Search Results (22,702)

Background: The pathogenesis of inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease is not well understood. This study investigated the roles and regulation of the claudin-1, -2, -3, and -4 isoforms in the pathogenesis of ulcerative colitis, and the potential therapeutic effects of nobiletin. Methods: Colitis was induced in rats by administering dextran sulfate sodium [DSS] in drinking water for seven days. Animals were treated daily with nobiletin [oral, 60 mg/Kg body weight] and studied in four groups, C [non-colitis control], D [DSS-induced colitis], CN [nobiletin-treated non-colitis control], and DN [nobiletin-treated DSS-induced colitis]. On day seven, the animals were sacrificed, and colonic tissues were collected and analyzed. Results: Both macroscopic and microscopic findings suggest the progression of colitis. In the inflamed colon, claudin-1 and -4 proteins were decreased, claudin-2 increased, while the claudin-3 protein remained unchanged. Except for claudin-1, these changes were not paralleled by mRNA expression, indicating a complex regulatory mechanism. Uniform β-actin expression along with consistent quality and yield of total RNA indicated selectivity of these changes. Nobiletin treatment reversed these changes. Conclusions: Altered expression of the claudin isoforms -1, -2, and -4 disrupts tight junctions, exposing the lamina propria to microflora, leading to electrolyte disturbance and the development of ulcerative colitis. Nobiletin with its anti-inflammatory properties may be useful in IBD. Full article

Osteoarthritis (OA) is an age-related disease characterized by inflammation, pain, articular cartilage damage, synovitis, and irreversible disability. Gynostemma pentaphyllum (Thunb.) Makino (GP), a herbal medicine traditionally used in East Asia for its anti-inflammatory properties, was investigated for its potential to modulate OA pathology and symptoms. This study evaluated GP’s efficacy in inhibiting pain, functional decline, and cartilage destruction in monosodium iodoacetate-induced OA and acetic acid-induced writhing models. Additionally, the effects of GP on OA-related inflammatory targets were assessed via mRNA and protein expression in rat knee cartilage and lipopolysaccharide-induced RAW 264.7 cells. The GP group demonstrated significant pain relief, functional improvement, and cartilage protection. Notably, GP inhibited key inflammatory mediators, including interleukin (IL)-1β, IL-6, matrix metalloproteinases (MMP)-3 and MMP-13, cyclooxygenase-2, and prostaglandin E receptor 2, surpassing the effects of active controls. These findings suggest that GP is a promising candidate for disease-modifying OA drugs and warrants further comprehensive studies. Full article

The improvement of mitochondrial function is described as a strategy for alleviating oxidative stress and intervening in the aging process. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is one of the major bioactive components isolated from Polygonum multiflorum Thunb, and it exhibits multiple activities, including antioxidant and anti-inflammatory effects. In this study, we found that 200 μM TSG significantly extended the mean lifespan of Caenorhabditis elegans by 16.48% and improved health status by delaying age-associated physiological decline in worms. The longevity prolongation effect of TSG depended on the regulation of the mitochondrial quality control process mediated by DAF-16/FOXO, SKN-1/Nrf2 and SIR-2.1/SIRT1 to improve mitochondrial function. Moreover, TSG treatment obviously alleviated the proteotoxicity of β-amyloid and tau proteins in worms. Our findings indicated that TSG is a promising natural product for preventing aging and treating aging-associated neurodegenerative diseases by regulating the mitochondrial quality control process to improve mitochondrial function. Full article

Plumeria rubra L. is an ornamental Caribbean plant widely known for its ethnobotanical uses and pharmacological activities. The ‘Tonda Palermitana’ cultivar, on which no data are to date available, is commonly cultivated in Sicily. The aim of our study was to characterize the micro-morphological features of leaves and flowers of this cultivar by light and Scanning Electron Microscopy and to investigate the phytochemical profile and the biological properties of their food-grade extracts (LE and FE, respectively) by LC-DAD-ESI-MS analysis and different in vitro assays. Numerous branched laticifers were observed, and their secretion contained alkaloids and lipophilic compounds as confirmed by histological analyses. Phytochemical analyses showed the presence of alkaloids (9%), terpenoids (13%) and fatty acids (6%), together with a very abundant presence of iridoids (28%) and polyphenols (39%). The most notable biological activity of both extracts appears to be the antioxidant one, showing half-inhibitory concentrations (IC₅₀) about 5 times lower than those detected in anti-inflammatory assays (383.74 ± 5.65 and 232.05 ± 2.87 vs. 1981.23 ± 12.82 and 1215.13 ± 10.15, for FE and LE, respectively), with LE showing the best, and statistically significant (p < 0.001), biological activity. These results allow us to speculate promising nutraceutical and cosmeceutical applications for this old Sicilian cultivar. Full article

The current study focuses on development of phospholipid complex-loaded films of etodolac for enhanced transdermal permeation and anti-inflammatory effect. An etodolac–phospholipid complex was developed using the solvent evaporation method and was characterized by DSC, XRD, FTIR, and ¹H-NMR studies. The formation of the complex led to conversion of a crystalline drug to an amorphous form. A stoichiometric ratio of 1:1 (drug–phospholipid) was selected as the optimized ratio. Further, the developed complex was incorporated into films and systematic optimization using a central composite design was carried out using a response surface methodological approach. The desirable design space based on minimum contact angle and maximum tensile strength was selected, while the water vapour transmission rate and swelling index were set within limits. The results for swelling index, contact angle, tensile strength, and water vapour transmission rate were 60.14 ± 1.01%, 31.6 ± 0.03, 2.44 ± 0.39 kg/cm², and 15.38 g/hm², respectively. These values exhibited a good correlation with the model-predicted values. The optimized formulation exhibited improved diffusion and permeation across skin. In vivo studies revealed enhanced anti-inflammatory potential of the developed films in comparison to the un-complexed drug. Hence, the study demonstrated that etodolac–phospholipid complex-loaded films improve the transdermal permeation and provided enhanced anti-inflammatory effect. Full article

Objective: Chondrocyte apoptosis has been considered a crucial mechanism that is responsible for cartilage destruction in osteoarthritis (OA). The mechanism of interleukin-37 (IL-37) on chondrocyte apoptosis has not been clearly determined in the pathogenesis of OA. Here, we explored the role of IL-37 in the regulation of cellular apoptosis in rat chondrocytes stimulated by IL-1β. Methods: Rat chondrocytes were used in in vitro study, and were stimulated with IL-1β (10 ng/mL) and/or recombinant IL-37 (rIL-37; 100 ng/mL) after cytotoxicity assessments using these cytokines were conducted. After rIL-37 treatment of chondrocytes stimulated with IL-1β, the cell proliferation assay, apoptosis assays, including expression of mitochondrial apoptosis-related markers, flow cytometry analysis of annexin V-FITC/propidium iodide (PI), cell cycle analysis, and Hoechst 33342 staining, and reactive oxygen species (ROS) measurement were used. Results: IL-1β induced expression of inflammatory cytokines and triggered degradation of the extracellular matrix of rat chondrocytes, but this effect was significantly attenuated by rIL-37 treatment. Enhanced ROS generation following IL-1β stimulation was reduced in a dose-dependent manner after stimulation with rIL-37. IL-1β induced pro-apoptotic markers and suppressed anti-apoptotic markers in rat chondrocytes. Flow cytometry using annexin V-FITC/PI revealed that IL-1β increased the apoptosis rate of rat chondrocytes, and that this effect was markedly reversed by treatment with rIL-37. Conclusions: IL-37 potently attenuated IL-1β-mediated apoptosis of rat chondrocytes by blocking ROS production. This study suggests that IL-37 can serve as a novel anti-cytokine therapy in OA by blocking chondrocyte apoptosis. Full article

The emergence of natural products has provided extremely valuable references for the treatment of various diseases. Cucurbitacin B, a tetracyclic triterpenoid compound isolated from cucurbitaceae and other plants, is the most abundant member of the cucurbitin family and exhibits a wide range of biological activities, including anti-inflammatory, anti-cancer, and even agricultural applications. Due to its high toxicity and narrow therapeutic window, structural modification and dosage form development are necessary to address these issues with cucurbitacin B. This paper reviews recent research progress in the pharmacological action, structural modification, and application of cucurbitacin B. This review aims to enhance understanding of advancements in this field and provide constructive suggestions for further research on cucurbitacin B. Full article

Waste from the agri-food chain represents a valuable reservoir of organic compounds with health-promoting properties. Momast Plus 30 Bio (MP30B) is a derivative obtained from olive-oil wastewater. Its enrichment in hydroxytyrosol (HT) via a patented technique has paved the way for its potential application as a dietary supplement in preventing cardiovascular diseases. MP30B demonstrates no significant alteration in cardiac and vascular parameters in “ex vivo” studies. However, it exhibits a strong ability to remove reactive oxygen species and exerts anti-inflammatory effects, notably reducing the concentration of iNOS and mitigating heart infections in “in vitro” experiments. Furthermore, MP30B slightly decreases the stiffness of the “ex vivo” thoracic aorta, potentially resulting in lowered arterial pressure and enhanced energy transfer to a normal ventricle. Based on these findings, we posit MP30B as a promising extract for cardiovascular disease prevention, and its specific antibacterial properties suggest its utility in preventing cardiac infections. Full article

Few therapeutic options are available to treat COVID-19. The KEAP1/NRF2 pathway, the major redox-responsive pathway, has emerged as a potential therapeutic target for COVID-19 as it regulates redox homeostasis and inflammation that are altered during SARS-CoV-2 infection. Here, we characterized the effects of NRF2-agonist Sulfodyne^®, a stabilized natural Sulforaphane, in cellular and animal models of SARS-CoV-2 infection. In pulmonary or colonic epithelial cell lines, Sulfodyne^® elicited a more efficient inhibition of SARS-CoV-2 replication than NRF2-agonists DMF and CDDO. This antiviral activity was not dependent on NRF2 but was associated with the regulation of several metabolic pathways, including the inhibition of ER stress and mTOR signaling, which are activated during SARS-CoV-2 infection. Sulfodyne^® also decreased SARS-CoV-2 mediated inflammatory responses by inhibiting the delayed induction of IFNB1 and type I IFN-stimulated genes in infected epithelial cell lines and by reducing the activation of human by-stander monocytes recruited after SARS-CoV-2 infection. In K18-hACE2 mice infected with SARS-CoV-2, Sulfodyne^® treatment reduced both early lung viral load and disease severity by fine-tuning IFN-beta levels. Altogether, these results provide evidence for multiple mechanisms that underlie the antiviral and anti-inflammatory activities of Sulfodyne^® and pinpoint Sulfodyne^® as a potent therapeutic agent against pathogenic effects of SARS-CoV-2 infection. Full article

Tea tree oil (TTO) improves the intestinal mucosal immunity of weaning piglets, but its underlying mechanism is not clear. We hypothesized that TTO may alleviate inflammatory injury by regulating the function of intestinal epithelial cells. Ileum epithelial cells (IPI-2I) were chosen and an inflammatory injury cell model was generated. The cell viability, cytokine secretion, and gene expression of TLR4 and NF-κB were measured to further evaluate the effects of TTO on the inflammatory injury in immune-stressed cells. The results showed that lipopolysaccharide (LPS; content: ≥30 μg/mL; time: 3 h, 6 h, or 9 h) decreased cell viability (p < 0.01), and 50 μg/mL LPS stimulated for 6 h resulted in an increased secretion of proinflammatory cytokines and a dramatically decreased secretion of anti-inflammatory cytokines (p < 0.05) in IPI-2I cells. Concentrations of 0–0.05% of TTO improved cell viability, while the 0.03% TTO treatment resulted in the highest cell viability and alleviated LPS-induced cell death (p < 0.01). In addition, 0.03% TTO alleviated the LPS-induced increase in the gene expression of IL-1β, TNFα, and IFNγ, as well as the decrease in the expression of IL-10 in IPI-2I cells (p < 0.05). LPS also upregulated the gene expression of TLR4 and NF-κB (p < 0.05); while TTO supplementation alleviated this effect (p < 0.05), 0.03% and 0.05% TTO supplementation had greater effects (p < 0.05). In conclusion, 50 μg/mL LPS stimulated for 6 h can be used to establish an immune-stressed cell model in IPI-2I cell lines, and 0.03% TTO treatment for 6 h alleviated inflammatory injury in the intestinal epithelial cells of pigs. Full article

Although frequently prescribed for frozen shoulder, it is not known if corticosteroid injections improve the course of frozen shoulder. This study aimed to assess the disease-modifying effects of an intra-articular corticosteroid administration at the freezing phase of frozen shoulder. Twenty-four Sprague-Dawley rats were divided into four groups. Their unilateral shoulders were immobilized for the first 3 days in all groups, followed by an intra-articular corticosteroid injection in Group A, an injection and the cessation of immobilization in Group B, no further intervention in Group C, and the cessation of immobilization in Group D. All rats were sacrificed in Week 3 of study, at which point the passive shoulder abduction angles were measured and the axillary recess tissues were retrieved for histological and Western blot analyses. The passive shoulder abduction angles at the time of sacrifice were 138° ± 8° (Group A), 146° ± 5° (Group B), 95° ± 11° (Group C), 132° ± 8° (Group D), and 158° ± 2° (Control). The histological assessments and Western blots showed greater fibrosis and inflammation in the groups that did not receive the corticosteroid injection (Groups C and D) compared to the corticosteroid-injected groups (Groups A and B). These findings demonstrate the anti-inflammatory and disease-modifying effects of corticosteroid injections during the freezing phase of frozen shoulder in an animal model. Full article

Repurposing saffron (Crocus sativus) waste presents a sustainable strategy for generating high-value products within the bioeconomy framework. Typically, flower components are discarded after stigma harvest, resulting in significant waste—350 kg of tepals per kilogram of stigmas. This research employed a comprehensive approach, integrating bioactivity studies (in vitro and in silico) with Life Cycle Assessment (LCA) evaluations, to extract and assess bioactive compounds from C. sativus tepals sourced in Tuscany, Italy. Phytochemical characterization using UPLC-MS/MS revealed a high abundance and variety of flavonoids in the hydro-ethanolic extract (CST). The antioxidant capacity was validated through various assays, and the ability to mitigate H₂O₂-induced oxidative stress and enhance fermentation was demonstrated in Saccharomyces cerevisiae. This study reports that C. sativus tepals extract reduces oxidative stress and boosts ethanol fermentation in yeast, paving the way for applications in the food and biofuels sectors. Further validation in RAW 264.7 macrophages confirmed CST’s significant anti-inflammatory effects, indicating its potential for pharmaceutical, cosmeceutical, and nutraceutical applications. In silico studies identified potential targets involved in antioxidant and anti-inflammatory processes, shedding light on possible interaction mechanisms with Kaempferol 3-O-sophoroside (KOS-3), the predominant compound in the extract. The integration of LCA studies highlighted the environmental benefits of this approach. Overall, this research underscores the value of using waste-derived extracts through “green” methodologies, offering a model that may provide significant advantages for further evaluations compared to traditional methodologies and supporting the circular bioeconomy. Full article

Chokeberries, which belong to the rose family (Rosaceae), have received increasing research attention due to their high content of secondary metabolites, especially oligomeric proanthocyanidins (OPCs). OPC-rich extracts are attributed to various positive health effects, including antioxidant or anti-inflammatory properties, which is why they are sold as food supplements. However, knowledge about the antioxidant properties of single OPCs is quite limited. Several separation steps with different separation techniques were performed to isolate OPCs from a pre-produced extract. More than 90 analytes were detected in the enriched fractions, which include eight OPCs, four cinchonains and one hexoside, including their respective isomers. For the characterization of the OPCs, high-resolution mass spectrometry coupled with liquid chromatography (LC-HRMS) was used. Based on the fragment spectra of the MS² experiments, conclusions about the fragmentation pathways and the structure of six new OPCs could be drawn. After isolating trimers, tetramers and pentamers, it was possible to test the antioxidant effect in relation to the individual degrees of polymerization (DP) or structures. The Trolox-equivalent antioxidant capacity (TEAC) test showed that all OPCs investigated exhibit antioxidant effects and a first correlation between the antioxidant effect and the DP could be postulated, which suggests new possibilities for the design of food supplements. Full article

In recent years, extensive research has focused on cannabidiol (CBD), a well-studied non-psychoactive component of the plant-derived cannabinoids. CBD has shown significant therapeutic potential for treating various diseases and disorders, including antioxidants and anti-inflammatory effects. Due to the promising therapeutic effect of CBD in a wide variety of diseases, synthetic derivatization of this compound has attracted the attention of drug discovery in both industry and academia. In the current research, we focused on the derivatization of CBD by introducing Schiff base moieties, particularly (thio)-semicarbazide and aminoguanidine motifs, at the 3-position of the olivetolic ring. We have designed, synthesized, and characterized new derivatives based on CBD’s framework, specifically aminoguanylhydrazone- and (thio)-semicarbazones-CBD-aldehyde compounds. Their antioxidant potential was assessed using FRAP and DPPH assays, alongside an evaluation of their effect on LDL oxidation induced by Cu²⁺ and AAPH. Our findings suggest that incorporating the thiosemicarbazide motif into the CBD framework produces a potent antioxidant, warranting further investigation. Full article

Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to bone marrow-derived mesenchymal stem cells (BM-MSCs) for potential clinical applications because of their accessibility and anti-inflammatory capacity. We previously demonstrated that DT-MSCs from dental pulp (DP-MSCs), periodontal ligaments (PDL-MSCs), and gingival tissue (G-MSCs) show immunosuppressive effects similar to those of BM, but to date, the DT-MSC-mediated immunoregulation of T lymphocytes through the purinergic pathway remains unknown. In the present study, we compared DP-MSCs, PDL-MSCs, and G-MSCs in terms of CD26, CD39, and CD73 expression; their ability to generate adenosine (ADO) from ATP and AMP; and whether the concentrations of ADO that they generate induce an immunomodulatory effect on T lymphocytes. BM-MSCs were included as the gold standard. Our results show that DT-MSCs present similar characteristics among the different sources analyzed in terms of the properties evaluated; however, interestingly, they express more CD39 than BM-MSCs; therefore, they generate more ADO from ATP. In contrast to those produced by BM-MSCs, the concentrations of ADO produced by DT-MSCs from ATP inhibited the proliferation of CD3⁺ T cells and promoted the generation of CD4⁺CD25⁺FoxP3⁺CD39⁺CD73⁺ Tregs and Th17⁺CD39⁺ lymphocytes. Our data suggest that DT-MSCs utilize the adenosinergic pathway as an immunomodulatory mechanism and that this mechanism is more efficient than that of BM-MSCs. Full article