Search Results (1,055)

Gingival inflammation compromises the integrity of the gingival epithelium and the underlying tissues, highlighting the need for adjuvant therapies with immunomodulatory and healing properties. Casearia sylvestris, a medicinal plant known as guaçatonga, is traditionally used to treat inflammatory lesions. This study aimed to investigate the effects of C. sylvestris on the synthesis of pro- and anti-inflammatory, proteolytic, and antioxidant molecules and on wound healing in epithelial cells. A human telomerase-immortalized gingival keratinocyte cell line (TIGKs) was used, and cells were exposed to Escherichia coli lipopolysaccharide (LPS) in the presence and absence of C. sylvestris extract, its diterpene-concentrated fraction, and its clerodane diterpene casearin J for 24 h and 48 h. Gene expression and protein synthesis were analyzed by RT-qPCR and ELISA, respectively. Nitric oxide (NO) and NF-κB activation were analyzed by Griess reaction and immunofluorescence, respectively. Additionally, cell viability was evaluated by alamarBlue^® assay, and an automated scratch assay was used for wound healing. LPS significantly increased the expression of cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-17), proteases (MMP-1 and MMP-13), iNOS as well as NO synthesis, and triggered NF-κB nuclear translocation. It also reduced IL-4 expression, cell viability, and cellular wound repopulation. Treatment with C. sylvestris derivatives significantly abrogated all aforementioned LPS-induced effects by 80–100%. Furthermore, even at higher concentrations, C. sylvestris did not affect cell viability, thus proving the safety of its derivatives. C. sylvestris exerts anti-inflammatory, antiproteolytic, and antioxidant effects on gingival keratinocytes, highlighting its potential as a valuable adjunct in the prevention and treatment of periodontal diseases. Full article

Bone tissue regeneration is a complex process that takes place at the level of osteoblasts derived from mesenchymal cells and occurs under the action of multiple signaling pathways and through the expression of osteoregenerative markers. The leaf extract of Juglans regia L. (JR) is rich in polyphenols with demonstrated osteoregeneration effects. In the present study, we investigated the extract’s effects on three types of cells with various stages of differentiation: adult mesenchymal stem cells (MSCs), osteoblasts at low passage (O6) and osteoblasts at advanced passage (O10). To assess the efficacy of the walnut leaf extract, in vitro treatments were performed in comparison with ellagic acid (EA) and catechin (CAT). The osteoregenerative properties of the leaf extract were evaluated in terms of cell viability, bone mineralization (by staining with alizarin red) and the expression of osteogenesis markers such as osteocalcin (OC), osteopontin (OPN), dentin matrix acidic phosphoprotein 1 (DMP1) and collagen type 1A. Another compound implicated in oxidative stress response, but also a bone homeostasis regulator, nuclear factor erythroid 2-related factor 2 (NRF2), was studied by immunocytochemistry. Together with collagen amount, alkaline phosphatase (ALP) activity and NF-kB levels were measured in cell lysates and supernatants. The obtained results demonstrate that JR treatment induced osteogenic differentiation and bone mineralization, and it showed protective effects against oxidative stress. Full article

Background: Inflammation and oxidative stress are key mechanisms in underlying skin conditions like psoriasis and eczema. While many plants, including Australian native plants, are proposed to target these pathways due to their phytochemical content, studies on whole extracts and their synergistic effects remain limited. Objectives: This study aimed to investigate individual and combined effects of whole plant extracts on skin protection and healing, focusing on their anti-inflammatory and antioxidant properties. Methods: The antioxidant potential of the individual and combined plant extracts were investigated on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and reactive oxygen species (ROS) assay followed by luciferase assay in MCF-7 AREc32 cells for nuclear factor erythroid 2-related factor 2 (Nrf2) activation. The anti-inflammatory activities were investigated on lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages for the inhibition of nitric oxide (NO), tumour necrosis factor (TNF)-α, and interleukin (IL)-6. Synergistic interaction was determined by the combination index model (CI < 1). Combination(s) showing synergistic and optimal activity were further investigated on LPS-induced human dermal fibroblasts (HDF) cells for IL-6 inhibition and wound healing activity. Results: Three of the tested Australian native plant extracts demonstrated prominent antioxidant and anti-inflammatory activities including bitter orange, mountain pepper berry and native river mint. In particular, their three-way combination (1:1:1, w/w) showed prominent synergistic (CI < 1) in reducing NO and IL-6, along with enhanced Nrf2 activation. In LPS-inflamed HDF cells, the combination maintained synergistic inhibition of IL-6 levels and promoted wound healing response. Conclusions: These findings highlight the therapeutic potential of Australian native plant as a whole extract for skin protection and repair attributed to antioxidant and anti-inflammatory activities. The observed synergistic anti-inflammatory and antioxidant effects support their use in the development of new cosmetic formulations for skin. Full article

Background: Alcohol-associated liver disease (ALD) is a primary global health concern, exacerbated by oxidative stress, inflammation, and gut barrier dysfunction. Conventional phytocompounds exhibit hepatoprotective potential but are hindered by low bioavailability. This study aimed to evaluate the hepatoprotective and gut-barrier-restorative effects of green-synthesized silver nanoparticles (AgNPs) derived from Enicostemma littorale, a medicinal plant known for its antioxidant and anti-inflammatory properties. Methods: AgNPs were synthesized using aqueous leaf extract of E. littorale and characterized using UV-Vis, XRD, FTIR, DLS, and SEM. HepG2 (liver) and Caco-2 (colon) cells were exposed to 0.2 M ethanol, AgNPs (1–100 µg/mL), or both, to simulate ethanol-induced toxicity. A range of in vitro assays was performed to assess cell viability, oxidative stress (H₂DCFDA), nuclear and morphological integrity (DAPI and AO/EtBr staining), lipid accumulation (Oil Red O), and gene expression of pro- and anti-inflammatory, antioxidant, and tight-junction markers using RT-qPCR. Results: Ethanol exposure significantly increased ROS, lipid accumulation, and the expression of inflammatory genes, while decreasing antioxidant enzymes and tight-junction proteins. Green AgNPs at lower concentrations (1 and 10 µg/mL) restored cell viability, reduced ROS levels, preserved nuclear morphology, and downregulated CYP2E1 and SREBP expression. Notably, AgNPs improved the expression of Nrf2, HO-1, ZO-1, and IL-10, and reduced TNF-α and IL-6 expression in both cell lines, indicating protective effects on both liver and intestinal cells. Conclusions: Green-synthesized AgNPs from E. littorale exhibit potent hepatoprotective and gut-barrier-restoring effects through antioxidant, anti-inflammatory, and antilipidemic mechanisms. These findings support the therapeutic potential of plant-based nanoparticles in mitigating ethanol-induced gut–liver axis dysfunction. Full article

Background/Objectives: Thousands of nephrectomies are performed annually in the United States, but the short-term metabolic effects of surgically induced renal ischemia remain unclear. The conventional metabolic markers used to characterize post-surgical renal function, such as creatinine and GFR, are measured in the serum but do not provide metabolic information about the renal parenchyma itself. We aimed to characterize the immediate metabolic effects of surgical ischemia on renal parenchyma within a temporal framework. Methods: Timed renal parenchyma biopsies were collected from eight patients undergoing nephrectomy for renal cell carcinoma both prior to and after ligation of the renal hilum. These samples were ground, extracted, and analyzed using nuclear magnetic resonance (NMR) spectroscopy to measure changes in lactate, succinate, glucose, alanine, and glycine levels. Results: Due to experimental limitations, we were only able to draw limited conclusions from three patients. Of the five remaining patients, all had significant increases in lactate and succinate levels as a function of time, though the degree to which these increases occurred varied between each patient. Glucose levels generally decreased in the renal parenchyma but did not necessarily correlate with lactate production, assuming all glucose underwent fermentation to lactate in a hypoxic environment. Alanine and glycine levels did not change in a predictable pattern across patients. Conclusions: There are significant changes in lactate, glucose and succinate levels within minutes of the onset of renal ischemia in human patients. The degree of change in the metabolites analyzed varied significantly between patients. The length of surgical ischemia must be considered during surgical procurement of tumor specimens for metabolomic analysis. Full article

Oxidative stress, which contributes to neuronal cell dysfunction, is a critical factor in the pathogenesis of neurodegenerative diseases. Anthocyanins and α-tocopherol have shown potential in mitigating oxidative damage, and their combination may provide synergistic effects. This study investigated the combined effects of a cyanidin-3-glucoside (C3G)-enriched extract derived from Oryza sativa L. cv. RD83 and α-tocopherol (C3GE) on hydrogen peroxide (H₂O₂)-induced oxidative stress in SH-SY5Y cells. Cells were treated with C3GE during exposure to 200 µM H₂O₂. Cell viability, intracellular reactive oxygen species (ROS), and oxidative stress biomarkers, including the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as malondialdehyde (MDA) levels, were evaluated. Protein expression levels of histone deacetylase 1 (HDAC1), nuclear factor erythroid 2 related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and SOD1 were also assessed. The combined treatment markedly improved cell viability, suppressed ROS accumulation, enhanced antioxidant enzyme activities, and significantly reduced MDA levels, suggesting effective protection against oxidative damage. Mechanistically, C3GE downregulated HDAC1 expression while upregulating Nrf2, HO-1, and SOD1, indicating that its antioxidant and neuroprotective effects are mediated, at least in part, through epigenetic modulation of redox-related signaling pathways. These results demonstrate a synergistic interaction between C3G and α-tocopherol that enhances cellular antioxidant defenses and supports redox homeostasis. In conclusion, the C3GE combination offers a promising therapeutic approach for preventing or attenuating oxidative stress-induced neuronal injury, with potential relevance for the treatment of neurodegenerative disorders. Full article

Psoriasis is a chronic inflammatory skin disease characterized by erythema, infiltration, and scaling, which is mainly caused by interleukin (IL)-17. The use of molecular targeted drugs in specific therapies offers high efficacy; however, high medical costs and a significant risk of side effects highlight the need for novel therapeutic agents. We previously observed that Morus alba extract (MAE) suppressed IL-17-induced CCL20 mRNA expression in normal human epidermal keratinocytes (NHEKs). In this study, we focused on the IL-17 signaling pathway and investigated the effects of pentacyclic triterpenoids, betulinic acid (BA), and ursolic acid (UA), which are present in MAE, on NHEK cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) revealed that both BA and UA suppressed CCL20 expression, while only UA alone inhibited CCL20 release. ELISA using specific inhibitors demonstrated that both the p38 and extracellular-signal-regulated kinase 1/2 (ERK1/2) pathways were crucial for IL-17-induced CCL20 release in NHEK. UA effectively suppressed ERK1/2 nuclear localization and moderately affected p38 phosphorylation. These results indicated that UA is a potential seed compound for psoriasis treatment through its targeting of the IL-17 pathway. Full article

Malaria is a parasitic infectious disease that is endemic in many tropical countries. Even though several effective antimalarial agents have been implemented, treatment failure still occurs, and malaria continues to cause neurological complications and death, particularly in severe or drug-resistant cases. Hence, novel therapeutic agents with distinct mechanisms of action, as well as alternative chemical compounds that can overcome resistance, are still needed to improve malaria therapy. This study aimed to investigate the antimalarial activities of Brucea javanica, a tropical plant extracts against Plasmodium falciparum, the major species associated with severe malaria. In this study, malaria parasites were treated with plant extracts using single and co-incubation methods, along with artesunate and chloroquine, and their inhibitory effect on parasite development was determined by microscopy. The results show that all tested doses of the extracts that effectively inhibited malaria parasites did not cause hemolysis of red blood cells (RBCs). The root extract (RE) and fruit extract (FE) inhibited parasite growth at IC₅₀ values of 0.41 ± 1.14 µg/mL and 0.26 ± 1.15 µg/mL, respectively. These plant extracts significantly interrupted malaria development at the ring stage, as presented by a reduction in the conversion rate to trophozoites and schizonts. The defective parasites treated with plant extracts were characterized by nuclear clumping, leading to pyknotic cell death. Moreover, RE and FW extracts elicited an additive effect with artesunate and chloroquine, significantly reducing IC₉₀ levels for the inhibition of parasite development. In conclusion, B. javanica extracts inhibited the asexual blood-stage development of malaria parasites. They distinctively show the additive effects of ATS and CRQ, elucidating their potential for further studies on novel formulas of antimalarial drug regimens. Full article

Immunotherapy is a transformative strategy in oncology, yet the development of novel immunomodulatory agents remains essential. This study explores the anti-tumor potential of a structurally unique polysaccharide isolated from an Aspergillus ochraceus (AOP), sourced from the Antarctic Weddell Sea. Using alkaline-assisted extraction and chromatographic purification, we obtained a homogeneous polysaccharide predominantly composed of galactose and mannose, with an average molecular weight of 39.67 kDa. The structure was characterized by an integrated nuclear magnetic resonance spectroscopy and mass spectrometry analysis, revealing that the AOP is composed of β (1→5)-linked galactofuranose units, with a minor substitution by α-D-mannopyranose residues via (1→2) glycosidic bonds at the C2 of the galactofuranose. Functional assays, including CCK8 and wound-healing tests, demonstrated that this polysaccharide, referred to as AOP, inhibited melanoma cell proliferation and migration in a dose-dependent manner. Additionally, the AOP activated RAW264.7 and bone marrow-derived macrophage (BMDM) cells without exhibiting significant cytotoxicity, leading to the release of inflammatory factors such as TNF-α, IL-1β, and IL-6. Mechanistically, the AOP was found to upregulate the expression of CD86 and IFN-γ, while downregulating genes like IL-4 and Arg1. These findings position the AOP as the first documented Antarctic fungal polysaccharide with macrophage-reprogramming capabilities against melanoma, offering novel molecular insights for marine-derived immunotherapeutics. Full article

Androgenetic alopecia (AGA) is associated with dihydrotestosterone (DHT)-induced apoptosis in human dermal papilla cells (HDPCs) via androgen receptor (AR) upregulation. This study aimed to evaluate the potential of Cucumis melo var. makuwa leaf extract (CLE) to attenuate these DHT-mediated effects in HDPCs. HDPCs were treated with CLE, and DHT-induced apoptosis and AR expression were assessed. High-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC–ESI–MS) identified Meloside A as the principal bioactive constituent within CLE. CLE significantly attenuated DHT-induced apoptosis in HDPCs, demonstrating a 57.74% reduction at 1000 ppm. Mechanistically, Meloside A inhibited DHT-stimulated AR nuclear translocation and reduced AR protein expression. Furthermore, Meloside A decreased the expression of downstream target genes at 100 ppm, showing a 16.27% reduction in IL-6, a 26.55% reduction in TGF-β1, and a 35.38% reduction in DKK-1. Additionally, Meloside A significantly inhibited ROS generation within DHT-stimulated HDPCs by 45.45% at 100 ppm. These findings suggest that Meloside A, isolated from CLE, exerts anti-AGA effects by modulating AR nuclear translocation and gene expression. This highlights its potential as a therapeutic agent for AGA and provides a basis for developing novel therapeutic strategies for hair loss. Full article

Dysregulated expression of nuclear receptor superfamily 4 group A member 2 (NR4A2) has recently been associated with autistic spectrum disorder (ASD), speech impairment, and neurodevelopmental delay (NDD); however, its precise role in the prevalence and etiopathogenesis of ASD has not been fully elucidated. Herein, we aimed to explore the role of NR4A2 variants in the genetic underpinnings of ASD among Saudi children of different age ranges and phenotype severities. A total of 338 children with ASD from 315 unrelated families (293 simplex, 2 quads, and 1 quintet) were screened for NR4A2 variants via exome sequencing (ES) of the genomic DNA extracted from peripheral blood mononuclear cells (PBMCs), after which the probands with identified NR4A2 variants were further subjected to trio genetic analyses. ES analysis revealed 10 de novo NR4A2 variants (5 indels/nonsense, 2 missense, and 3 variants affecting splicing) in 8 unrelated probands (2.37%) and 2 affected siblings from 8 unrelated families (6 simplex (2.04%) and 2 quads (8.7%)). Three NR4A2 variants were notably recurrent among both affected and unaffected carriers. All identified indels and two splicing variants met the criteria for pathogenic/loss-of-function (LoF) variants according to the ACMG classification (PVS1), whereas the missense variants were classified as of uncertain significance (VUS). This study is among the first to identify such a high frequency of recurrent variants in an ASD cohort, suggesting their significant contribution to the etiopathogenesis of ASD within this population. Full article

Nanotechnology offers alternative approaches to the discovery of anticancer drugs. Hydrophobic bioactive components can be included in the cores of amphiphilic nanocarriers, which leads to the formation of a water-dispersible product with improved bioavailability, facilitated excretion, and reduced systemic toxicity in the treated organisms. This study was aimed at the formation of polymer nanocarriers, loaded with anticancer drug precursor podophylotoxin (PPT) or PPT-containing juniper leaf extracts, seeking to study their antineoplastic activity in A-431 epidermoid carcinoma cells and HaCaT normal keratinocytes. The amphiphilic, biodegradable, and biocompatible MPEG-b-PLA diblock copolymer was self-assembled in aqueous media into nanosized particles, whose physicochemical characteristics were studied by dynamic light scattering, transmission electron microscopy, and other methods. High encapsulation efficiency was determined for the PPT component-loaded micelles. DNA fragmentation, cell cycle arrest, nuclear condensation, membrane lipid order assessment, reactive oxygen species, and apoptosis induction by the loaded nanocarriers in A-431 or HaCaT cells were analyzed by the comet assay, FACS, Hoechst DNA staining, Laurdan generalized polarization, and other methods. As a result of various cellular processes induced by the PPT component-loaded nanoparticles, effector caspase-3 and caspase-7 activation showed selectivity towards tumor cells compared to the normal cells. The newly obtained PPT-containing nanoparticles have applications as potential drugs in the prospective nanomedicine. Full article

The World Health Organization notes that some bacteria have been demonstrated to possess significant public health risks; they have antibiotic resistance, and there are fewer alternatives for control. The n-hexane extract and cinaguaiacin obtained from Artemisia cina show promising antibacterial activity, including against multidrug-resistant bacteria that affect animal and human health. Objective: The aim of this study was to determine the antibacterial activity of the n-hexane extract of A. cina and cinaguaiacin against multidrug-resistant bacteria. Methods:A. cina was collected in the pre-flowering period, the n-hexane extract was obtained, and chromatographic techniques and structure were used to separate the lignans, which were elucidated with nuclear magnetic resonance techniques. Four ATCC strains were used, and four strains were isolated from clinical cases with different resistance profiles. The antibacterial activity was determined by calculating the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), the time-kill kinetics assay, and the cell membrane integrity and DNA release assay. Molecular docking studies of lignans demonstrated the binding mode involved in the active site of DNA gyrase B. Results: The n-hexane extract inhibited growth against 87.5% of the strains tested (MIC 5.31 to 42.5 mg/mL) and showed bactericidal activity against 25% of the strains tested (MBC 0.62 to 85 mg/mL). Cinaguaiacin inhibited growth against 100% of the strains tested (MIC, 0.56 to 2.25 mg/mL) and exhibited bactericidal activity against 25% of the strains tested (MBC, 0.62 to 85 mg/mL). Conclusions: The mechanism of cinaguaiacin’s action may be associated with damage to the plasma membrane, as the protein and DNA levels were higher than those of the positive control. The n-hexane extract and cinaguaiacin obtained from A. cina showed a bacteriostatic or bactericidal effect, depending on the strain evaluated. Full article

Caulebra okamurae (C. okamurae), a green seaweed, has been reported to exhibit pharmacological properties, including anti-obesity and anti-diabetic effects. This study investigated the anti-inflammatory effects of C. okamurae extracts on periodontal health. The cell viability of RAW 264.7 macrophages was dose-dependently assessed using an MTS assay. The anti-inflammatory activity of C. okamurae on Porphyromonas gingivalis (P. gingivalis)-stimulated RAW 264.7 macrophages was evaluated by measuring nitric oxide (NO) production. mRNA expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were quantified via quantitative real-time PCR (qRT-PCR). The protein expression of iNOS, p-IKKα/β, p-IκBα, and NF-κB p65 was examined using Western blot and immunofluorescence. The results demonstrated that C. okamurae extracts exhibited no cytotoxicity in RAW 264.7 macrophages at concentrations of 0.2, 2, 20, and 200 μg/mL. The extracts dose-dependently reduced NO production, downregulated mRNA levels of proinflammatory cytokines, and inhibited iNOS expression in P. gingivalis-stimulated RAW 264.7 macrophages, a model commonly used to study periodontal inflammation. Furthermore, the extracts suppressed the phosphorylation of IKKα/β and IκBα and prevented the NF-κB p65 nuclear translocation. These findings suggest that C. okamurae extracts inhibit NF-κB signaling activation triggered by the periodontal pathogen, highlighting their potential anti-inflammatory effects, relevant to periodontal disease. Full article

The edible mushroom Coprinus comatus has a long history of use in metabolic diseases, which is increasingly documented by modern research. Due to its favorable nutritional composition, it was assumed that this mushroom could accelerate tissue recovery after acutely induced damage with subsequent disturbance of primarily carbohydrate metabolism. To test this hypothesis, the alloxan diabetes model was used, where experimental animals’ change in body weight and biochemical and histological indicators of recovery were monitored. Before performing the in vivo part, HPLC analysis of the C. comatus extract was carried out with subsequent in silico and in vitro tests. Comparing the animals treated with the mushroom in three different doses, no significant change in body weight was observed. Still, the change was also noticed in the lipid status and glycemia, with a dose-dependent beneficial effect. Morphometric analysis of pancreatic tissue stained by immuno-histochemical methods showed that long-term treatment with C. comatus leads to increased numerical density, nuclear volume, and absolute number of beta cells of the islets of Langerhans, which suffered severe damage after alloxan administration. Overall, C. comatus may contribute to faster tissue recovery after acute diabetic-relevant damage with chronic consequences. Full article