhou, Qing-Yang Wu, Yang Wu, Ting-Ting Deng, Yu-Qing Li, Li-Qun Tang, Ji-Hang He and Yun Sun
Foods 2024, 13(19), 3108; https://doi.org/10.3390/foods13193108 (registering DOI) - 28 Sep 2024
Abstract
Abstract: Volatile fatty acid derivatives (VFADs) play a significant role in contributing to flowery–fruity flavor black tea. Innovative black tea is typically crafted from aroma-intensive tea cultivars, such as Jinmudan, using defined production methodologies. In this study, the during-processing tea leaves of innovative [...] Read more.
Abstract: Volatile fatty acid derivatives (VFADs) play a significant role in contributing to flowery–fruity flavor black tea. Innovative black tea is typically crafted from aroma-intensive tea cultivars, such as Jinmudan, using defined production methodologies. In this study, the during-processing tea leaves of innovative black tea were applied as materials, and we selected a total of 45 VFADs, comprising 11 derived aldehydes, nine derived alcohols, and 25 derived esters. Furthermore, the dynamic variations of these VFADs were uncovered. Transcriptome analysis was performed to identify genes involved in the LOX (lipoxygenase) pathway, resulting in the identification of 17 CsLOX genes, one hydrogen peroxide lyase (CsHPL) gene, 11 alcohol dehydrogenases (CsADH) genes, 11 genes as acyl CoA oxidase (CsACOX) genes, and three allene oxide synthase (CsAOS) genes. Additionally, the expression levels of these genes were measured, indicating that the processing treatments of innovative black tea, particularly turn-over and fermentation, had a stimulation effect on most genes. Finally, qRT-PCR verification and correlation analysis were conducted to explain the relationship between VFADs and candidate genes. This study aims to provide a reference for ‌illuminating the formation mechanisms of aroma compounds in innovative black tea, thereby inspiring the optimization of innovative processing techniques and enhancing the overall quality of black tea. Full article
(This article belongs to the Special Issue Flavor and Sensory Analysis as a Tool for Quality Control of Foods)
20 pages, 11315 KiB  
Article
A Multiomics Evaluation of the Countermeasure Influence of 4-Week Cranberry Beverage Supplementation on Exercise-Induced Changes in Innate Immunity
by David C. Nieman, Camila A. Sakaguchi, James C. Williams, Jongmin Woo, Ashraf M. Omar, Fayaj A. Mulani, Qibin Zhang, Wimal Pathmasiri, Blake R. Rushing, Susan McRitchie, Susan J. Sumner, Jackie Lawson and Kevin C. Lambirth
Nutrients 2024, 16(19), 3250; https://doi.org/10.3390/nu16193250 - 26 Sep 2024
Viewed by 345
Abstract
Objectives: This study examined the effect of a 4-week unsweetened cranberry beverage (CRAN) (317 mg polyphenols) versus placebo beverage (PLAC) ingestion (240 mL/day) on moderating exercise-induced changes in innate immunity. Methods: Participants included 25 male and female non-elite cyclists. A randomized, placebo-controlled, double-blind [...] Read more.
Objectives: This study examined the effect of a 4-week unsweetened cranberry beverage (CRAN) (317 mg polyphenols) versus placebo beverage (PLAC) ingestion (240 mL/day) on moderating exercise-induced changes in innate immunity. Methods: Participants included 25 male and female non-elite cyclists. A randomized, placebo-controlled, double-blind crossover design was used with two 4-week supplementation periods and a 2-week washout period. Supplementation periods were followed by an intensive 2.25 h cycling bout. Six blood samples were collected before and after supplementation (in an overnight fasted state) and at 0 h, 1.5 h, 3 h, and 24 h post-exercise. Stool and urine samples were collected pre- and post-supplementation. Outcome measures included serum creatine kinase, myoglobin, and cortisol, complete blood counts, plasma untargeted proteomics, plasma-targeted oxylipins, untargeted urine metabolomics, and stool microbiome composition via whole genome shotgun (WGS) sequencing. Results: Urine CRAN-linked metabolites increased significantly after supplementation, but no trial differences in alpha or beta microbiota diversity were found in the stool samples. The 2.25 h cycling bout caused significant increases in plasma arachidonic acid (ARA) and 53 oxylipins (FDR q-value < 0.05). The patterns of increase for ARA, four oxylipins generated from ARA-cytochrome P-450 (CYP) (5,6-, 8,9-, 11,12-, and 14,15-diHETrEs), two oxylipins from linoleic acid (LA) and CYP (9,10-DiHOME, 12,13-DiHOME), and two oxylipins generated from LA and lipoxygenase (LOX) (9-HODE, 13-HODE) were slightly but significantly higher for the CRAN versus PLAC trial (all interaction effects, p < 0.05). The untargeted proteomics analysis showed that two protein clusters differed significantly between the CRAN and PLAC trials, with CRAN-related elevations in proteins related to innate immune activation and reduced levels of proteins related to the regulation of the complement cascade, platelet activation, and binding and uptake of ligands by scavenger receptors. No trial differences were found for cortisol and muscle damage biomarkers. Conclusions: CRAN versus PLAC juice resulted in a significant increase in CRAN-related metabolites but no differences in the gut microbiome. CRAN supplementation was associated with a transient and modest but significant post-exercise elevation in selected oxylipins and proteins associated with the innate immune system. Full article
(This article belongs to the Special Issue Sports Nutrition: Current and Novel Insights)
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26 pages, 6598 KiB  
Article
Biogenic Synthesis of Silver Nanoparticles Mediated by Aronia melanocarpa and Their Biological Evaluation
by Andreia Corciovă, Cornelia Mircea, Adrian Fifere, Ioana-Andreea Turin-Moleavin, Irina Roşca, Irina Macovei, Bianca Ivănescu, Ana-Maria Vlase, Monica Hăncianu and Ana Flavia Burlec
Life 2024, 14(9), 1211; https://doi.org/10.3390/life14091211 - 23 Sep 2024
Viewed by 598
Abstract
In the present study, two A. melanocarpa berry extracts were used for the synthesis of silver nanoparticles (AgNPs). After the optimization of synthesis, the AgNPs were characterized using UV–Vis, FTIR, EDX, DLS, and STEM analyses. The stability in different media, phytotoxicity, as well [...] Read more.
In the present study, two A. melanocarpa berry extracts were used for the synthesis of silver nanoparticles (AgNPs). After the optimization of synthesis, the AgNPs were characterized using UV–Vis, FTIR, EDX, DLS, and STEM analyses. The stability in different media, phytotoxicity, as well as antimicrobial and antioxidant activities were also evaluated. The ideal synthesis conditions were represented by a 3 mM AgNO3 concentration, 1:9 extract:AgNO3 volume ratio, alkaline medium, and stirring at 40 °C for 120 min. The synthesis was confirmed by the surface plasmon resonance (SPR) peak at 403 nm, and the strong signal at 3 keV from the EDX spectra. FTIR analysis indicated that polyphenols, polysaccharides, and amino acids could be the compounds responsible for synthesis. Stability tests and the negative zeta potential values showed that phytocompounds also play a role in the stabilization and capping of AgNPs. The preliminary phytotoxicity studies on T. aestivum showed that both the extracts and their corresponding AgNPs had an impact on the growth of roots and shoots as well as on the microscopic structure of leaves. The synthesized AgNPs presented antimicrobial activity against S. aureus, E. coli, and C. albicans. Moreover, considering the results obtained in the lipoxygenase inhibition, the DPPH and hydroxyl scavenging activities, and the ferrous ion chelating assay, AgNPs exhibit promising antioxidant activity. Full article
(This article belongs to the Special Issue Implications of Bioactive Compounds in Lifelong Disorders)
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19 pages, 3489 KiB  
Article
Rhododendron luteum Sweet Flower Supercritical CO2 Extracts: Terpenes Composition, Pro-Inflammatory Enzymes Inhibition and Antioxidant Activity
by Lena Łyko, Marta Olech, Urszula Gawlik, Agnieszka Krajewska, Danuta Kalemba, Katarzyna Tyśkiewicz, Narcyz Piórecki, Andriy Prokopiv and Renata Nowak
Int. J. Mol. Sci. 2024, 25(18), 9952; https://doi.org/10.3390/ijms25189952 - 15 Sep 2024
Viewed by 610
Abstract
Terpenes are plant secondary metabolites known for their anti-inflammatory and antioxidant activities. According to ethnobotanical knowledge, Rhododendron luteum Sweet was used in traditional medicine against inflammation. The present study was conducted to determine the triterpene profile and antioxidant and anti-inflammatory activity of supercritical [...] Read more.
Terpenes are plant secondary metabolites known for their anti-inflammatory and antioxidant activities. According to ethnobotanical knowledge, Rhododendron luteum Sweet was used in traditional medicine against inflammation. The present study was conducted to determine the triterpene profile and antioxidant and anti-inflammatory activity of supercritical CO2 (SC-CO2) extracts of Rhododendron luteum Sweet flower (RLF). An LC-APCI-MS/MS analysis showed the presence of eight pentacyclic triterpenes and one phytosterol in the extracts obtained with pure CO2 as well as CO2 with the addition of aqueous ethanol as a co-solvent. Among the compounds detected, oleanolic/ursolic acid, β-sitosterol and 3β-taraxerol were the most abundant. The extract obtained with pure SC-CO2 was additionally subjected to HS-SPME-GC-FID-MS, which revealed more than 100 volatiles, mainly eugenol, β-phenylethanol, dodecane, β-caryophyllene, estragole and (Z)- and (E)-cinnamyl alcohol, followed by δ-cadinene. The extracts demonstrated significant hyaluronidase inhibition and exhibited varying modes of lipoxygenase and xanthine oxidase inhibitory activities. The studies of RLF have shown that their SC-CO2 extracts can be a rich source of triterpenes with anti-inflammatory potential. Full article
(This article belongs to the Special Issue Bioactive Compounds and Their Antioxidant Role)
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18 pages, 2181 KiB  
Review
Dysregulation of the Arachidonic Acid Pathway in Cystic Fibrosis: Implications for Chronic Inflammation and Disease Progression
by Simona D’Orazio and Domenico Mattoscio
Pharmaceuticals 2024, 17(9), 1185; https://doi.org/10.3390/ph17091185 - 9 Sep 2024
Viewed by 542
Abstract
Cystic fibrosis (CF) is the most common fatal genetic disease among Caucasian people, with over 2000 mutations in the CFTR gene. Although highly effective modulators have been developed to rescue the mutant CFTR protein, unresolved inflammation and persistent infections still threaten the lives [...] Read more.
Cystic fibrosis (CF) is the most common fatal genetic disease among Caucasian people, with over 2000 mutations in the CFTR gene. Although highly effective modulators have been developed to rescue the mutant CFTR protein, unresolved inflammation and persistent infections still threaten the lives of patients. While the central role of arachidonic acid (AA) and its metabolites in the inflammatory response is widely recognized, less is known about their impact on immunomodulation and metabolic implications in CF. To this end, here we provided a comprehensive analysis of the AA metabolism in CF. In this context, CFTR dysfunction appeared to complexly disrupt normal lipid processing, worsening the chronic airway inflammation, and compromising the immune responses to bacterial infections. As such, potential strategies targeting AA and its inflammatory mediators are being investigated as a promising approach to balance the inflammatory response while mitigating disease progression. Thus, a deeper understanding of the AA pathway dysfunction in CF may open innovative avenues for designing more effective therapeutic interventions. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Cystic Fibrosis)
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20 pages, 5656 KiB  
Article
Potential of Coffee Cherry Pulp Extract against Polycyclic Aromatic Hydrocarbons in Air Pollution Induced Inflammation and Oxidative Stress for Topical Applications
by Weeraya Preedalikit, Chuda Chittasupho, Pimporn Leelapornpisid, Natthachai Duangnin and Kanokwan Kiattisin
Int. J. Mol. Sci. 2024, 25(17), 9416; https://doi.org/10.3390/ijms25179416 - 30 Aug 2024
Viewed by 484
Abstract
Airborne particulate matter (PM) contains polycyclic aromatic hydrocarbons (PAHs) as primary toxic components, causing oxidative damage and being associated with various inflammatory skin pathologies such as premature aging, atopic dermatitis, and psoriasis. Coffee cherry pulp (CCS) extract, rich in chlorogenic acid, caffeine, and [...] Read more.
Airborne particulate matter (PM) contains polycyclic aromatic hydrocarbons (PAHs) as primary toxic components, causing oxidative damage and being associated with various inflammatory skin pathologies such as premature aging, atopic dermatitis, and psoriasis. Coffee cherry pulp (CCS) extract, rich in chlorogenic acid, caffeine, and theophylline, has demonstrated strong antioxidant properties. However, its specific anti-inflammatory effects and ability to protect macrophages against PAH-induced inflammation remain unexplored. Thus, this study aimed to evaluate the anti-inflammatory properties of CCS extract on RAW 264.7 macrophage cells exposed to atmospheric PAHs, compared to chlorogenic acid (CGA), caffeine (CAF), and theophylline (THP) standards. The CCS extract was assessed for its impact on the production of nitric oxide (NO) and expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Results showed that CCS extract exhibited significant antioxidant activities and effectively inhibited protease and lipoxygenase (LOX) activities. The PAH induced the increase in intracellular reactive oxygen species, NO, TNF-α, IL-6, iNOS, and COX-2, which were markedly suppressed by CCS extract in a dose-dependent manner, comparable to the effects of chlorogenic acid, caffeine, and theophylline. In conclusion, CCS extract inhibits PAH-induced inflammation by reducing pro-inflammatory cytokines and reactive oxygen species (ROS) production in RAW 264.7 cells. This effect is likely due to the synergistic effects of its bioactive compounds. Chlorogenic acid showed strong antioxidant and anti-inflammatory activities, while caffeine and theophylline enhanced anti-inflammatory activity. CCS extract did not irritate the hen’s egg chorioallantoic membrane. Therefore, CCS extract shows its potential as a promising cosmeceutical ingredient for safely alleviating inflammatory skin diseases caused by air pollution. Full article
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14 pages, 1440 KiB  
Article
An Investigation of Volatile Flavor Compounds and Lipolysis-Oxidation in Coppa as Affected by the Inoculation of Coagulase-Negative Staphylococcus during the Air-Drying Stage
by Jialing Ye, Xuying Zhang, Shuge Yuan, Yuemei Zhang, Jinxuan Cao, Wendi Teng and Ying Wang
Foods 2024, 13(17), 2723; https://doi.org/10.3390/foods13172723 - 28 Aug 2024
Viewed by 491
Abstract
This study aimed to explore the effects of coagulase-negative Staphylococcus inoculation on flavor generation and lipolysis-oxidation in Coppa. Acid lipase, neutral lipase, phospholipase, and lipoxygenase (LOX) activities, as well as free fatty acids, volatile compounds, and sensory evaluation, were determined during the fermentation [...] Read more.
This study aimed to explore the effects of coagulase-negative Staphylococcus inoculation on flavor generation and lipolysis-oxidation in Coppa. Acid lipase, neutral lipase, phospholipase, and lipoxygenase (LOX) activities, as well as free fatty acids, volatile compounds, and sensory evaluation, were determined during the fermentation and air-drying processes of Coppa over 40 days. Staphylococcus carnosus and Staphylococcus xylosus or a combination of both strains were selected for this study, and natural fermentation was treated as a control. The results showed that Staphylococcus inoculation significantly enhanced lipase and LOX activities, and mixed strains had a superior effect. Palmitic acid, stearic acid, linoleic acid, and oleic acid were identified as the predominant free fatty acids in Coppa, with the mixed fermentation group exhibiting the highest contents. Acids, aldehydes, alcohols, ketones, esters, and phenols were found for the volatile compounds in Coppa. These findings thus suggested a positive role of Staphylococcus inoculation in activating lipolysis-oxidation and contributing to the flavor formation of Coppa during the air-drying stage. Full article
(This article belongs to the Special Issue Flavor Formation and Quality Maintenance in Meat Processing)
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17 pages, 4875 KiB  
Article
Carbon Dots-Mediated Photodynamic Treatment Reduces Postharvest Senescence and Decay of Grapes by Regulating the Antioxidant System
by Zhi-Jing Ni, Ying Xue, Wei Wang, Juan Du, Kiran Thakur, Wen-Ping Ma and Zhao-Jun Wei
Foods 2024, 13(17), 2717; https://doi.org/10.3390/foods13172717 - 27 Aug 2024
Viewed by 451
Abstract
Grapes are susceptible to mold and decay during postharvest storage, and developing new technologies to extend their storage period has important application value. Photodynamic technology (PDT) in concurrence with carbon dots (CDs) proposes an innovative and eco-friendly preservation strategy. We examined the effects [...] Read more.
Grapes are susceptible to mold and decay during postharvest storage, and developing new technologies to extend their storage period has important application value. Photodynamic technology (PDT) in concurrence with carbon dots (CDs) proposes an innovative and eco-friendly preservation strategy. We examined the effects of carbon dots combined with photodynamic treatment on postharvest senescence and antioxidant system of table grape. The compounding of photodynamic technology with a 0.06 g L−1 CDs solution could possibly extend the postharvest storage period of grape berries. Through this strategy, we achieved a decreased rate of fruit rotting and weight loss alongside the delayed deterioration of fruit firmness, soluble solids, and titratable acid. As paired with photodynamic technology, CDs considerably decreased the postharvest storage loss of phenols, flavonoids, and reducing sugars as compared to the control group. Concurrently, it remarkably postponed the build-up of hydrogen peroxide (H2O2), superoxide anion (O2∙−), and malondialdehyde (MDA); elevated the levels of reduced ascorbic acid (AsA) and reduced glutathione (GSH); lowered the levels of dehydroascorbic acid (DHA) and oxidized glutathione (GSSG); raised the ratios of AsA/DHA and GSSH/GSSG; encouraged the activities of superoxide dismutase (SOD) and phenylalanine ammonia-lyase (PAL); and inhibited the activities of polyphenol oxidase (PPO) and lipoxygenase (LOX). Furthermore, it enhanced the iron reduction antioxidant capacity (FRAP) and DPPH radical scavenging capacity of grape berries. CDs combined with photodynamic treatment could efficiently lessen postharvest senescence and decay of grape berry while extending the storage time. Full article
(This article belongs to the Special Issue Postharvest Storage and Preservation of Fruits and Vegetables)
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20 pages, 6644 KiB  
Article
Monitoring Fruit Growth and Development in Apricot (Prunus armeniaca L.) through Gene Expression Analysis
by Germán Ortuño-Hernández, María Sánchez, David Ruiz, Pedro Martínez-Gómez and Juan Alfonso Salazar
Int. J. Mol. Sci. 2024, 25(16), 9081; https://doi.org/10.3390/ijms25169081 - 21 Aug 2024
Viewed by 476
Abstract
The main objective of this study was to monitor apricot development and ripening through gene expression analysis of key candidate genes using the RT-qPCR technique. Eight apricot cultivars were selected to analyze phenological and genetic patterns from pre-ripening stages through to postharvest. In [...] Read more.
The main objective of this study was to monitor apricot development and ripening through gene expression analysis of key candidate genes using the RT-qPCR technique. Eight apricot cultivars were selected to analyze phenological and genetic patterns from pre-ripening stages through to postharvest. In addition, 19 selected genes were analyzed in the contrasting cultivars ‘Cebas Red’ and ‘Rojo Pasión’ in different stages (two preharvest stages S1 and S2, one harvest stage S3, and two postharvest stages S4 and S5). This pool of genes included genes related to fruit growth and ripening, genes associated with fruit color, and genes linked to the fruit’s nutraceutical aspects. Among the studied genes, Polygalacturonase (PG), Pectin methylesterase (PME), Aminocyclopropane-1-carboxylate synthase (ACS), and Myo-inositol-1-phosphate synthase (INO1) were directly related to fruit maturation and quality. Significant differential expression was observed between the cultivars, which correlated with variations in firmness, shelf life, and sensory characteristics of the apricots. ‘Rojo Pasión’ displayed high levels of PG, associated with rapid maturation and shorter postharvest shelf life, whereas ‘Cebas Red’ exhibited lower levels of this gene, resulting in greater firmness and extended shelf life. Genes CCD4, CRTZ, and ZDS, related to carotenoids, showed varied expression patterns during growth and postharvest stages, with higher levels in ‘Rojo Pasión’. On the other hand, Sucrose synthase (SUSY) and Lipoxygenase (LOX2) were prominent during the postharvest and growth stages, respectively. Additionally, GDP-L-galactose phosphorylase (VTC2_5) was linked to better postharvest performance. This research provides valuable insights for future breeding initiatives aimed at enhancing the quality and sustainability of apricot cultivation. Full article
(This article belongs to the Special Issue Advances in Research on Fruit Crop Breeding and Genetics: 3rd Edition)
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15 pages, 13437 KiB  
Article
Integrative Analysis of Transcriptomic Profiles and Physiological Responses Provide New Insights into Drought Stress Tolerance in Oil Palm (Elaeis guineensis Jacq.)
by Fernan Santiago Mejía-Alvarado, Arley Fernando Caicedo-Zambrano, David Botero-Rozo, Leonardo Araque, Cristihian Jarri Bayona-Rodríguez, Seyed Mehdi Jazayeri, Carmenza Montoya, Iván Ayala-Díaz, Rodrigo Ruiz-Romero and Hernán Mauricio Romero
Int. J. Mol. Sci. 2024, 25(16), 8761; https://doi.org/10.3390/ijms25168761 - 12 Aug 2024
Viewed by 734
Abstract
Oil palm (Elaeis guineensis Jacq.) is a highly productive crop economically significant for food, cosmetics, and biofuels. Abiotic stresses such as low water availability, salt accumulation, and high temperatures severely impact oil palm growth, physiology, and yield by restricting water flux among [...] Read more.
Oil palm (Elaeis guineensis Jacq.) is a highly productive crop economically significant for food, cosmetics, and biofuels. Abiotic stresses such as low water availability, salt accumulation, and high temperatures severely impact oil palm growth, physiology, and yield by restricting water flux among soil, plants, and the environment. While drought stress’s physiological and biochemical effects on oil palm have been extensively studied, the molecular mechanisms underlying drought stress tolerance remain unclear. Under water deficit conditions, this study investigates two commercial E. guineensis cultivars, IRHO 7001 and IRHO 2501. Water deficit adversely affected the physiology of both cultivars, with IRHO 2501 being more severely impacted. After several days of water deficit, there was a 40% reduction in photosynthetic rate (A) for IRHO 7001 and a 58% decrease in IRHO 2501. Further into the drought conditions, there was a 75% reduction in A for IRHO 7001 and a 91% drop in IRHO 2501. Both cultivars reacted to the drought stress conditions by closing stomata and reducing the transpiration rate. Despite these differences, no significant variations were observed between the cultivars in stomatal conductance, transpiration, or instantaneous leaf-level water use efficiency. This indicates that IRHO 7001 is more tolerant to drought stress than IRHO 2501. A differential gene expression and network analysis was conducted to elucidate the differential responses of the cultivars. The DESeq2 algorithm identified 502 differentially expressed genes (DEGs). The gene coexpression network for IRHO 7001 comprised 274 DEGs and 46 predicted HUB genes, whereas IRHO 2501’s network included 249 DEGs and 3 HUB genes. RT-qPCR validation of 15 DEGs confirmed the RNA-Seq data. The transcriptomic profiles and gene coexpression network analysis revealed a set of DEGs and HUB genes associated with regulatory and transcriptional functions. Notably, the zinc finger protein ZAT11 and linoleate 13S-lipoxygenase 2-1 (LOX2.1) were overexpressed in IRHO 2501 but under-expressed in IRHO 7001. Additionally, phytohormone crosstalk was identified as a central component in the response and adaptation of oil palm to drought stress. Full article
(This article belongs to the Special Issue Recent Research in Plant Abiotic Stress)
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18 pages, 1425 KiB  
Article
Trolox, Ferulic, Sinapic, and Cinnamic Acid Derivatives of Proline and GABA with Antioxidant and/or Anti-Inflammatory Properties
by Georgios Papagiouvannis, Panagiotis Theodosis-Nobelos and Eleni A. Rekka
Molecules 2024, 29(16), 3763; https://doi.org/10.3390/molecules29163763 - 8 Aug 2024
Viewed by 640
Abstract
Degenerative conditions, such as neurodegenerative disorders (Alzheimer’s disease (AD), Parkinson’s disease (PD)) and cardiovascular diseases, are complex, multifactorial disorders whose pathophysiology has not been fully elucidated yet. As a result, the available treatment options cannot eliminate these diseases radically, but only alleviate the [...] Read more.
Degenerative conditions, such as neurodegenerative disorders (Alzheimer’s disease (AD), Parkinson’s disease (PD)) and cardiovascular diseases, are complex, multifactorial disorders whose pathophysiology has not been fully elucidated yet. As a result, the available treatment options cannot eliminate these diseases radically, but only alleviate the symptoms. Both inflammatory processes and oxidation are key factors in the development and evolution of neurodegeneration, while acetylcholinesterase inhibitors are the most used therapeutic options against AD. In this work, following the multi-targeting compound approach, we designed and synthesized a series of proline and gamma-aminobutyric acid (GABA) amides with various acidic moieties that possess an antioxidant and/or anti-inflammatory potency. Proline is the pharmacophore of nootropic drugs (e.g., piracetam) used for memory improvement, while GABA is the main inhibitory neurotransmitter in the central nervous system. The designed molecules were subjected to a preliminary screening of their bioactivity in antioxidant and anti-inflammatory assays, as well as against acetylcholinesterase. Most of the synthesized compounds could inhibit lipid peroxidation (IC50 as low as 8 μΜ) and oxidative protein glycation (inhibition of up to 48%) and reduce the 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH). In addition, all of the compounds were moderate inhibitors of lipoxygenase (LOX) (up to 46% at 100 μΜ) and could decrease carrageenan-induced paw edema in rats by up to 55%. Finally, some of the compounds were moderate acetylcholinesterase inhibitors (IC50 as low as 219 μΜ). The results confirmed the design rationale, indicating that the compounds could be further optimized as multi-targeting molecules directed against degenerative conditions. Full article
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16 pages, 1285 KiB  
Article
Differential Oxidative Stress Management in Industrial Hemp (IH: Cannabis sativa L.) for Fiber under Saline Regimes
by Naveen Dixit
Metabolites 2024, 14(8), 420; https://doi.org/10.3390/metabo14080420 - 31 Jul 2024
Viewed by 657
Abstract
In the current study, two commercial industrial hemp (IH) fiber varieties (V1: CFX-2 and V2: Henola) were assessed for their ability to regulate salt-induced oxidative stress metabolism. For 30 days, plants were cultivated in greenhouse environments with five different salinity treatments (0, 50, [...] Read more.
In the current study, two commercial industrial hemp (IH) fiber varieties (V1: CFX-2 and V2: Henola) were assessed for their ability to regulate salt-induced oxidative stress metabolism. For 30 days, plants were cultivated in greenhouse environments with five different salinity treatments (0, 50, 80, 100, 150, and 200 mM NaCl). Hydrogen peroxide (H2O2), malondialdehyde (MDA), and lipoxygenase (LOX) and antioxidant enzymes (superoxide dismutase (SOD), catalase, guaiacol peroxidase (GPOD), ascorbate peroxidase (APX), glutathione reductase (GR), and glutathione-S-transferase (GST)) were assessed in fully expanded leaves. At 200 and 100 mM NaCl concentrations, respectively, 30 days after saline treatment, plants in V1 and V2 did not survive. At 80 mM NaCl, the leaves of V2 showed higher concentrations of H2O2, MDA, and LOX than those of V1. Higher SOD, CAT, GPOD, APX, GR, and GST activity in the leaves of V1 up to 100 mM NaCl resulted in lower levels of H2O2 and MDA. At 80 mM NaCl, V2 demonstrated the total failure of the antioxidant defense mechanism. These results reveal that V1 demonstrated stronger salt tolerance than V2, in part due to better antioxidant metabolism. Full article
(This article belongs to the Special Issue Effects of Biotic/Abiotic Stress on Plant Metabolism)
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12 pages, 1803 KiB  
Brief Report
Anti-Inflammatory Potential of Pygeum africanum Bark Extract: An In Vitro Study of Cytokine Release by Lipopolysaccharide-Stimulated Human Peripheral Blood Mononuclear Cells
by Agustín Villar, Fredy Silva-Fuentes, Anna Mulà and Andrea Zangara
Int. J. Mol. Sci. 2024, 25(15), 8298; https://doi.org/10.3390/ijms25158298 - 30 Jul 2024
Viewed by 1808
Abstract
Pygeum africanum bark has been shown to inhibit the production of pro-inflammatory prostaglandins in the prostate and reduces the production of leukotrienes and other 5-lipoxygenase (5-LO) metabolites. It has been suggested that inflammation plays an important role in the pathophysiology of benign prostatic [...] Read more.
Pygeum africanum bark has been shown to inhibit the production of pro-inflammatory prostaglandins in the prostate and reduces the production of leukotrienes and other 5-lipoxygenase (5-LO) metabolites. It has been suggested that inflammation plays an important role in the pathophysiology of benign prostatic hyperplasia (BPH). Data from clinical trials have shown that P. africanum improves the symptoms and objective measures of BPH. This in vitro study aimed to assess the anti-inflammatory potential of a proprietary Pygeum bark standardized extract (Prunera®) on cytokine release from lipopolysaccharide-stimulated human peripheral blood mononuclear cells (PBMCs). PBMCs were obtained from four donors, and a bead-based assay (ProcartaPlex™ panel) was used for the detection and quantitation of cytokines. Pygeum africanum bark standardized extract (PABE) induced a statistically significant decrease (p < 0.05) of IL-6 in three donors. Other effects were as follows: IL-2 was lowered in all donors in the absence of a clear dose–response relationship; IL-4, IL-5, IL-9, and IL-13 levels were decreased in most donors; IL-22 levels seemed to be suppressed only for donor 4 at lower and medium concentrations; and IL-27 and TNF-α levels decreased at all PABE concentrations in all donors. The anti-inflammatory effect of PABE, particularly the reduction in IL-6 as a marker of inflammation, supports the potential use of this natural compound in the management of BPH and other conditions in which pro-inflammatory cytokines are involved in their underlying pathophysiological mechanisms. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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20 pages, 7443 KiB  
Article
Interactions between Inhibitors and 5-Lipoxygenase: Insights from Gaussian Accelerated Molecular Dynamics and Markov State Models
by Yuyang Liu, Kaiyu Wang, Fuyan Cao, Nan Gao and Wannan Li
Int. J. Mol. Sci. 2024, 25(15), 8295; https://doi.org/10.3390/ijms25158295 - 30 Jul 2024
Viewed by 596
Abstract
Inflammation is a protective stress response triggered by external stimuli, with 5-lipoxygenase (5LOX) playing a pivotal role as a potent mediator of the leukotriene (Lts) inflammatory pathway. Nordihydroguaiaretic acid (NDGA) functions as a natural orthosteric inhibitor of 5LOX, while 3-acetyl-11-keto-β-boswellic acid (AKBA) acts [...] Read more.
Inflammation is a protective stress response triggered by external stimuli, with 5-lipoxygenase (5LOX) playing a pivotal role as a potent mediator of the leukotriene (Lts) inflammatory pathway. Nordihydroguaiaretic acid (NDGA) functions as a natural orthosteric inhibitor of 5LOX, while 3-acetyl-11-keto-β-boswellic acid (AKBA) acts as a natural allosteric inhibitor targeting 5LOX. However, the precise mechanisms of inhibition have remained unclear. In this study, Gaussian accelerated molecular dynamics (GaMD) simulation was employed to elucidate the inhibitory mechanisms of NDGA and AKBA on 5LOX. It was found that the orthosteric inhibitor NDGA was tightly bound in the protein’s active pocket, occupying the active site and inhibiting the catalytic activity of the 5LOX enzyme through competitive inhibition. The binding of the allosteric inhibitor AKBA induced significant changes at the distal active site, leading to a conformational shift of residues 168–173 from a loop to an α-helix and significant negative correlated motions between residues 285–290 and 375–400, reducing the distance between these segments. In the simulation, the volume of the active cavity in the stable conformation of the protein was reduced, hindering the substrate’s entry into the active cavity and, thereby, inhibiting protein activity through allosteric effects. Ultimately, Markov state models (MSM) were used to identify and classify the metastable states of proteins, revealing the transition times between different conformational states. In summary, this study provides theoretical insights into the inhibition mechanisms of 5LOX by AKBA and NDGA, offering new perspectives for the development of novel inhibitors specifically targeting 5LOX, with potential implications for anti-inflammatory drug development. Full article
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17 pages, 753 KiB  
Article
German Chamomile (Matricaria chamomilla L.) Flower Extract, Its Amino Acid Preparations and 3D-Printed Dosage Forms: Phytochemical, Pharmacological, Technological, and Molecular Docking Study
by Oleh Koshovyi, Janne Sepp, Valdas Jakštas, Vaidotas Žvikas, Igor Kireyev, Yevhen Karpun, Vira Odyntsova, Jyrki Heinämäki and Ain Raal
Int. J. Mol. Sci. 2024, 25(15), 8292; https://doi.org/10.3390/ijms25158292 - 29 Jul 2024
Viewed by 698
Abstract
German chamomile (Matricaria chamomilla L.) is an essential oil- containing medicinal plant used worldwide. The aim of this study was to gain knowledge of the phytochemical composition and the analgesic and soporific activity of Matricaria chamomilla L. (German chamomile) flower extract and [...] Read more.
German chamomile (Matricaria chamomilla L.) is an essential oil- containing medicinal plant used worldwide. The aim of this study was to gain knowledge of the phytochemical composition and the analgesic and soporific activity of Matricaria chamomilla L. (German chamomile) flower extract and its amino acid preparations, to predict the mechanisms of their effects by molecular docking and to develop aqueous printing gels and novel 3D-printed oral dosage forms for the flower extracts. In total, 22 polyphenolic compounds and 14 amino acids were identified and quantified in the M. chamomilla extracts. In vivo animal studies with rodents showed that the oral administration of such extracts revealed the potential for treating of sleep disorders and diseases accompanied by pain. Amino acids were found to potentiate these effects. Glycine enhanced the analgesic activity the most, while lysine and β-alanine improved the soporific activity. The molecular docking analysis revealed a high probability of γ-aminobutyric acid type A (GABAA) and N-methyl-D-aspartate (NMDA) receptor antagonism and 5-lipoxygenase (LOX-5) inhibition by the extracts. A polyethylene oxide (PEO)-based gel composition with the M. chamomilla extracts was proposed for preparing a novel 3D-printed dosage form for oral administration. These 3D-printed extract preparations can be used, for example, in dietary supplement applications. Full article
(This article belongs to the Special Issue New Research on Bioactive Natural Products)
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