Search Results (307)

Isoquercitrin, a monoglucoside form of quercetin, exhibits superior antioxidant, anti-inflammatory, and cardiovascular protective effects in comparison to its precursor, rutin. However, its natural abundance is limited. This study aimed to increase the functional value of Diospyros lotus leaf extract through enzymatic conversion of rutin to isoquercitrin using α-l-rhamnosidase and to evaluate the changes in biological activities after conversion. A sugar-free D. lotus leaf extract was prepared and subjected to enzymatic hydrolysis with α-l-rhamnosidase under optimized conditions (pH 5.5, 55 °C, and 0.6 U/mL). Isoquercitrin production was monitored via high-performance liquid chromatography. Antioxidant and anti-inflammatory activities were assessed using the 2,2-diphenyl-1-picrylhydrazyl radical scavenging and lipoxygenase (LOX) inhibition assays, respectively. The enzymatic reaction resulted in complete conversion of 30 mM rutin into isoquercitrin within 180 min, increasing isoquercitrin content from 9.8 to 39.8 mM. The enzyme-converted extract exhibited significantly enhanced antioxidant activity, with a 48% improvement in IC₅₀ value compared with the untreated extract. Similarly, LOX inhibition increased from 39.2% to 48.3% after enzymatic conversion. Both extracts showed higher inhibition than isoquercitrin alone, indicating synergistic effects of other phytochemicals present in the extract. This study is the first to demonstrate that α-l-rhamnosidase-mediated conversion of rutin to isoquercitrin in D. lotus leaf extract significantly improves its antioxidant and anti-inflammatory activities. The enzymatically enhanced extract shows potential as a functional food or therapeutic ingredient. Full article

The cigarette production from Nicotiana tabacum generates significant amounts of waste, with an estimated 68.31 million tons of pre- and post-harvest waste discarded annually. The pre-harvest waste includes the upper parts of the plant, inflorescences, and bracts, which are removed to help the growth of the lower leaves. This study explores the potential of apical leaves from Nicotiana tabacum var. Virginia, discarded during the budding stage (pre-harvest waste). The leaves were extracted using environmentally friendly solvents (green solvents), including distilled water (DW) and two natural deep eutectic solvents (NaDESs), one consisting of simple sugars, fructose, glucose, and sucrose (FGS) and the other consisting of choline chloride and urea (CU). The anti-inflammatory and anti-aging potential of these green extracts was assessed by the inhibition of key enzymes related to skin aging. The xanthine oxidase and lipoxygenase activities were mostly inhibited by CU extracts with IC₅₀ values of 63.50 and 8.0 μg GAE/mL, respectively. The FGS extract exhibited the greatest hyaluronidase inhibition (49.20%), followed by the CU extract (33.20%) and the DW extract (20.80%). Regarding elastase and collagenase inhibition, the CU extract exhibited the highest elastase inhibition, while all extracts inhibited collagenase activity, with values exceeding 65%. Each extract had a distinct chemical profile determined by LC-ESI-QTOF-MS/MS and spectrophotometric methods, with several shared compounds present in different proportions. CU extract is characterized by high concentrations of rutin, nicotiflorin, and azelaic acid, while FGS and DW extracts share major compounds such as quinic acid, fructosyl pyroglutamate, malic acid, and gluconic acid. Ames test and Caenorhabditis elegans assay demonstrated that at the concentrations at which the green tobacco extracts exhibit biological activities, they did not show toxicity. The results support the potential of N. tabacum extracts obtained with NaDESs as antiaging and suggest their promising applications in the cosmetic and cosmeceutical industries. Full article

The incidence of Hashimoto’s disease (HD) increases with age and in people who have other autoimmune diseases. It is characterized by lymphocytic infiltration, fibrosis, and atrophy of the thyroid parenchyma with the simultaneous presence of thyroid peroxidase antibodies (ATPO) and/or thyroglobulin antibodies (ATG). Eicosanoids are formed via the cyclooxygenase (COX), lipoxygenase (LOX), and monooxygenase (CYP450) pathways with arachidonic acid (ARA), resulting in the production of epoxyeicosatrienoic acids (EETs) or hydroxyeicosatetraenoic acids (HETEs). These eicosanoids can act in an autocrine or paracrine manner on target cells. This study aimed to examine whether a gluten-free diet (GFD) can modulate the enzymatic pathways of the pro-inflammatory ARA cascade. The study material consisted of serum samples from Caucasian female patients with HD aged 18–55 years. Participants were enrolled in the study based on the presence of an ultrasound characteristic of HD, and elevated serum levels of anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies. Patients with confirmed celiac disease did not participate in the study. A total of 78 samples were analyzed, with 39 collected after 3 months of following a GFD. Eicosanoids (thromboxane B2, prostaglandin E2, leukotriene B4, and 16R-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid (16-RS HETE)) were extracted using high-performance liquid chromatography. The contribution of leukotriene (LTB) was analyzed in the LOX pathway, prostaglandins (PGE2) and thromboxane (TXB2) were selected for the involvement of the COX pathway, and 16RS HETE was used for the CYP450 pathway. All parameters were analyzed before and after a 3-month dietary intervention that included a gluten-free diet. In the obtained results, only one mediator, leukotriene B4, was significant (p < 0.05). The mean level on the initial visit was 0.202 ± 0.11 (SD), while it was 0.421 ± 0.27 (SD) on the subsequent visit, indicating a significant increase in its level after implementing a GFD. Although there was a trend in the CYP 450 pathway of decreased 16-RS HETE, the presented correlations show that thromboxane B4 and 16RS-HETE were positively correlated with the body mass and body fat mass of the examined patients. There was a trend in the CYP 450 pathway of decreased 16-RS HETE after GFD. Thromboxane B4 and 16RS-HETE levels before GFD were positively correlated with the body mass and body fat mass of the examined patients. A gluten-free diet in HD does not suppress the synthetic pathways of LOX, COX, or cytochrome P450 (CYP450). The level of adipose tissue has a greater impact on the inflammatory processes in HD than a gluten-free diet. This study does not confirm the suppressive effect of a gluten-free diet on the pro-inflammatory arachidonic acid cascade in any of the three analyzed mediator synthesis LOX, COX, CYP450 pathways. Full article

Terpenes represent a structurally diverse class of natural compounds with increasing scientific interest due to their potential anti-inflammatory properties. This study investigates the in silico binding behavior of six plant-derived terpenes—α-pinene, β-pinene, menthol, camphor, limonene, and linalool—against four key enzymes in the arachidonic acid (AA) metabolic pathway: cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and phospholipase A2 (PLA₂). AA serves as a reference for binding energy comparison. Blind rigid-body molecular docking is performed using AutoDock 4.2 and the Lamarckian Genetic Algorithm, with 100 runs per ligand–enzyme pair and the energy-based selection of optimal poses. The analysis includes binding energy (ΔG), inhibition constants (Ki), root-mean-square deviation (RMSD), and residue-level interactions. Several terpenes exhibit favorable binding energies and inhibition constants across the evaluated enzymes. For COX-1 and COX-2, menthol and camphor show low Ki values, indicating stable binding. Menthol and limonene also show the strongest affinities for PLA₂, exceeding AA. The focus is on compounds with potential to modulate arachidonic acid metabolism. In this context, β-pinene engages the catalytic site of PLA₂, linalool forms multiple contacts within key regions of 5-LOX, and menthol, α-pinene, and β-pinene align with functionally important regions in both COX isoforms. These targeted interactions suggest that the highlighted compounds may selectively interfere with enzymatic activity in inflammation-related pathways. By modulating key steps in AA metabolism, these terpenes may influence the biosynthesis of pro-inflammatory mediators, offering a promising avenue for the development of safer, plant-derived anti-inflammatory agents. The findings lay the groundwork for further experimental validation and the structure-based optimization of terpene-derived modulators. Full article

Background/Objectives: Medicinal plants such as Santolina chamaecyparissus L., an evergreen shrub from the Asteraceae family, have long been valued for their bioactive compounds and traditional therapeutic uses. Materials: In this study, the essential oil of S. chamaecyparissus (EOSC) was isolated via hydrodistillation and then comprehensively evaluated for its phytochemical composition and antioxidant, anti-inflammatory, hemolytic, and cytotoxic properties, as well as its in silico bioactivity. Results: In total, 89.5% of the essential oil composition was successfully identified using GC-MS analysis. Hydrocarbon sesquiterpenes constituted the largest fraction (36.0%), followed by oxygenated sesquiterpenes (19.7%). Phytochemical screening revealed high phenolic content (839.50 ± 5.0 mg GAE/g E.O), while the Total Antioxidant Capacity (TAC) assay confirmed its strong antioxidant potential. The oil showed moderate hemolytic activity and significant lipoxygenase inhibition, indicating anti-inflammatory capability. The cytotoxic effects of the EOSC were evaluated using the MTT assay and HepG2 liver cancer cells. A dose-dependent reduction in cell viability was observed, confirming the oil’s strong anticancer activity. Molecular docking and ADMET analyses supported the bioactivity of the identified compounds, which showed good drug-likeness and pharmacokinetic properties. Conclusions: These findings demonstrate that EOSC has promising antioxidant and anti-inflammatory properties, suggesting that it could have potential as a safe natural substance for use in drug development and food preservation. Full article

Neuroinflammation, triggered by lipoxygenase (LOX), contributes to Alzheimer’s disease (AD) progression. Overexpression of LOX-5 in patients with AD serum highlights its role. This study assessed the efficacy of the LOX-inhibitor-peptide YWCS in an AD rat model induced by Aβ_25–35 injection. Cognitive tests, magnetic resonance imaging (MRI) scans, and molecular analyses were conducted. YWCS treatment significantly improved cognitive function, as evidenced by improved performance in the open field, novel object recognition, elevated plus maze, and Morris water maze tests. MRI scans revealed hippocampal shrinkage in AD rats and no changes were observed from YWCS treatment. Molecular analysis revealed altered expression of LOX-5, LOX-12, Aβ, γ-secretase components, p-Tau¹⁸¹, Akt, p-Akt, and p53 in AD rats. Immunofluorescence staining confirmed increased expression of LOX, Aβ, and p-Tau¹⁸¹ in the hippocampus of AD rats, which was reduced by YWCS treatment. Serum LOX levels were elevated in AD rats and significantly decreased after YWCS treatment, aligning with previous findings in human AD patients and AD cell models. YWCS offered improvements in behavioral and inflammatory marker regulation and also prevented progression of the disease, as shown by MRI results. These results suggest that YWCS, by targeting LOX, has the potential to be a promising therapeutic agent for AD. Full article

Satureja montana L. (winter savory, family Lamiaceae) is an aromatic herb that is widespread throughout the Mediterranean region. In a prior study, the optimization of the green hydroxypropyl-β-cyclodextrin (HP-β-CD)-glycerol-assisted extraction procedure of S. montana was performed. As a result, four extracts abundant in total phenols (OPT-TP), total phenolic acids including rosmarinic acid (OPT-TPA-RA), total flavonoids (OPT-TF), and luteolin derivatives (OPT-LG) showing anti-elastase and anti-hyaluronidase properties, were prepared. Subsequently, we further explored the phytochemical, dermatological, and cosmeceutical potentials of these extracts, evaluating their antioxidant, anti-inflammatory, anti-tyrosinase, and anti-ultraviolet (UV) absorption activities. Furthermore, the biocompatibility of the extracts and their wound-healing properties were assessed using HaCaT cells. The results indicate that the extracts exhibited excellent antioxidant and cosmeceutical activities, which surpassed the activities of the employed standards in several assays (DPPH antiradical activity, β-carotene-linoleic acid, anti-lipoxygenase, anti-heat-induced ovalbumin coagulation, and UV absorbance assays). Furthermore, the extracts preserved more than 80% of the HaCaT cell viability at concentrations up to 62.5 µL extract/mL and also enhanced wound healing in the in vitro scratch wound-healing model. For example, the application of OPT-TP and OPT-TF led to 48.6% ± 3.3% and 48.6% ± 5.4% wound closure, respectively, after 48 h, compared to 34.8% ± 2.3% in the control group. The extracts exhibited excellent bioactivities, making them promising candidates for the development of cosmeceutical products, while their high biocompatibility indicates that they are suitable for direct application in cosmetics without prior solvent removal. Full article

The phenolic compounds present in wine industry by-products are a valuable source of biologically active ingredients that could be used in the development of functional foods. This manuscript investigates the potential of ultrasound-assisted extracts from Prokupac grape skins—a wine industry by-product—as functional food ingredients. Four extracts were prepared using different solvents and evaluated for their antioxidant, anti-inflammatory, and antimicrobial properties. Antioxidant activity was assessed through DPPH, ABTS, and FRAP assays, as well as EPR spectroscopy. Phenolic composition was determined via HPLC analysis, and anti-inflammatory potential was evaluated using a lipoxygenase inhibition assay. Results indicated that the extracts PSE3 (ethyl acetate) and PSE0 (direct extraction with 50% ethanol) exhibited superior antioxidant and anti-inflammatory activities, which can be attributed to their high polyphenolic content. Additionally, the extracts demonstrated antimicrobial effects against the tested microorganisms. These findings suggest that Prokupac grape skin extracts, particularly PSE3 and PSE0, could be valuable additions to functional foods, offering health benefits through their bioactive properties. Full article

Cannabis sativa L. has been traditionally used for its therapeutic properties, particularly in treating various skin conditions. This study explores the in vitro anti-aging potential of five distinct parts of C. sativa L. (inflorescence, seed, leaf, stem, and root) by analyzing their bioactive compounds and biological activities. Ultrasound-assisted extraction was employed using ethyl acetate as an extracting solvent, followed by chemical characterization via gas chromatography-mass spectrometry (GC-MS/MS) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS/MS) analyses. The biological assessment included antioxidant, anti-inflammatory, anti-tyrosinase activities, and cytotoxicity evaluations. The inflorescence extract demonstrated the antioxidant activity, with a half-maximal inhibitory concentration (IC₅₀) value of 3,849.01 ± 5.25 µg/mL against DPPH radicals and 31.19 ± 0.96% inhibition of NO radicals at 1.25 mg/mL. Notably, the stem extract exhibited the highest anti-tyrosinase activity, with an IC₅₀ value of 0.01 ± 0.00 mg/mL, and significantly inhibited 5-lipoxygenase (5-LOX) activity with an IC₅₀ value of <0.024 µg/mL. All extracts showed no cytotoxicity on HaCaT cells at a concentration of 10 µg/mL, indicating their potential safety for dermatological applications. The stem extract was abundant in phytosterols, triterpenoids, diterpenoids, unsaturated fatty acids, and phenolic compounds, which likely contribute to its anti-inflammatory and anti-tyrosinase effects. These findings suggest that the stem, traditionally considered as waste, could be a valuable raw material for developing dermatological treatments with strong anti-inflammatory and skin-brightening effects. Full article

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by impaired glucose regulation. This study evaluated the antioxidant and antidiabetic potential of aqueous extracts from four plant species from the southern Algarve: Aristolochia baetica, Chelidonium majus, Dittrichia viscosa, and Lavandula viridis, using non-cellular in vitro assays. HPLC/PDA was used to identify active compounds. Antioxidant activity was assessed by using TAA, FRAP, RP, and DPPH assays; antidiabetic potential through α-glucosidase and α-amylase inhibition; and wound healing relevance through elastase, collagenase, and lipoxygenase inhibition. D. viscosa showed the highest antioxidant activity (FRAP: 1132.99 ± 19.54 mg TE/g dw; DPPH IC₅₀ = 25.85 ± 0.75 μg/mL) and total phenolic/flavonoid content, with a diverse profile including caffeic and chlorogenic acids, isoquercetin, and quercetin. It also exhibited potent α-glucosidase inhibition (IC₅₀ = 0.61 ± 0.06 mg/mL), outperforming acarbose. L. viridis had the highest total phenolic content (39.04 mg/g), while A. baetica demonstrated the strongest anti-elastase, anti-collagenase, and lipoxygenase activity, suggesting wound-healing potential. C. majus showed the weakest effects. A strong correlation was observed between phenolic content and antioxidant/antidiabetic activity. These findings support further in vivo studies on D. viscosa and A. baetica for potential use in T2DM management and diabetic wound healing. Full article

Novel derivatives of valproic acid with biologically active moieties, such as thiomorpholine, 4-aminopyridine, serine methyl ester, trolox and the cinnamic acid derivative [(E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid], were synthesized at satisfactory yields. The conjugation of these moieties was based on the rationale of design and evaluation of compounds with selected structural characteristics, aiming at derivatives with multiple targets. These compounds reduced acute inflammation considerably and, in most cases, more than several highly used, well-known, non-steroidal anti-inflammatory drugs. They also offered the inhibition of soybean lipoxygenase, and some of them (compounds 5 and 6) possessed radical scavenging and lipid peroxidation attenuating effects. Their antioxidant capacity was several times higher than that of the established antioxidant trolox. All the tested compounds decreased plasma lipid markers in tyloxapol-induced hyperlipidemia in rats. Compound 2 resulted in 71.1%, 52.8% and 79.1% decrease in total cholesterol, triglycerides and LDL-cholesterol, respectively, at 150 μmol/kg (i.p.). The effect on total and LDL cholesterol is comparable or equal to that of simvastatin, a hypocholesterolemic 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitor, however, with additionally great triglyceride-decreasing effect compared to simvastatin. Thus, the synthesized compounds may be a valuable addition to multi-functional agents acting against various degenerative disorders that implicate inflammation and lipid derangement. Full article

Free radicals and inflammation have pivotal role in various degenerative diseases like cancer, rheumatoid arthritis, diabetes, cardiovascular and neurodegenerative disorders. Pyrazoles possess a wide range of biological activities such as antifungal, antituberculosis, antimicrobial, antiviral, anti-inflammatory, anti-convulsant, anticancer etc. In this present study a series of dibenzalacetones and the corresponding pyrazole hybrids were designed through bioisosterism, synthesized and biologically evaluated to highlight the importance of the extended conjugated system and substitution to the anti-inflammatory and antioxidant activity. The synthesis of dibenzalacetones was achieved via Claisen-Schmidt reaction. The dihydro-pyrazoles were synthesized from the substituted dibenzacetones and phenylhydrazines, hydrazine and semicarbazide under microwave irradiation optimizing reaction conditions. The synthesized compounds were spectroscopically characterized and evaluated for their anti-lipid peroxidation (AAPH) activity, their interaction with the free radical DPPH and the inhibition of soybean LOX. The novel derivatives were studied in terms of their physicochemical properties. Many of the dihydro-pyrazoles showed potent antioxidant properties and significant inhibition of soybean lipoxygenase as a result of their physicochemical features. Compounds 4a and 4b presented the most potent anti-lipid peroxidation abilities (98% and 97%), whereas compounds 2d and 2e have proved to be the most potent lipoxygenase inhibitors with IC₅₀ values 2.5 μM and 0.35 μM. Moreover, docking studies with soybean lipoxygenase highlight the interactions of the novel derivatives with the enzyme. Full article

The global prevalence of asthma is approximately 4.3%, and current asthma treatments focus on reducing symptoms, maintaining normal activity levels, and preventing the deterioration of lung function, rather than achieving a cure or complete prevention. We identified isochlorogenic acid C (ICGAC) as a potential natural medicine for the treatment of asthma. However, the bioavailability of ICGAC was low, ranging from 14.4% to 16.9%, suggesting the involvement of the gut microbiota. The full spectrum of ICGAC’s anti-asthmatic mechanism remains to be elucidated. This study investigated the mechanism by which ICGAC alleviates allergic asthma through the gut–lung axis. We discovered anti-asthma pathways and targets based on the selective regulation of lipid peroxidation and employed pharmacological tools to preliminarily validate their mechanisms and efficacy. To study the role of ICGAC in regulating the gut microbiota, we performed 16S rRNA gene sequencing and metabolite analysis. Furthermore, by combining molecular biology and lipid metabolomics, we elucidated the underlying anti-asthma mechanisms of ICGAC. The effective form of ICGAC varies between single and long-term administration. The oral administration of ICGAC enhances the gut-microbiota-derived production of short-chain fatty acids (SCFAs) as the active substances, modulates immune cell activity, influences the differentiation of T- and B-cells, and reduces airway inflammation. ICGAC also regulates the metabolic network of lipid mediators (LMs) and polyunsaturated fatty acids (PUFAs), thus exerting anti-inflammatory effects by modulating arachidonate lipoxygenase (ALOX) activity and LM levels. In addition, ICGAC enhanced the antioxidant response by upregulating the expression of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and nuclear factor erythroid 2-related factor 2 (Nrf2), while inhibiting the release of interleukin-4 (IL-4), thereby suppressing asthma inflammation and IgE production. The anti-asthmatic mechanism of oral ICGAC involves the inhibition of lipid peroxidation by chlorogenic acid (CGA) and SCFAs produced by the gut microbiota. ICGAC suppresses asthma-associated inflammatory and oxidative stress responses through the upregulation of GPX4, SLC7A11, and Nrf2 in lung tissue. This study not only provides a solid foundation for the potential clinical use of ICGAC in asthma treatment but also offers novel insights for future research and therapeutic strategies targeting asthma. Full article

Culinary herbs and spices are valued worldwide for their flavor, aroma, and medicinal benefits. They encompass diverse bioactive metabolites, such as polyphenols and terpenoids, which contribute to plant defense and offer anticarcinogenic, anti-inflammatory, antioxidant, and cognitive-enhancing effects. This study aimed to establish the volatile fingerprint of culinary herbs (lemon verbena, chives, basil, sage, coriander, and parsley) and spices (curcuma, nutmeg, cumin, black pepper, Jamaica pepper, and juniper berry) using headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME/GC-MS). The predominant volatile organic metabolites (VOMs) identified were subjected to in silico molecular docking simulations of anti-Alzheimer’s (e.g., acetylcholinesterase (AChE), butyrylcholinesterase (BChE)), antioxidants (e.g., monoamine oxidase B (MAO-B), inducible nitric oxide synthase (iNOS)), and anti-inflammatory receptors (e.g., 5-lipoxygenase (5-LOX), cyclooxygenase-2 (COX-2)). The culinary herb and spice extracts were also subjected to in vitro assays to evaluate their potential as antioxidant (DPPH, ABTS, and ORAC) and anti-inflammatory (% protein denaturation) agents. A total of 121 VOMs were identified in the culinary herbs and spices, with the predominant chemical families being monoterpenoids (48.3%), sesquiterpenoids (14.0%), esters (11.9%), and carbonyl compounds (8.8%). In silico molecular docking simulations revealed that cuminaldehyde, β-caryophyllene, γ-curcumene, germacrene D, and τ-cadinol exhibited the strongest inhibitory activities against the selected receptors. Among the extracts, Jamaica pepper showed the highest antioxidant and anti-inflammatory activities, while lemon verbena exhibited the lowest ones. These findings highlight the promising potential of the studied culinary herbs and spices in the modulation of inflammatory processes related to Alzheimer’s disease. However, further investigations, particularly clinical studies, are recommended to validate these results and explore their therapeutic applications. Full article

Several new coumarin–isoxazole–pyridine hybrids were synthesized through a 1,3-dipolar cycloaddition reaction of nitrile oxides, prepared in situ from pyridine aldehyde oximes, with propargyloxy- or propargylaminocoumarins in moderate-to-good yields. Synthetic modifications were applied using (diacetoxyiodo)benzene (PIDA) at room temperature, microwave irradiation, or tert-butyl nitrite (TBN) under reflux. Coumarin, isoxazole, and pyridine groups were selected for hybridization in one molecule due to their biological impact to inhibit lipid peroxidation and an enzyme implicated in inflammation. Preliminary in vitro screening tests for lipoxygenase (LOX) inhibition and anti-lipid peroxidation for the new hybrids were performed. A discussion on the structure–activity relationship is presented. Compounds 12b and 13a were found to be potent LOX inhibitors with IC₅₀ 5 μΜ and 10 μΜ, respectively, while 12b presented high (90.4%) anti-lipid peroxidation. Furthermore, hybrids 12b and 13a exhibited moderate-to-low anticancer activities on HeLa, HT-29, and H1437 cancer cells. Full article