Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, driven by immune dysregulation, oxidative stress, and the release of pro-inflammatory cytokines. Histamine, an important mediator in gut inflammation, has immunomodulatory properties. Ebastine, a second-generation histamine H1-receptor antagonist, is primarily used for allergic conditions, but its potential role in managing IBD has not been fully explored. This study aimed to evaluate whether ebastine could prevent colitis induced by dextran sodium sulfate (DSS) in mice. The severity of the condition was assessed using the disease activity index (DAI), body weight loss, stool consistency, and rectal hemorrhage. Immune modulation was investigated by measuring serum IgE levels and inflammatory biomarkers like C-reactive protein (CRP). The study also examined the impact of ebastine on oxidative stress markers and pro-inflammatory cytokines (TNF-α, IL-6), alongside histopathological analysis of colon tissue. Swiss albino mice were induced with experimental colitis using 3
Cycas revoluta Thunb. has traditionally been used for the management of gastrointestinal and inflammatory disorders, but its bioactive constituents and anti-inflammatory potential remain insufficiently characterized. This study aimed to optimize the extraction of phenolic-rich compounds from C. revoluta leaves and evaluate the anti-inflammatory and coloprotective effects of the optimized extract against experimental ulcerative colitis (UC). Four extraction techniques, namely Soxhlet extraction, maceration, ultrasound-assisted extraction (UAE), and microwave-assisted extraction (MAE), were compared based on extraction yield, total phenolic content (TPC), total flavonoid content (TFC), antioxidant, and antibacterial activities. The most effective method was subsequently optimized using response surface methodology (RSM) using a Box–Behnken design (BBD), followed by phytochemical investigation and biological evaluation in rats with acetic acid-induced UC. Maceration showed the best performance, yielding the highest TPC (44.21 mg GAE g−1 DM), TFC (33.77 mg RE g−1 DM), DPPH inhibition (82.2
Osteoarthritis (OA) is a multifactorial joint disorder characterized by inflammation, oxidative stress, and progressive cartilage degeneration, for which conventional therapeutic agents remain limited by low bioavailability and systemic side effects. This study aims to integrate in silico guided and experimental nanoparticle-based drug formulations and in vivo analysis targeting the inflammatory genes, proteins, and oxidative markers in OA therapy. In silico screening was conducted on ligands based on SwissSimilarity and led to the identification of TNF-α inhibitors. High binding affinity and stability of the complex were verified by Docking studies (AutoDock Vina) and molecular dynamics simulations (Desmond), 100 ns. THA was produced. SLNs with Diacerein (DC-SLNs) were prepared and entrapped into thermosensitive in situ gels (ISG) that were made of THA, poloxamer 407 and poloxamer 188. The formulations were assessed physically and in vitro release dynamics. The efficacy of in vivo drug formulation was determined by osteoarthritis rat model with knee diameter, oxidative and inflammatory markers. Swiss-similarity screening with Rhein as a reference ligand identified eight structurally similar compounds in the DrugBank database, including Diacerein, Rheinanthrone, Salsalate, and others, with high similarity scores (> 0.7); DC showed the strongest TNF-α binding (− 10.7 kJ/mol). The complex stability was proved by MD simulations (RMSD 2.6 A). In both gels, gelation was appropriate, injectability was excellent, and non-Fickian release occurred. Thermal studies, PXRD, and SEM showed lower crystallinity and a porous structure. Both formulations yielded significant reductions in joint swelling, pro-inflammatory cytokines (TNF-α, IL-6, NF-κB), improved antioxidant activity, and reduced inflammatory and oxidative mediators associated with cartilage degradation, while the DC-SLN@THA-ISG has better therapeutic efficacy than DC@THA-ISG. In silico in vivo studies prove the efficacy of DC-SLN@THA-ISG as a biocompatible and sustained intra-articular formulation in managing osteoarthritis.
Chronic low-grade inflammation and oxidative stress are hallmarks of metabolic disorders. A naturally occurring polyphenol, resveratrol (RSV), has shown promise in modulating these pathways, however clinical evidence is mixed. To systematically review and perform a dose–response meta-analysis of randomized controlled trials (RCTs) to assess the effects of RSV supplementation on inflammatory and oxidative stress biomarkers in patients with these disorders. A systematic search up to August 2026 following PRISMA guidelines was conducted to identify RCTs that examined the effect of RSV on inflammatory (including C-reactive protein (CRP), Tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6)) and oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC)) biomarkers in populations with metabolic disorders. Random effects models were used to combine the data. Dose–response relationships were evaluated using linear and non-linear modelling. Trial sequential analysis (TSA) was performed to adjust for repetitive testing, calculate the required information size (RIS), and assess the robustness of the cumulative evidence. Meta-analysis of 25 RCTs for CRP showed a statistically significant reduction (SMD = −0.18, 95
Current disease-modifying therapies for multiple sclerosis (MS) primarily target adaptive immunity but often fail to halt neurodegeneration or promote myelin repair. Leukotriene pathway inhibitors, established in the management of asthma, possess anti-inflammatory and potentially neuroprotective properties. Following the PRISMA 2020 recommendations, a systematic search was conducted in PubMed, Web of Science, and Scopus. Eligible studies included preclinical investigations of leukotriene inhibitors in MS animal models and risk of bias was assessed using SYRCLE’s risk of bias tool for animal studies. Five studies met the inclusion criteria, reported that inhibition of leukotriene B4 (LTB4) or cysteinyl leukotriene receptor 1 (CysLT1) attenuated clinical severity in experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced demyelination models. Mechanistically, the included preclinical studies suggest that leukotriene inhibitors may influence several pathways potentially relevant to MS pathophysiology, including T helper 17 (Th17) cell differentiation, M1-like microglial polarization, and oligodendrocyte precursor cell (OPC) differentiation. In addition, targeted central nervous system (CNS) delivery using engineered exosomes appeared to enhance the observed remyelination effects. Leukotriene inhibition may exert pleiotropic effects across both peripheral immune responses and the CNS microenvironment. Although these mechanistic observations provide biological plausibility for further investigation of these agents as potential repurposed therapies for MS, particularly in the context of remyelination and neuroinflammation, they remain based on preclinical evidence and should therefore be considered hypothesis-generating. Well-designed clinical studies are required to determine whether these experimental effects translate into clinically meaningful therapeutic benefits in patients with MS.
