Search Results (752)

Inflammation plays a central role in the pathogenesis of numerous diseases through the excessive production of nitric oxide (NO), prostaglandins, and pro-inflammatory cytokines. Although bromophenols from marine algae and various phenolic compounds exhibit strong anti-inflammatory activity, the biological properties of brominated vanillin derivatives remain largely unexplored. This study aimed to investigate the anti-inflammatory effects of 2-bromo-5-hydroxy-4-methoxybenzaldehyde (2B5H4M), a brominated vanillin derivative structurally similar to marine bromophenols, in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. 2B5H4M significantly reduced LPS-induced NO and PGE₂ production by suppressing the protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). It also downregulated the expression of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Mechanistically, 2B5H4M inhibited the phosphorylation and degradation of IκB-α, thereby preventing NF-κB nuclear translocation, and reduced the phosphorylation of ERK and JNK. These findings demonstrate that 2B5H4M exerts potent anti-inflammatory effects by simultaneously blocking NF-κB and MAPK signaling pathways. Although not algae-derived, the structural resemblance of 2B5H4M to marine bromophenols highlights its potential as a marine-inspired reference compound. This work suggests that 2B5H4M may serve as a promising lead scaffold for developing new phenolic anti-inflammatory agents and provides a foundation for future mechanistic and in vivo studies. Full article

Bovine viral diarrhea virus (BVDV) causes severe mucosal inflammation in cattle, and effective treatment options remain limited. Dysregulated activation of the NLRP3 inflammasome, driven by NF-κB and STAT3 signaling, may exacerbate disease pathogenesis, highlighting this axis as a potential therapeutic target. Although traditional Chinese medicine has shown promise in antiviral and anti-inflammatory applications, it remains unclear whether it can inhibit BVDV replication via the NF-κB/STAT3-NLRP3 pathway. The present study aimed to clarify the inhibitory effect of luteolin on bovine viral diarrhea virus (BVDV) replication, and to elucidate its underlying mechanisms from two perspectives: interference with viral internalization and replication processes, as well as regulation of the NF-κB/STAT3-NLRP3 inflammasome pathway. Collectively, this work intended to provide experimental evidence and theoretical support for the development of luteolin as a natural anti-BVDV agent. To this end, BVDV-infected MDBK cells were treated with gradient concentrations of luteolin, followed by quantification of viral load using qRT-PCR and Western blot assays. Meanwhile, the activation status of the NF-κB/STAT3-NLRP3 signaling pathway was evaluated via immunofluorescence staining and luciferase reporter gene assays. Our results demonstrate that luteolin exhibits potent dual antiviral activity against cytopathic BVDV-1m in MDBK (Madin-Darby Bovine Kidney) cells, effectively suppressing both viral replication and inflammatory responses. At non-cytotoxic concentrations, luteolin specifically inhibited the internalization and replication stages of the viral lifecycle, accompanied by reduced NS5B polymerase activity. Importantly, luteolin disrupted the NF-κB/STAT3-NLRP3 axis by suppressing phosphorylation of p65 (Ser536) and STAT3 (Ser727), downregulating NLRP3 and pro-caspase-1 expression, and inhibiting caspase-1 cleavage (p20) as well as maturation of IL-1β and IL-18. Consequently, it attenuated the overexpression of TNF-α and IL-8. To our knowledge, this is the first report of a single compound simultaneously targeting multiple stages of the BVDV lifecycle and counteracting NLRP3-mediated immunopathology, offering a strategic basis for developing flavonoid-based therapies against Flavivirus infections. Full article

The genus Plantago (Plantaginaceae) is widely distributed worldwide. The Plantago species are used in traditional medicine as wound healers, anti-inflammatory agents, antipyretics, and analgesics. This study aimed to investigate the phytochemical composition from the aerial parts of Plantago indica L. and to evaluate its biological activities. Isolation studies and in vitro investigations were conducted on an aqueous phase of 80% EtOH extract of Plantago indica. In addition, in vivo studies were carried out using the MeOH, 80% EtOH, and water extracts. Plantarenaloside (1), 3-oxo-α-ionol β-glucoside (2), martynoside (3), acteoside (4), feruloyl gardoside (5), and ursolic acid (6) were isolated from the extract. The structures of the compounds were elucidated using 1D- and 2D-NMR and ESI-MS analyses. The extract, fractions, and pure compounds were tested in vitro for cytotoxicity (MTT), anti-inflammatory activity (NO, IL-6, and TNF-α production), wound healing (scratch test), and antioxidant capacity (DPPH, ABTS, SO). Feruloyl gardoside (20.11–58.27%) significantly reduced NO levels at concentrations of 25–100 µM. It significantly reduced IL-6 levels (40.17%) at 100 µM. Additionally, the in vivo anti-inflammatory (acetic acid-induced vascular permeability) and wound healing (incision and excision models) effects of the extracts were investigated. The findings suggest that P. indica may be considered to be a potential therapeutic option for managing inflammation and for promoting wound healing. Full article

Background/Objectives: Osteoarthritis (OA) is a multifactorial degenerative joint disease characterized by synovial inflammation, oxidative stress, and progressive cartilage degeneration. This study investigated whether intra-articular N-acetylcysteine (NAC) attenuates synovial inflammation and oxidative stress and whether these effects translate into structural cartilage protection. Methods: OA was induced in rats by anterior cruciate ligament transection (ACLT). NAC (5 mg/50 µL) was administered intra-articularly once weekly for three weeks post-ACLT. Inflammatory cytokines (IL-1β, IL-6, TNF-α), oxidative stress markers (iNOS, TAS, TOS, OSI), and cartilage degradation markers (MMP-13, COMP, CTX-II) were quantified in synovial fluid and cartilage homogenates using ELISA. Cartilage integrity was evaluated histologically using the modified Mankin scoring system. Results: Compared with controls, NAC significantly reduced synovial IL-1β, IL-6, TNF-α, MMP-13, and iNOS levels and improved the synovial redox profile by increasing TAS and reducing TOS and OSI (all p < 0.05). In contrast, NAC did not significantly alter cartilage homogenate levels of inflammatory cytokines, oxidative stress indices, or degradation markers (COMP, CTX-II, MMP-13). Histological analysis demonstrated persistent cartilage fissuring, hypocellularity, and proteoglycan loss in both groups (p > 0.05). Conclusions: Intra-articular NAC exerts potent anti-inflammatory and antioxidative effects within the synovial compartment but fails to prevent cartilage degeneration in the ACLT model. These findings indicate a compartment-specific therapeutic profile, suggesting that NAC may function as a symptom-modifying agent in synovitis-dominant OA rather than a structure-modifying therapy. Future studies should focus on optimized delivery systems or combination strategies targeting cartilage and subchondral bone to achieve disease modification. Full article

Microalgae have garnered increasing attention as promising sources of diverse natural anti-inflammatory compounds, including carotenoids, phenolics, and unsaturated fatty acids. In this study, we aimed to examine the anti-inflammatory properties of the methanol extract of Nannochloropsis sp. G1-5 (NG15), a strain of marine microalgae isolated from the southern West Sea of the Republic of Korea. Pigment and metabolite analyses revealed that the extract contained various carotenoids and polyunsaturated fatty acids alongside significant quantities of phenolic and flavonoid compounds, which are known to have anti-inflammatory activities. Cytotoxicity assays confirmed that the extract was non-toxic to RAW 264.7 macrophage cells at concentrations up to 1 mg/mL. Upon lipopolysaccharide (LPS) stimulation of the macrophage cells, the NG15 extract significantly inhibited nitric oxide (NO) production in a dose-dependent manner up to 81%. In addition, the NG15 extract reduced the expression of iNOS, COX-2, TNF-α, and IL-6 in the LPS-stimulated cells. These findings suggest that NG15 methanol extract exerts anti-inflammatory effects primarily through the suppression of NO generation without inducing cytotoxicity. Overall, these results underscore NG15 as a promising natural resource for the development of non-toxic and effective anti-inflammatory agents with potential applications in the biomedical and cosmeceutical industries. Full article

Background/Objectives: Acetaminophen (paracetamol or APAP) overdose is a major cause of acute liver injury mediated by oxidative stress, inflammation, and hepatocellular necrosis. The present study investigates the in vivo hepatoprotective potential of morin (M), lignin nanoparticles (LN), and morin-encapsulated lignin nanoparticles (LMN) against APAP-induced hepatotoxicity in mice. The specific goal was to determine whether LMN could strengthen hepatic antioxidant and anti-inflammatory defenses prior to toxic insult, which aligns with a prophylactic model rather than a post-injury clinical rescue approach. This study was guided by the primary hypothesis that LMN pretreatment would markedly reduce APAP-induced hepatic injury. Methods: Experimental groups included control, APAP, M, LN, LMN, M+APAP, LN+APAP, and LMN+APAP treatments. Serum hepatic biomarkers, oxidative stress parameters, and inflammatory cytokines were analyzed to assess protective responses. Results: APAP exposure markedly elevated aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels, indicating severe hepatic dysfunction, accompanied by increased lipid peroxidation and pro-inflammatory cytokine production. LMN+APAP treatment significantly restored hepatic enzyme levels to approximately normal values and suppressed malondialdehyde (MDA) formation, while enhancing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. LMN also downregulated interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin 1β (IL-1β), while upregulating interleukin 10 (IL-10), suggesting effective attenuation of inflammatory signaling. Correlation analyses demonstrated positive interactions between MDA, cytokines, and hepatic enzymes, whereas antioxidant enzyme levels were inversely correlated with liver injury markers. Histopathological analysis revealed that treatment with LMN enhanced hepatoprotection, demonstrating predominantly mild, reversible lesions and suggesting a synergistic antioxidant and immunomodulatory effect. Conclusions: It could be concluded that LMN provided superior hepatoprotection compared to M or LN. These findings establish LMN as a promising bio-based nanotherapeutic agent for mitigating drug-induced hepatotoxicity through coordinated antioxidant and anti-inflammatory mechanisms. Full article

Objective: Acteoside (ACT) has different pharmacological properties such as antioxidant, hepatoprotective and anti-inflammatory effects. Impaired mitophagy has been recognized as an important pathogenic factor in metabolic dysfunction-associated steatotic liver disease (MASLD). Nevertheless, the possible therapeutic role of ACT in MASLD and the exact effect of ACT on mitophagy regulation are not explored. This study aims to elucidate the therapeutic efficacy of ACT in a high-fat and high-sugar (HFHS) diet-induced mouse model of MASLD and to determine whether its effects are related to the activation of PINK1/Parkin-related mitophagy markers. Methods: C57BL/6J mice were randomly allocated to control, model, rosuvastatin (RSF, 3 mg/kg), and ACT (30, 60, and 120 mg/kg) groups. Following a 14-week continuous intervention, biochemical parameters, liver histology, and mitophagy-related markers were assessed. Results: ACT administration significantly improved serum lipid profiles, liver function and insulin resistance, marked by reduced levels of MDA, IL-6, TNF-α, IL-1β, LDL-C, TC, TG, AST, ALT, HOMA-IR (p < 0.05), while increasing HDL-C and enhancing hepatic GSH-Px and SOD activities (p < 0.05). Histological examination revealed a notable attenuation of hepatic steatosis and lipid accumulation. At the molecular level, ACT promoted mitophagy activation, as indicated by upregulated PINK1, LC3II/I, and Parkin expression and downregulated P62 and p-P62. Electron microscopy further validated the restoration of mitochondrial morphology and reduction in lipid droplets. Conclusions: These results demonstrate that ACT ameliorates MASLD progression by improving metabolic homeostasis, reducing inflammation and oxidative stress, and alleviating PINK1/Parkin-related mitophagy impairment to restore mitophagy homeostasis. Our study highlights the potential of ACT as a new therapeutic agent for MASLD. Full article

Cancer cachexia (CC) is a multifactorial, multi-organ syndrome characterized by systemic inflammation, metabolic dysregulation, anorexia, and progressive depletion of skeletal muscle and adipose tissue. Despite its high prevalence among patients with advanced malignancies, effective therapeutic options remain limited. Recent studies have elucidated the molecular underpinnings of CC and the therapeutic potential of natural herbs, highlighting the involvement of central nervous system regulation, adipose tissue, immune responses, gut microbiota, skeletal muscle, and disruptions in anabolic–catabolic signaling pathways such as mTOR, UPS, NF-κB, and STAT3. Persistent inflammation induces E3 ubiquitin ligases (Atrogin-1/MuRF-1) through cytokines including IL-6 and TNF-α, thereby impairing muscle homeostasis, while suppression of anabolic cascades such as IGF-1/mTOR further aggravates muscle atrophy. The limited efficacy and adverse effects of synthetic agents like megestrol acetate underscore the value of herbal therapies as safer adjunctive strategies. Botanicals such as Coicis Semen, Scutellaria baicalensis, and Astragalus demonstrate anti-inflammatory and muscle-preserving activities by modulating NF-κB, IL-6, and oxidative stress signaling. Numerous investigations indicate that these herbs downregulate MuRF-1 and Atrogin-1 expression, enhance appetite, and attenuate muscle loss, though they exhibit minimal influence on tumor suppression. While promising, current evidence remains largely preclinical and mechanistic validation is incomplete. This review consolidates contemporary insights into CC pathogenesis and the bioactivity of herbal interventions, highlighting the need for translational research to bridge preclinical findings with clinical applicability. Full article

Background: Recently, data have been published about the inhibitory effect at low nanomolar concentrations on the TRPV1 ion channel for a new indole derivative named SV-1010. This molecule has also been shown to have a strong analgesic effect in mice and rats. Since the biological target of SV-1010 is the TRPV1 ion channel, which plays an active role in inflammation, we conducted a series of animal tests to evaluate its potential as an anti-inflammatory agent. Methods: Nine different inflammatory agents were used to assess acute inflammation, and diclofenac was chosen as a positive control. Additionally SV-1010 effects in chronic proliferative and immunogenic inflammation models were also measured. Results: SV-1010 demonstrated a significant effect in most inflammatory tests, often surpassing that of diclofenac, and showed comparable efficacy to several other recognized anti-inflammatory drugs under certain conditions. The level of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, exceeded after LPS administration was normalized to the non-LPS control group level by a dose of 0.1 mg/kg of SV-1010, and the effect was comparable to that of diclofenac at a dose of 12.5 mg/kg. The estimation by qPCR of the content of two enzymes, COX-2 and iNOS, which were increased by 10.8- and 19.4-fold, respectively, after LPS induction showed different molecular targets being utilized, manifested in the normalization of COX-2 content only after diclofenac treatment, and iNOS content only after SV-1010 treatment. Conclusions: Due to the simplicity of synthesis and low effective dose for mammal treatment, this compound can be interesting for a practice. Full article

Obesity is a major contributor to kidney injury, in part through circadian rhythms disruption and oxidative stress. Melatonin, a circadian clock regulator, has been proposed as a protective agent against metabolic and renal complications. We investigated the effects of chronic melatonin supplementation on kidney injury and circadian regulation in a rat obesity model. We hypothesized that melatonin administration ameliorates kidney injury induced by a high-calorie diet. Male Wistar rats were fed a normal or hypercaloric diet for six weeks, followed by seven weeks of vehicle or melatonin treatment (30 mg/kg/day in drinking water); biometric parameters and renal injury were assessed. Obese rats exhibited increased visceral adiposity, elevated resistin, renal hypertrophy, fibrosis, tubular degeneration, and glomerular injury, accompanied by higher KIM-1 levels. Melatonin attenuated renal fibrosis, reduced KIM-1, TGFβ, and TNFR1 levels, improved proximal tubule and glomerular damage, and lowered adipose TNF-α levels in the obese groups. In lean controls, melatonin increased nuclear BMAL1 levels, while in obese rats this effect was blunted; of note, BMAL1 accumulated in distal tubular cytoplasm in both melatonin-treated groups. These findings suggest that melatonin mitigates obesity-induced renal pathology through anti-fibrotic inflammation-related mechanisms, while also revealing a novel link between circadian disruption and kidney injury. Our results support melatonin as a therapeutic agent for obesity-related renal disease. Full article

This article explores a rare and diagnostically challenging form of Crohn’s disease, known as Oral Crohn’s Disease (OCD), in which the condition is confined to the oral cavity without gastrointestinal involvement. Additionally, Crohn’s disease is typically associated with digestive manifestations, and oral lesions may occasionally represent the first- or even the sole- signs of the disease, making diagnosis difficult due to their non-specific presentation. We report the case of a 22-year-old presenting woman suffering from chronic painful gingivitis and macrocheilitis, in the absence of gastrointestinal symptoms. Despite multiple topical treatments and an initial non-specific histopathological report, a multidisciplinary case discussion and re-evaluation of biopsies led to the diagnosis of OCD. Comprehensive gastrointestinal assessments revealed no intestinal involvement. Owing to the persistence of symptoms and resistance to topical therapies, the patient was subsequently treated with an anti–TNFα (Tumor Necrosis Factor alpha) biologic agent. To contextualize this case, we conducted a literature review and identified six similar cases published between 2000 and 2025. Reported patients presenting with symptoms such as lip swelling, cheilitis, mucosal ulcerations, and gingivitis. Histopathological findings consistently demonstrate non-caseating granulomas and inflammatory cell infiltration. Most cases responded favorably to corticosteroids, while some required systemic or biologic therapy. The article highlights that OCD remains underrecognized due to its variable clinical presentation and absence of gastrointestinal manifestations. It emphasizes the importance of integrating clinical, histological, and exclusion-based diagnostic criteria and advocates for a multidisciplinary approach involving dental surgeons, dermatologists, pathologists, and gastroenterologists. Early recognition and long-term monitoring are essential, as gastrointestinal involvement may develop years after the onset of oral symptoms. Full article

Background: Drug-induced cardiotoxicity is a primary concern in clinical practice, especially in the context of oxidative stress induced by anti-cancer, antiviral, and antidiabetic drugs. Several strategies are devised to limit cardiotoxicity, which are supportive and provide symptomatic relief. This highlights the need to develop cardioprotective agents that circumvent the oxidative stress. Bassia indica is a cardiotonic plant with antioxidant properties traditionally used in Africa, South Asia, and China. We investigated its cardioprotective effects against doxorubicin-induced cardiotoxicity (DIC). Methods: B. indica extract (BiE) was analyzed by GC-MS and HPLC. Several antioxidant assays, including DPPH, FRAP, CUPRAC, NO, and H₂O₂ scavenging, were performed. In vivo attenuation of DIC was assessed in a rat model. Results: BiE contained several bioactive flavonoids, including 2-methoxy-4-vinylphenol, ferulic acid, gallic acid, kaempferol, and coumaric acid. Antioxidant assays demonstrated potent free-radical scavenging and antioxidant activity of BiE, providing mechanistic evidence for its in vivo amelioration of DIC. BiE treatment reduced myocardial oxidative stress by increasing endogenous antioxidant levels (p < 0.01), including SOD, CAT, and GSH. It upregulated Nrf2 and lowered Keap1 levels. This was also reflected in the restoration of cardiac tissue architecture and modulation of inflammatory markers, including IL-1β and TNF-α (p < 0.01). Cardiac tissue biomarkers were also improved. Conclusions: These findings conclude that BiE exerts cardiac protection by reducing oxidative stress and inflammation through modulation of the Keap1/Nrf2 pathway and decreasing the expression of IL-1β and TNF-α. Full article

Background/Objectives: Plaque psoriasis is a chronic immune-mediated inflammatory disease affecting approximately 3% of the global population and resulting in a significant deterioration in quality of life. Systemic therapy with monoclonal antibodies (mAbs) targeting TNF-α, IL-23, and IL-17 improves clinical outcomes and patients’ quality of life. Treatment strategies commonly include different mAbs and different sequencing approaches between agents, which are well-established in clinical practice. In contrast, evidence supporting the switch from intravenous to subcutaneous administration of the same mAb remains limited. Herein, we report data from a retrospective case series of patients with plaque psoriasis treated with intravenous infliximab (IV-IFX; Anti TNF-α) and transitioned to subcutaneous infliximab (SC-IFX) to compare clinical and patient-reported outcomes across routes. Methods: A total of 11 plaque psoriasis patients were retrospectively analyzed. The scores of the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Physician Global Assessment (PGA) were assessed during IV-IFX and after switching to SC-IFX. To evaluate patients’ satisfaction, the Score of Treatment Satisfaction Questionnaire Medication-9 (TSQM-9) was evaluated. Both Student’s t-test and ANOVA were used to assess statistically significant differences between the two routes of administration (p < 0.05). Results: Scores for PASI, DLQI, and PGA were lower with SC-IFX compared with IV-IFX, indicating improved disease control and quality of life after the switch. PASI and DLQI improved in 81% and 100% of patients treated with SC-IFX, respectively. TSQM-9 total scores increased significantly by 24% (p < 0.001). In particular, the questions addressing the “convenience” of treatment revealed a marked advantage for the SC-IFX formulation (p < 0.001). No treatment-emergent adverse events were registered. Conclusions: In this retrospective case series, switching from IV-IFX to SC-IFX appeared to be safe and to maintain or improve clinical response and enhanced treatment satisfaction. These findings highlight the potential of SC-IFX as a viable maintenance option for patients with plaque psoriasis previously treated with IV-IFX. Full article

Skin is constantly exposed to UV radiation. While topical sunscreens are the main preventative measure, oral photoprotective agents are emerging as promising systemic adjuncts, offering uniform, continuous protection. This study presents the results of two clinical trials designed to evaluate the efficacy of supplementation with a standardized coriander (Coriandrum sativum L.) seed oil (CSO) in mitigating UV-induced skin damage, in comparison with a placebo. The first trial investigated the effects of CSO supplementation on women with reactive skin, assessing UVA+B-induced skin erythema and tumor necrosis factor-alpha (TNF-α) release. The second trial included women of all skin types and, in addition to the outcomes mentioned above, examined UVA-induced lipoperoxidation. Measurements were taken before and after 56 days of supplementation. CSO supplementation led to a significant reduction in UV-induced skin erythema and associated TNF-α levels in both cohorts, with decreases of 11.8% and 24.1% in the reactive skin group and 18.1% and 18.7% in the cohort with all skin types, respectively. In women of all skin types, UV-induced skin lipoperoxidation was reduced by 31.9% at 4 h and by 69.9% at 24 h post-exposure. To the best of our knowledge, this is the first study reporting the photoprotective efficacy of CSO. This finding is attributed to CSO’s high petroselinic acid content and its known anti-inflammatory properties. Full article

Gintonin-enriched fraction (GEF), a bioactive glycolipoprotein derived from Panax ginseng is known for its potential as a natural anti-inflammatory agent. Keratinocytes are closely related to the development and progression of various inflammatory skin conditions. However, the effect of GEF on inflammation-related responses in keratinocytes remains unclear. This study aimed to investigate whether GEF modulates key inflammatory responses in keratinocytes stimulated by tumor necrosis factor (TNF)-α. The effect of GEF on biological activities in TNF-α-stimulated keratinocytes (HaCaT cells) was evaluated using water-soluble tetrazolium salt, enzyme-linked immunosorbent, immunostaining, and immunoblotting assays. In TNF-α-stimulated HaCaT cells, GEF attenuated reactive oxygen species production, nitric oxide release, and inducible nitric oxide synthase expression. Moreover, GEF reduced the release of interleukin (IL)-6 and RANTES, while increasing the release of IL-10 in TNF-α-exposed HaCaT cells. Additionally, GEF treatment resulted in reduced cyclooxygenase-2 expression and prostaglandin E₂ release and inhibited TNF-α-induced translocation of nuclear factor-κB in HaCaT cells. Furthermore, TNF-α and IL-6 levels in ultraviolet B-irradiated HaCaT cells were reduced by GEF treatment. These findings indicated that GEF exerts anti-inflammatory effects on keratinocytes. This study provides a basis for the development of novel therapeutic approaches for the prevention and treatment of inflammatory skin disorders. Full article