Search Results (217)

The molecular mechanisms underlying the observed anticancer effects of flavonoids remain unclear. Increasing evidence shows that the aryl hydrocarbon receptor (AHR) plays a crucial role in neoplastic disease progression, establishing it as a potential drug target. This study evaluated the potential of hydroxy flavonoids, known for their anticancer properties, to interact with AHR, both in silico and in vitro, aiming to understand the mechanisms of action and identify selective AHR modulators. A PAS-B domain homology model was constructed to evaluate in silico interactions of chrysin, naringenin, quercetin apigenin and agathisflavone. The EROD activity assay measured the effects of flavonoids on AHR’s activity in human breast cancer cells (MCF7). Simulations showed that chrysin, apigenin, naringenin, and quercetin have the highest AHR binding affinity scores (−13.14 to −15.31), while agathisflavone showed low scores (−0.57 and −5.14). All tested flavonoids had the potential to inhibit AHR activity in a dose-dependent manner in the presence of an agonist (TCDD) in vitro. This study elucidates the distinct modulatory effects of flavonoids on AHR, emphasizing naringenin’s newly described antagonistic potential. It underscores the importance of understanding flavonoid’s molecular mechanisms, which is crucial for developing novel cancer therapies based on these molecules. Full article

The primary source of hard fiber globally is Agave sisalana Perrine, also known as sisal. In areas where sisal is grown, the roots of the plant are usually left in the field after it has stopped producing, which leads to soil degradation and decreased sisal productivity. It is, therefore, critical to find alternatives to reuse this waste. This study explores the potential use of sisal waste in the cosmetic industry by incorporating a hydroethanolic extract (HER) into a cream–gel formulation, taking advantage of the plant’s recognized ethnopharmacological value. The study involves analyzing the extract’s phytochemical composition (flavonoids) and evaluating its cytotoxicity. Subsequently, the antioxidant and antiglycation activities of the extract and cream–gel are evaluated, as well as ex vivo ocular toxicity, photoprotective activity, and preliminary stability analyses. The HER extract showed a flavonoid composition (catechin, kaempferol, isorhamnetin, and chrysin) and maintained cell viability above 70% throughout all time points analyzed in the MTT assay. Furthermore, the extract and the formulation demonstrated proven antioxidant and antiglycation activities. The cream–gel’s UVB and UVA protection effectiveness with the HER was comparable to that of synthetic UVB/UVA sunscreens, with the samples proving nonirritating and stable. In conclusion, the extract has a significant presence of flavonoids, and the cream–gel developed with it did not present cytotoxicity and met the stability requirements, indicating phytocosmetic potential with antioxidant, antiglycation, and photoprotective properties. Full article

The brain-derived neurotrophic factor (BDNF) plays a crucial role during neuronal development as well as during differentiation and synaptogenesis. They are important proteins present in the brain that support neuronal health and protect the neurons from detrimental signals. The results from the present study suggest BDNF expression can be increase up to ~8-fold by treating the neuroblastoma cells SHSY-5Y with an herbal extract of Oroxylum indicum (50 μg/mL) and ~5.5-fold under lipopolysaccharides (LPS)-induced inflammation conditions. The Oroxylum indicum extract (Sabroxy) was standardized to 10% oroxylin A, 6% chrysin, and 15% baicalein. In addition, Sabroxy has shown to possess antioxidant activity that could decrease the damage caused by the exacerbation of radicals during neurodegeneration. A mode of action of over expression of BDNF with and without inflammation is proposed for the Oroxylum indicum extract, where the three major hydroxyflavones exert their effects through additive or synergistic effects via five possible targets including GABA, Adenoside A2A and estrogen receptor bindings, anti-inflammatory effects, and reduced mitochondrial ROS production. Full article

The main goal of this study was to assess the bioactive and polysaccharide compositions, along with the antioxidant and antibacterial potentials, of five seaweeds collected from the northeastern coast of Algeria. Through Fourier transform infrared spectroscopy analysis and X-ray fluorescence spectroscopy, the study investigated the elemental composition of these seaweeds and their chemical structure. In addition, this study compared and identified the biochemical makeup of the collected seaweed by using cutting-edge methods like tandem mass spectrometry and ultra-high-performance liquid chromatography, and it searched for new sources of nutritionally valuable compounds. According to the study’s findings, Sargassum muticum contains the highest levels of extractable bioactive compounds, showing a phenolic compound content of 235.67 ± 1.13 µg GAE·mg⁻¹ and a total sugar content of 46.43 ± 0.12% DW. Both S. muticum and Dictyota dichotoma have high concentrations of good polyphenols, such as vanillin and chrysin. Another characteristic that sets brown algae apart is their composition. It showed that Cladophora laetevirens has an extracted bioactive compound content of 12.07% and a high capacity to scavenge ABTS⁺ radicals with a value of 78.65 ± 0.96 µg·mL⁻¹, indicating high antioxidant activity. In terms of antibacterial activity, S. muticum seaweed showed excellent growth inhibition. In conclusion, all five species of seaweed under investigation exhibited unique strengths, highlighting the variety of advantageous characteristics of these seaweeds, especially S. muticum. Full article

Chrysin is hypothesized to possess the ability to prevent different illnesses, such as diabetes, cancer, and neurodegenerative disorders. Nonetheless, chrysin has a low solubility under physiological conditions, resulting in limited bioavailability. In a previous study, we utilized an oil-in-water emulsion system (chrysin-ES or chrysin-NE) to encapsulate chrysin, thereby increasing its bioaccessibility and preserving its antioxidant and anti-Alzheimer’s properties. To promote the chrysin-ES as a supplementary and functional food, it was obligatory to carry out a safety assessment. Cytotoxicity testing showed that chrysin-ES was harmless, with no killing effect on 3T3-L1 (adipocytes), RAW 264.7 (macrophages), HEK293 (kidney cells), and LX-2 (hepatic stellate cells). The acute toxicity evaluation demonstrated that the 50% lethal dose (LD₅₀) for chrysin-ES was greater than 2000 mg/kg BW. Genotoxicity assessments found that chrysin-ES did not induce DNA mutations in vitro or in vivo. Furthermore, chrysin and chrysin-ES exhibited anti-mutagenic properties against PhIP-induced and IQ-induced mutagenesis in the Ames test, while they inhibited urethane-, ethyl methanesulfonate-, mitomycin C-, and N-nitrosomethylurea-mediated mutations in Drosophila. The present study illustrates the safety and anti-genotoxicity properties of chrysin-ES, allowing for the further development of chrysin-based food supplements and nutraceuticals. Full article

The search results offer comprehensive insights into the phenolic compounds, antioxidant, anti-inflammatory, cytotoxic effects, LC-MS/MS analysis, molecular docking, and MD simulation of the identified phenolic compounds in the Astragalus arpilobus subsp. hauarensis extract (AAH). The analysis revealed substantial levels of total phenolic content (TPC), with a measured value of 191 ± 0.03 mg GAE/g DM. This high TPC was primarily attributed to two key phenolic compounds: total flavonoid content (TFC) and total tannin content (TTC), quantified at 80.82 ± 0.02 mg QE/g DM and 51.91 ± 0.01 mg CE/g DM, respectively. LC-MS/MS analysis identified 28 phenolic compounds, with gallic acid, protocatechuic acid, catechin, and others. In the DPPH scavenging assay, the IC₅₀ value for the extract was determined to be 19.44 ± 0.04 μg/mL, comparable to standard antioxidants like BHA, BHT, ascorbic acid, and α-tocopherol. Regarding anti-inflammatory activity, the extract demonstrated a notably lower IC₅₀ value compared to both diclofenac and ketoprofen, with values of 35.73 µg/mL, 63.78 µg/mL, and 164.79 µg/mL, respectively. Cytotoxicity analysis revealed significant cytotoxicity of the A. arpilobus extract, with an LC₅₀ value of 28.84 µg/mL, which exceeded that of potassium dichromate (15.73 µg/mL), indicating its potential as a safer alternative for various applications. Molecular docking studies have highlighted chrysin as a promising COX-2 inhibitor, with favorable binding energies and interactions. Molecular dynamic simulations further support chrysin’s potential, showing stable interactions with COX-2, comparable to the reference ligand S58. Overall, the study underscores the pharmacological potential of A. arpilobus extract, particularly chrysin, as a source of bioactive compounds with antioxidant and anti-inflammatory properties. Further research is warranted to elucidate the therapeutic mechanisms and clinical implications of these natural compounds. Full article

Prostate cancer is frequently diagnosed and the leading cause of death in men worldwide. Prostate-specific antigen (PSA) blood tests and biopsies are the primary methods for diagnosing prostate cancer; however, their accuracy is less than 50%. Therefore, there is a need to develop diagnostic tests that minimize patient discomfort during examination and adequate biomarkers that are more accurate, sensitive, and specific for the detection of prostate cancer. This study investigated the application of metabolomics to identify biomarkers in prostate cancer biofluids. In addition, changes in prostate cancer metabolite levels induced by chrysin, a natural anticancer compound, were evaluated and compared with those in non-treated prostate cancer cells. Gas chromatography-mass spectrometry (GC-MS)-based metabolomic profiling was performed to investigate the differences in metabolic alterations among prostate cancer, normal prostate, and chrysin-treated prostate cancer cells. Pairwise comparisons of the extracellular fluid metabolomes were performed using principal component analysis (PCA), partial least squares–discriminant analysis (PLS-DA), and Student’s t-test. The results revealed significantly different patterns among the metabolite groups, including alcohols, amino acids, carboxylic acids, organic acids, sugars, and urea. The RWPE-1- and chrysin-treated PC-3 (PC-3 Chr) cell groups showed similar tendencies for 23 metabolites, while the groups showed significant differences from the PC-3 group. Most amino acids showed higher concentrations in PC-3 cells than in the normal cell line RWPE-1 cells and PC-3 Chr cells. Our results revealed that GC-MS might be an effective diagnostic tool to detect prostate cancer and contribute to finding new tumor markers for prostate cancer as the basis for new ideas. Full article

The present study focuses on the chemical characterization of a dry extract obtained from the species Ajuga chamaepitys (L.) Schreb, evaluating its antioxidant properties, toxicity, and in silico profile. Quantitative analysis of the dry extract revealed a notable amount of phytochemical compounds: 59.932 ± 21.167 mg rutin equivalents (mg REs)/g dry weight, 45.864 ± 4.434 mg chlorogenic acid equivalents (mg ChAEs)/g dry weight and, respectively, 83.307 ± 3.989 mg tannic acid equivalents (TAEs)/g dry weight. By UHPLC-HRMS/MS, the following were quantified as major compounds: caffeic acid (3253.8 μg/g extract) and kaempherol (3041.5 μg/g extract); more than 11 types of polyphenolic compounds were quantified (genistin 730.2 μg/g extract, naringenin 395 μg/g extract, apigenin 325.7 μg/g extract, galangin 283.3 μg/g extract, ferulic acid 254.3 μg/g extract, p-coumaric acid 198.2 μg/g extract, rutin 110.6 μg/g extract, chrysin 90.22 μg/g extract, syringic acid 84.2 μg/g extract, pinocembrin 32.7 μg/g extract, ellagic acid 18.2 μg/g extract). The antioxidant activity was in accordance with the amount of phytochemical compounds: IC₅₀DPPH = 483.6 ± 41.4 µg/mL, IC₅₀ABTS^•+ = 127.4 ± 20.2 µg/mL, and EC₅₀FRAP = 491.6 ± 2 µg/mL. On the larvae of Artemia sp., it was found that the extract has a low cytotoxic action. In silico studies have highlighted the possibility of inhibiting the activity of protein kinases CDK5 and GSK-3b for apigenin, galangin, and kaempferol, with possible utility for treating neurodegenerative pathologies and neuropathic pain. Further studies are warranted to confirm the predicted molecular mechanisms of action and to further investigate the therapeutic potential in animal models of neurological disorders. Full article

The natural flavonoid compound chrysin has promising anti-tumor effects. In this study, we aimed to investigate the mechanism by which chrysin inhibits the growth of non-small cell lung cancer (NSCLC). Through in vitro cell culture and animal models, we explored the impact of chrysin on the growth of NSCLC cells and the pro-cancer effects of tumor-associated macrophages (TAMs) and their mechanisms. We observed that M2-TAMs significantly promoted the growth and migration of NSCLC cells, while also markedly activating the autophagy level of these cells. Chrysin displayed a significant inhibitory effect on the growth of NSCLC cells, and it could also suppress the pro-cancer effects of M2-TAMs and inhibit their mediated autophagy. Furthermore, combining network pharmacology, we found that chrysin inhibited TAMs-mediated autophagy activation in NSCLC cells through the regulation of the CDK1/ULK1 signaling pathway, rather than the classical mTOR/ULK1 signaling pathway. Our study reveals a novel mechanism by which chrysin inhibits TAMs-mediated autophagy activation in NSCLC cells through the regulation of the CDK1/ULK1 pathway, thereby suppressing NSCLC growth. This discovery not only provides new therapeutic strategies for NSCLC but also opens up new avenues for further research on chrysin. Full article

In this study, the phytochemical composition, in vitro antioxidant, and anti-inflammatory effects of the aqueous and 60% ethanolic (EtOH) extracts of Santolina rosmarinifolia leaf, flower, and root were examined. The antioxidant activity of S. rosmarinifolia extracts was determined by 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays. The total phenolic content (TPC) of the extracts was measured by the Folin–Ciocalteu assay. The anti-inflammatory effect of the extracts was monitored by the Griess assay. The chemical composition of S. rosmarinifolia extracts was analysed using the LC-MS technique. According to our findings, 60% EtOH leaf extracts showed the highest Trolox equivalent antioxidant capacity (TEAC) values in both ABTS (8.39 ± 0.43 µM) and DPPH (6.71 ± 0.03 µM) antioxidant activity assays. The TPC values of the samples were in good correspondence with the antioxidant activity measurements and showed the highest gallic acid equivalent value (130.17 ± 0.01 µg/mL) in 60% EtOH leaf extracts. In addition, the 60% EtOH extracts of the leaves were revealed to possess the highest anti-inflammatory effect. The LC-MS analysis of S. rosmarinifolia extracts proved the presence of ascorbic acid, catalpol, chrysin, epigallocatechin, geraniol, isoquercitrin, and theanine, among others, for the first time. However, additional studies are needed to investigate the direct relationship between the chemical composition and physiological effects of the herb. The 60% EtOH extracts of S. rosmarinifolia leaves are potential new sources of natural antioxidants and anti-inflammatory molecules in the production of novel nutraceutical products. Full article

Flavonoids, a diverse group of polyphenolic compounds found abundantly in fruits, vegetables, and beverages like tea and wine, offer a plethora of health benefits. However, they have a potential interaction with drug metabolism, particularly through the inhibition of the cytochrome P450 3A4 enzyme, the most versatile and abundant enzyme in the liver. CYP3A4 is responsible for metabolizing approximately 50% of clinically prescribed drugs across diverse therapeutic classes, so these interactions have raised concerns about potential adverse effects. This review delves into the scientific evidence surrounding flavonoid-mediated CYP3A4 inhibition, exploring the inhibitory potential of investigated flavonoids and future implications. Kusehnol I, chrysin, leachianone A, and sophoraflavone G showed the largest inhibitory potentials and lowest IC₅₀ values. While the clinical significance of flavonoid-mediated CYP3A4 inhibition in dietary contexts is generally considered low due to moderate intake and complex interactions, it poses a potential concern for individuals consuming high doses of flavonoid supplements or concurrently taking medications metabolized by CYP3A4. This can lead to increased drug exposure, potentially triggering adverse reactions or reduced efficacy. Full article

Sepsis, a leading cause of death worldwide, is a harmful inflammatory condition that is primarily caused by an endotoxin released by Gram-negative bacteria. Effective targeted therapeutic strategies for sepsis are lacking. In this study, using an in vitro and in vivo mouse model, we demonstrated that CM1, a derivative of the natural polyphenol chrysin, exerts an anti-inflammatory effect by inducing the expression of the ubiquitin-editing protein TNFAIP3 and the NAD-dependent deacetylase sirtuin 1 (SIRT1). Interestingly, CM1 attenuated the Toll-like receptor 4 (TLR4)-induced production of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signalling pathways. In addition, CM1 induced the expression of TNFAIP3 and SIRT1 on TLR4-stimulated primary macrophages; however, the anti-inflammatory effect of CM1 was abolished by the siRNA-mediated silencing of TNFAPI3 or by the genetic or pharmacologic inhibition of SIRT1. Importantly, intravenous administration of CM1 resulted in decreased susceptibility to endotoxin-induced sepsis, thereby attenuating the production of pro-inflammatory cytokines and neutrophil infiltration into the lung compared to control mice. Collectively, these findings demonstrate that CM1 has therapeutic potential for diverse inflammatory diseases, including sepsis. Full article

Enhancing nanoparticles’ anti-cancer capabilities as drug carriers requires the careful adjustment of formulation parameters, including loading efficiency, drug/carrier ratio, and synthesis method. Small adjustments to these parameters can significantly influence the drug-loading efficiency of nanoparticles. Our study explored how chitosan and polyethylene glycol (PEG) coatings affect the structural properties, drug-loading efficiency, and anti-cancer efficacy of Fe₃O₄ nanoparticles (NPs). The loading efficiency of the NPs was determined using FTIR spectrometry and XRD. The quantity of chrysin incorporated into the coated NPs was examined using UV–Vis spectrometry. The effect of the NPs on cell viability and apoptosis was determined by employing the HCT 116 human colon carcinoma cell line. We showed that a two-fold increase in drug concentration did not impact the loading efficiency of Fe₃O₄ NPs coated with PEG. However, there was a 33 Å difference in the crystallite sizes obtained from chitosan-coated Fe₃O₄ NPs and drug concentrations of 1:0.5 and 1:2, resulting in decreased system stability. In conclusion, PEG coating exhibited a higher loading efficiency of Fe₃O₄ NPs compared to chitosan, resulting in enhanced anti-tumor effects. Furthermore, variations in the loaded amount of chrysin did not impact the crystallinity of PEG-coated NPs, emphasizing the stability and regularity of the system. Full article

Background and objectives: The incidence of chronic inflammatory pathologies has incrementally increased in recent years, as in the case of inflammatory bowel disease (IBD), which is characterized by intestinal epithelial barrier disruption, increased inflammatory mediator production and excessive tissue injury. Changes in eating habits might have played a key role in this scenario. Therefore, the interest in specific diet development and in functional food formulation has been growing. Phytoextracts from several origins, from plants to waste, enriched in bioactive molecules, alone or combined, might be a resource for the obtainment of an efficient synergistic beneficial. Thus, the aim of this study consists of evaluating the protective effects of artichoke, fenugreek and caigua (AFC) phytoextract original blend. Methods: In order to mimic the intestinal barrier’s inflammatory environment, Caco-2 cells were cultured and polarized on a transwell system and then exposed to a pro-inflammatory cytokine cocktail (TNFα and IL-1β). Before being exposed to an inflammatory stimulus, cells were pre-treated with an AFC digested blend, according to the INFOGEST in vitro static digestion protocol. After digestion, the content of active substances within the blended extract (ACFB) was revealed by UHPLC–ESI–HRMS analysis. The AFC digested extract’s protective effect was evaluated by measuring the transepithelial resistance (TEER) as a marker of barrier integrity and analysing the nuclear factor kappa B (NF-κB) pathway. Results: The TEER values improved in cells which were pre-treated with the AFC blend, relative to inflamed cells, suggesting a regulation in tight junction protein expression and/or localization. The transcription factor p65NF-κB is activated by phosphorylation under cytokine exposure, with a 160% increase in its target COX-2. Moreover, a 40-fold increase in IL-8 release was observed. Interestingly, in cells pre-treated with the AFC blend, the activated p65NF-κB was halved, compared to inflamed cells only. Furthermore, a consequent reduction by about 50% for COX-2 and by 30% for IL-8 was observed. Discussion: Taken together, these results highlight the anti-inflammatory potential of the AFC blend, probably due to the presence of flavonoids such as luteolin, apigenin and chrysin. This experimental evidence suggests that an AFC blend could be a good ingredient for food functionalization if further used in nutritional strategies. Full article

Buds of poplar trees (Populus species) are often covered with sticky, usually polyphenol-rich, exudates. Moreover, accessible data showed that some Populus bud extracts may be excellent antibacterial agents, especially against Gram-positive bacteria. Due to the fragmentary nature of the data found, we conducted a systematic screening study. The antimicrobial activity of two extract types (semi-polar—ethanolic and polar—ethanolic-water (50/50; V/V)) from 27 bud samples of different poplar taxons were compared. Antimicrobial assays were performed against Gram-positive (five strains) and Gram-negative (six strains) bacteria as well as fungi (three strains) and covered the determination of minimal inhibitory, bactericidal, and fungicidal concentrations. The composition of extracts was later investigated by ultra-high-performance liquid chromatography coupled with ultraviolet detection (UHPLC-DAD) and with electrospray-quadrupole-time-of-flight tandem mass spectrometry (UHPLC-ESI-qTOF-MS). As a result, most of the extracts exhibited good (MIC ≤ 62.5 µg/mL) or moderate (62.5 < MIC ≤ 500 µg/mL) activity against Gram-positives and Helicobacter pylori, as well as fungi. The most active were ethanolic extracts from P. trichocarpa, P. trichocarpa clone ‘Robusta’, and P. tacamahaca × P. trichocarpa. The strongest activity was observed for P. tacamahaca × P. trichocarpa. Antibacterial activity was supposedly connected with the abundant presence of flavonoids (pinobanksin, pinobanksin 3-acetate, chrysin, pinocembrin, galangin, isosakuranetin dihydrochalcone, pinocembrin dihydrochalcone, and 2′,6′-dihydroxy-4′-methoxydihydrochalcone), hydroxycinnamic acids monoesters (p-methoxycinnamic acid cinnamyl ester, caffeic acid phenethylate and different isomers of prenyl esters), and some minor components (balsacones). Full article