Search Results (4,992)

Turnera subulata is traditionally used to treat inflammatory and infectious conditions; however; its biological activities remain incompletely characterized. In this study, aqueous (AETS) and hydroethanolic (HETS) extracts obtained from the aerial parts (leaves, stems, and flowers), as used in traditional infusions, were compared regarding physicochemical composition, redox behavior, cytotoxicity, immunomodulatory, and antimicrobial activities. HETS showed significantly higher phenolic content (2555.96 ± 43.55 mg GAE/100 mL) compared to AETS (1269.54 ± 20.60 mg GAE/100 mL) and exhibited stronger DPPH (83.05 ± 0.05%) and ABTS (85.1 ± 1.5%) radical scavenging activity. In contrast, AETS showed greater antioxidant capacity in the TRAP assay from 50 µg/mL (p < 0.0001). Both extracts displayed dose-dependent pro-oxidant behavior in the deoxyribose/Fenton system. In vitro assays demonstrated that both extracts exhibited dose-dependent cytotoxicity in SH-SY5Y cells, with no significant cytotoxic effects observed at concentrations ≤ 50 µg/mL. HETS significantly increased IL-10 levels (p < 0.05), indicating immunomodulatory activity. In antimicrobial assays, HETS showed selective activity against Staphylococcus aureus, with MIC values ranging from 0.625 to 1.25 mg/mL, while no relevant inhibition was observed against Escherichia coli. No synergistic interaction with vancomycin was detected. Overall, the results indicate that the extraction solvent strongly influences the phenolic enrichment and biological activity. The hydroethanol extract showed the most consistent bioactivity, highlighting its potential for applications as a natural antioxidant, immunomodulatory, and anti-staphylococcal agent. Future studies should focus on compound isolation, mechanistic validation, and evaluation in in vivo models to support potential commercial and therapeutic applications. Full article

Gelatin methacrylate (GelMA) hydrogels are promising carriers for bioactive agents like curcumin (Cur) and adenosine diphosphate (ADP) in wound healing. However, existing GelMA-based systems fail to achieve both rapid hemostasis and sustained anti-inflammatory effects. In this study, we developed a Cur/ADP GelMA hydrogel, and evaluated its anti-inflammatory, regenerative, hemostatic, and biocompatible properties. Proton nuclear magnetic resonance (¹H-NMR) analysis showed that a 65% degree of substitution of GelMA is optimal for wound dressings. Scanning electron microscopy revealed a uniform pore size, aiding inflammatory exudate removal. The Cur/ADP GelMA hydrogel exhibited strong adhesion, stability, and antibacterial activity, reducing E. coli and S. aureus proliferation by 85% and 72%, respectively. Hemostatic effects were observed, with blood loss reduced to 238 ± 23 mg compared to 559 ± 18 mg in the untreated group. The ELISA results showed reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and increased IL-10. In vivo studies demonstrated 98% wound closure by day 14, enhanced granulation tissue formation, and a 70% thicker epidermis compared to controls. Mechanistically, ADP accelerates platelet activation and clot formation, while Cur modulates the inflammatory microenvironment, enabling synergistic hemostasis and immune regulation, thus promoting accelerated wound healing. Full article

Plant-derived bioactive metabolites have emerged as promising modulators of oxidative stress and inflammation, two interconnected processes involved in the pathogenesis of numerous chronic diseases. Arid ecosystems, particularly the Sonoran Desert, constitute an underexplored source of structurally diverse phytochemicals with significant pharmacological potential. This review provides a comprehensive overview of major classes of plant-derived bioactives, including polyphenols, flavonoids, terpenoids, and alkaloids, with emphasis on their molecular mechanisms of antioxidant and anti-inflammatory action. These compounds exert cytoprotective effects through direct reactive oxygen species (ROS) scavenging and indirect regulation of endogenous defense systems, primarily via activation of the Nrf2/Keap1 pathway and suppression of NF-κB signaling. Additional pathways, including MAPK, PI3K/Akt, AMPK, and mitochondrial regulatory networks, are discussed as critical mediators of redox balance and inflammatory control. Particular attention is given to Sonoran Desert plant species such as Bucida buceras, Phoradendron californicum, Larrea tridentata, Opuntia spp., and Agave deserti, all of which demonstrate promising biological activities associated with enhanced adaptation to environmental stress. Experimental approaches used to evaluate phytochemical bioactivity, including chemical assays, cellular models, omics technologies, and translational strategies, are also examined. Furthermore, this review discusses current limitations related to bioavailability, phytochemical variability, and clinical validation, highlighting emerging nanodelivery systems and precision medicine approaches as potential solutions. Collectively, the evidence supports the therapeutic relevance of Sonoran Desert plant bioactives as multi-target agents for modulating oxidative stress, inflammation, and chronic disease progression Full article

Excessive accumulation of reactive oxygen species from exogenous and endogenous stressors can cause cellular damage. Chlorella contains diverse bioactive compounds, and violaxanthin, a major carotenoid pigment found in Chlorella sp. HS-V, has been reported to possess anti-inflammatory, anticancer, and antioxidant properties. We investigated the effect of violaxanthin on hydrogen peroxide (H₂O₂)-induced oxidative stress in human keratinocytes. Chlorella sp. HS-V extract significantly restored the H₂O₂-induced decrease in cell viability. Similarly, violaxanthin reduced H₂O₂-induced cytotoxicity and intracellular reactive oxygen species levels, which was associated with the upregulation of antioxidant enzyme expression. Under H₂O₂-induced oxidative stress conditions, violaxanthin may enhance cellular antioxidant defense by promoting nuclear factor erythroid 2-related factor 2 (NRF2) translocation through the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3β (PI3K/AKT/GSK3β) signaling pathway. Additionally, violaxanthin improved H₂O₂-impaired wound healing in HaCaT human keratinocyte cells and reduced senescence-associated beta-galactosidase-positive normal human epidermal keratinocytes. Overall, these findings suggest that violaxanthin may serve as a potential therapeutic agent for mitigating oxidative stress-induced cellular dysfunction. Full article

Black mustard (Brassica nigra L.) seeds are a rich source of bioactive phytochemicals; however, their antioxidant, antibacterial, and anti-inflammatory potential has not been comprehensively explored. Therefore, this study aimed to assess antioxidant, antibacterial, and anti-inflammatory effects of black mustard seed extracts obtained from Soxhlet extraction with hexane (HE) and ethanol (EE), and ultrasonic-assisted ethanolic (UE) extraction. HPLC analysis confirmed the presence of sinapic acid in all extracts. Phytochemical profiling revealed that the EE was enriched in phenolic compounds, while the UE exhibited a higher flavonoid content. Accordingly, both EE and UE demonstrated strong antioxidant activities, including radical scavenging capacity, reducing power, and inhibition of lipid peroxidation. All extracts demonstrated antibacterial activity against Staphylococcus epidermidis. The anti-inflammatory potential of extracts was supported by the inhibition of lipoxygenase and protease. The UE showed the strongest lipoxygenase inhibition, while the EE and UE exhibited comparable protease inhibitory effect. Regarding RAW264.7 cells, the extracts were non-cytotoxic and reduced the expression of IL-6 and IL-31. Molecular docking analysis suggested that sinapic acid contributes to the anti-inflammatory activity through interactions with key inflammatory targets. Overall, the EE and UE demonstrated multitarget antioxidant, antibacterial, and anti-inflammatory activities, supporting their potential application in functional and dermatological formulations for inflammation management. Full article

Influenza A virus (IAV) remains a major global health threat despite available vaccines and antiviral agents, while current therapies are limited by drug resistance and safety concerns. Curcuminoids exhibit antiviral and anti-inflammatory activities but are constrained by poor water solubility and low bioavailability. To address these limitations, we investigated the antiviral and immunomodulatory properties of a water-solubilized curcuminoid nanoparticle formulation (C–S/M) in both in vitro and in vivo models of IAV infection. To evaluate the potential antiviral and anti-inflammatory effects of C–S/M, we performed a cytopathic effect (CPE) reduction assay in triplicate at 0.001 MOI and quantitative real-time PCR (qRT-PCR) targeting viral NS1 transcripts in MDCK cells. C–S/M suppressed viral NS1 vRNA levels in MDCK cells at lower curcuminoid-equivalent concentrations than native curcuminoids and attenuated IAV-induced TNF-α, IL-6, and IL-8 production. Furthermore, in vivo antiviral efficacy was evaluated in female C57BL/6 mice intranasally infected with IAV and treated orally with C–S/M. Survival, lung viral loads, pulmonary cytokine levels, and splenic immune cell phenotypes were analyzed. In IAV-infected mice, oral administration of C–S/M modestly improved survival and significantly reduced lung viral burden and pulmonary proinflammatory cytokine levels. In addition, in vivo C–S/M treatment was associated with recovery of virus-suppressed T-cell immune responses, including increased Th1 and activated CD8⁺ T cells, reduced regulatory T-cell expansion, and restoration of multifunctional CD4⁺ and CD8⁺ T cells. These findings suggest that C–S/M exerts antiviral and immunomodulatory effects in experimental IAV infection and may serve as a potential adjunctive candidate for further investigation against influenza-associated inflammation. Full article

Kawasaki disease (KD) represents the foremost cause of acquired pediatric heart disease, with coronary artery injury being the principal factor contributing to adverse prognoses. A significant clinical challenge is that 20–30% of patients demonstrate resistance to intravenous immunoglobulin (IVIG), which markedly elevates the risk of coronary artery lesions and long-term cardiovascular sequelae. Consequently, there is an urgent need to investigate novel pathogenic mechanisms beyond the conventional cytokine storm theory and to identify effective therapeutic targets. This review systematically summarizes the key role of the autophagy–inflammation axis in KD vasculopathy. Current evidence indicates that defective mitophagy and lysosomal dysfunction induce mitochondrial DNA release, resulting in overactivation of the NLRP3 inflammasome and cGAS-STING pathways, which amplify inflammatory responses and aggravate endothelial damage. The regulation of this axis is dynamic during both the acute and recovery phases and is influenced by metabolic reprogramming and epigenetic modifications, which may partially explain the lack of response to IVIG. Pharmacological agents, such as rapamycin and metformin, as well as natural compounds, such as resveratrol and urolithin A, have demonstrated beneficial anti-inflammatory effects in preclinical studies. Targeting the autophagy–inflammation axis represents a significant research direction with the potential to evolve into a promising therapeutic strategy. Mechanistically, restoring the balance of the autophagy–inflammation axis holds promise for mitigating coronary complications and improving long-term cardiovascular outcomes in children with KD; however, this prospect requires validation through prospective clinical studies. Full article

Background: Pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor with potent antioxidant and anti-inflammatory properties, has been shown to protect against cardiac injury. However, its therapeutic potential in diabetic cardiomyopathy (DCM) induced by Type 2 diabetes mellitus (T2DM) and the underlying mechanisms remain poorly understood. Methods: A T2DM mouse model was established via a high-fat diet and low-dose STZ. We investigated the cardioprotective effects of 12-week oral PQQ administration, assessing fasting blood glucose, oral glucose tolerance, cardiac function, myocardial histopathology, blood biochemistry, mitophagy, and NLRP3 inflammasome activation. In vitro experiments using AC16 cardiomyocytes exposed to palmitic acid and high glucose were also conducted. Results: Results showed PQQ significantly improved cardiac function, attenuated remodeling, and reduced proinflammatory cytokines in mice with T2DM, regulated key mitophagy-related proteins (Parkin, Beclin-1, LC3B-II, p62), and downregulated NLRP3 inflammasome pathway components (Caspase-1, NLRP3, IL-1β, IL-18). In vitro experiments demonstrated that PQQ reduced reactive oxygen species (ROS) production, improved mitochondrial membrane potential, promoted mitophagy, and inhibited NLRP3 inflammasome-mediated pyroptosis. Conclusions: PQQ alleviates DCM in mice with T2DM by improving mitochondrial quality control, promoting mitophagy, and subsequently inhibiting NLRP3 inflammasome-mediated pyroptosis, highlighting its potential as a promising therapeutic agent for T2DM-associated cardiomyopathy. Full article

Crohn’s disease (CD) is a chronic immune-mediated inflammatory disorder characterized by transmural inflammation and a progressive course that frequently leads to structural complications such as intestinal fibrosis. Fibrostenosing disease represents a major clinical challenge, affecting up to 50% of patients over time and often requiring surgical intervention. Despite advances in anti-inflammatory therapies, no effective treatments currently exist to prevent or reverse established fibrosis. Intestinal fibrosis arises from a dysregulated tissue remodeling process driven by excessive extracellular matrix deposition and persistent activation of mesenchymal cells, particularly fibroblasts and myofibroblasts. This process is orchestrated through complex interactions between immune and non-immune cells and mediated by key signaling pathways, including transforming growth factor beta (TGF-β1) and the TL1A/DR3 axis. Genetic susceptibility, notably variants in NOD2 and other fibrosis-related genes, contributes not only to disease risk but also to phenotype progression. Epigenetic mechanisms, particularly microRNAs such as the miR-29 and miR-200 families, further modulate fibrogenesis and represent promising non-invasive biomarkers. Additionally, intestinal dysbiosis and specific microbial signatures, including reduced short-chain fatty acid-producing bacteria and the presence of adherent-invasive Escherichia coli, play a critical role in promoting fibrotic pathways. Mesenteric adipose tissue, especially creeping fat, also contributes to fibrosis through immune and metabolic signaling. Emerging biomarkers related to collagen metabolism and advances in molecular profiling are improving early detection strategies. Novel therapeutic approaches targeting fibrogenic pathways, including anti-TL1A agents, show promising preliminary results. A deeper understanding of these mechanisms is essential to develop effective antifibrotic therapies and improve long-term outcomes in CD. Full article

Calycosin-7-O-β-D-glucoside (CG), a bioactive compound extracted from the traditional Chinese herb Astragalus (AR), exhibits diverse biological activities, including anti-oxidative and anti-inflammatory effects, and has shown protective properties in ischemia–reperfusion (I/R) injury. While previous studies have demonstrated that CG mitigates I/R injury primarily through its anti-oxidative and anti-inflammatory actions, its potential role in promoting neuroregeneration—a critical process for stroke recovery—remains unclear, and the underlying mechanisms have yet to be elucidated. In this study, an ischemic stroke model was established in rats via middle cerebral artery occlusion (MCAO). Seven days after CG treatment, cerebral infarct volume was assessed using triphenyltetrazolium chloride (TTC) staining, while neurological function was evaluated through behavioral tests. Nissl staining and Bielschowsky silver staining were employed to examine neuronal damage and axonal loss, and immunofluorescence was used to assess axonal regeneration. The expression of key proteins in the Rho/ROCK signaling pathway was analyzed by Western blotting (WB) and quantitative real-time PCR (qRT-PCR). CG treatment significantly reduced infarct volume, promoted axonal regeneration, improved neurological outcomes, and modulated the expression of RGMa, Rho, ROCK, and CRMP2. Collectively, these findings provide the first evidence that CG facilitates axonal regeneration and neurological recovery after cerebral ischemia, at least in part by inhibiting activation of the Rho/ROCK pathway, highlighting its potential as a therapeutic agent for ischemic stroke. Full article

Background: Asthma is a heterogeneous chronic airway disease characterized by inflammation, airflow obstruction, hyperresponsiveness, and remodeling. Severe eosinophilic asthma is driven by eosinophilic inflammation, which contributes to tissue damage, recurrent exacerbations, and progressive impairment of airway structure and function. Eosinophils play a central role through the release of cytokines, cytotoxic granule proteins, and extracellular traps, and their persistence in the airways is sustained by type 2 inflammatory pathways, particularly interleukin-5-mediated signaling. A better understanding of eosinophil biology has promoted the development of targeted therapies, including anti-interleukin-5/interleukin-5 receptor agents and biologics that indirectly modulate eosinophilic inflammation, such as anti-interleukin-4 receptor alpha and anti-thymic stromal lymphopoietin antibodies. Aim: This narrative review summarizes the immunopathology of eosinophilic asthma and links eosinophil biology to current and emerging pharmacological strategies. We discuss biologics that directly target the IL-5/IL-5 receptor axis, as well as agents that indirectly modulate eosinophilic inflammation, including IL-4 receptor alpha and TSLP blockade. We also review the clinical positioning of available biologics, focusing on blood eosinophils, FeNO, exacerbation history, oral corticosteroid exposure, lung function, type 2 comorbidities, treatment response, remission and switching. Conclusions: Overall, eosinophilic inflammation remains a central therapeutic target and a key component of precision medicine in severe asthma, but biologic selection should be individualized and reassessed through multidomain clinical outcomes. Full article

Lactoferrin is a naturally occurring bioactive glycoprotein that is part of the body’s innate immune system and has essential roles in iron metabolism, microbial defense, inflammation regulation, and tissue repair. It supports the natural regulation of iron bioavailability in skin and hair follicles, helping to reduce excess free-iron-driven oxidative stress while preserving levels of necessary iron for cellular functions. Lactoferrin promotes cell regeneration by increasing proliferation across in vitro systems, stimulating wound healing in scratch assays, and boosting matrix production in fibroblast models. Lactoferrin can also modulate inflammatory signaling involved in skin and hair physiology by providing balanced cytokine suppression, suggesting potential value in cosmetic or dermatological applications. Here, we present the first focused summary of lactoferrin’s role specifically in skin and hair biology, distinguished from prior reviews in systemic or multi-system broad health contexts. We link mechanistic insights with clinical and preclinical evidence and uniquely map molecular functions to dermatologic and trichologic outcomes. We also provide an overview of clinical skin studies that have explored lactoferrin as a supportive agent in conditions such as acne, and highlight that, despite mechanistic plausibility, there are no existing available reports of well-controlled human clinical trials leveraging lactoferrin for hair-focused outcomes. In summary, we propose lactoferrin as not just an anti-inflammatory molecule, but also as a microenvironment stabilizer, and particularly relevant for hair and skin support as an alternative to pharmacological interventions. By addressing both established and underexplored applications, this review provides a translational framework for clinical development and provides a comprehensive rationale behind leveraging lactoferrin for hair and skin epithelial health. Full article

A series of coumarin–amino acid hybrids of glycine, γ-aminobutyric acid, and L-glutamic acid was developed. These compounds were evaluated for their antioxidant and anti-inflammatory activities in vitro and for their drug-likeness in silico. Antioxidant activity was assessed in vitro using the AAPH-induced linoleic acid peroxidation assay. Soybean lipoxygenase and ovine cyclooxygenase 2 were used in vitro to test the inhibitory activity of the adducts. An in silico evaluation was performed using the open-access platforms Molinspiration, SwissADME, PreADMET, Molsoft, GLORYx, CypRules, and LiverTox Workspace. The synthesis of the compounds proceeded via a facile procedure through the corresponding acid in very good yields. The antioxidant activity of the compounds is shown to be highly dependent on the linkage used, with compound 15 presenting the highest activity (93% inhibition). The most active LOX inhibitor is compound 4 (IC₅₀ = 58 μM), while compounds 4 and 5 are the most potent COX-2 inhibitors (IC₅₀ = 55 μM for both). Compounds 4, 9, and 15 are depicted as pleiotropic molecules (compound 4: IC₅₀ for SLOX-1 = 58 μM and IC₅₀ for COX-2 = 55 μM; compound 9: IC₅₀ for COX-2 = 60 μM, and 59% antilipid peroxidation; compound 15: IC₅₀ for COX-2 = 70.5 μM, 93% antilipid peroxidation). An in silico evaluation showed favorable properties of the designed agents, which were quantified, with all the compounds showing a QED score higher than 0.5. The overall results highlight that compound 4 can be used as a lead molecule for the design of more potent agents with a pleiotropic profile. Full article

Pistacia lentiscus L. var. Chia is an endemic tree cultivated in the Southern part of Chios Greek Island. Chios mastiha, the aromatic resin secreted from this tree, has been used as traditional remedy since ancient times to cure many peptic system diseases and as a nutritional agent. Nowadays, Chios mastiha has been widely investigated for its biological activities and its chemical composition. A major part of Chios mastiha’s bioactive compounds are triterpenoids, which are proposed to interfere with glucocorticoid receptor (GR) signaling, acting as selective GR agonists. In this study a specific “neutral fraction” of Chios mastiha resin, a portion devoid of acidic triterpenoids, was investigated regarding its biological potential and chemical composition. The study aimed to determine if the neutral triterpenoids, the non-carboxylic ones, within this fraction drive Chios mastiha’s interference with GR signaling and whether it exhibits anti-inflammatory, apoptotic, and potential antilipidemic activities. The phytochemical characterization of this specific resin portion, applying ¹H NMR and HPLC-QTOF-MS/MS analysis, identified novel unidentified Chios mastiha’s phenolic components (apigenin, astragalin, diosmetin, flavidin, genistein), a complex mixture of fatty acids (palmitic, stearic, oleic), non-carboxylic triterpenoids (lupeol, β-amyrin, keto-oleanolic aldehyde), and a trace of terpenoids. Biological assessment of DEX-induced GR transcriptional activation revealed that neutral triterpenoid fractions only minimally contribute to GR transcriptional activation while positively regulating GR and its target, phosphoenolpyruvate carboxykinase (PEPCK), protein levels. Additionally, negative regulation of the peroxisome proliferator-activated receptor alpha (PPARα) protein levels as well as inhibition of the TNFα-induced NF-κΒ activity and reduction in the p65 subunit of NF-κΒ protein levels, were observed, indicating potential antilipidemic and anti-inflammatory Chios mastiha’s neutral fraction activities, which were attributed to its composition in triterpenoids, fatty acids, and novel phenolic compounds. Moreover, mitochondrial-dependent induction of apoptosis accompanied by reduction in cell viability was observed in lupeol, β-amyrin, and fatty acids-enriched fractions. The plethora of bioactive compounds associated with a variety of Chios mastiha’s neutral fraction render Chios mastiha a valuable food additive and nutritional agent. Full article

Background/Objectives: Chronic inflammatory skin diseases are frequently associated with pruritus, in which the neurokinin-1 receptor (NK₁R) and its ligand substance P (SP) play a central role. The development of compounds combining anti-inflammatory and antipruritic effects represents a promising therapeutic strategy. This study aims to identify fiscalin B derivatives as anti-inflammatory agents with high affinity to NK₁R using an integrated in silico and in vitro approach. Methods: A library of fiscalin B derivatives was screened through molecular docking against NK₁R to identify high-affinity ligands. Selected compounds were further evaluated using in silico ADMET and toxicity predictions. In vitro assays were conducted in HaCaT keratinocytes, RAW264.7 macrophages, and NIH/3T3 fibroblasts to assess cytotoxicity, nitric oxide production, inflammatory proteins expression, and cell migration. Results: Docking studies identified several derivatives with predicted binding affinities comparable to or exceeding those of aprepitant, a well-established NK₁R antagonist. Several compounds, particularly 2, 3, 4, 6, and 7, reduced lipopolysaccharide-induced nitric oxide production to 41–51% without relevant cytotoxicity. This effect was associated with reduced iNOS protein levels, suggesting modulation of inflammatory pathways rather than direct nitric oxide scavenging. Most compounds showed positive safety profiles, although in silico analysis indicated limited biodegradability and potential aquatic toxicity. Conclusions: The fiscalin B derivatives, 2, 3, and 4, demonstrate potential as anti-inflammatory agents, in vitro, and as NK₁R high affinity ligands, in silico. These findings support their potential as lead compounds for topical therapies for inflammatory skin disorders associated with pruritus, although further optimization and validation are required. Full article