Inflammopharmacology最新文献

Epilepsy is a neurological disease that significantly reduces the quality of life in diagnosed individuals. Given the imbalanced release of synaptic energy in the brain, seizures are the main hallmarks of epilepsy disorder. Conventional treatments often fall short in managing symptoms and preventing seizure recurrence. Curcumin has shown potential in seizure management due to its anti-inflammatory, antioxidant, anti-apoptosis, and neuroprotective properties. To gather latest evidence on effects of curcumin in treatment and prevention of seizures, focusing on its mechanisms of action and therapeutic potentials. Clinical, in vivo, and in vitro original studies have been gathered up to August 2024 from valid motor engines including PubMed, Google Scholar, Cochrane Library, and ScienceDirect. Curcumin significantly decreases pro-inflammatory cytokines (IL-6, IL-1β, MCP, TNF-α), while simultaneously increasing anti-inflammatory cytokines (IL-10). It suppresses expression of inflammatory genes and signaling pathways such as COX-2 and NLRP3. Its antioxidant effects are evidenced by the elevation of SOD, CAT, GPx, and GSH, along with reduction of oxidative stress markers (NO, MDA, iNOS, MLK, RIP-1, GFAP). Diminished caspase-3 levels and increased CA1 neuron survival ensure its anti-apoptotic properties. Additionally, curcumin regulates pivotal pathophysiological pathways including AP-1, JNK, c-fos, and c-jun. These actions collectively lead to a reduction in seizure severity, duration, and frequency, with increased seizure latency. Curcumin demonstrated significant therapeutic properties in the management of seizures through its anti-inflammatory, antioxidant, and anti-apoptotic effects. However, its clinical application is limited by bioavailability issues, necessitating further research to optimize delivery methods and confirm efficacy and safety through extensive clinical trials.

Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by macrophage activation and pro-inflammatory signaling, particularly via TNF-α and NF-κB pathways. Current therapies, including methotrexate and biologic agents, provide clinical benefits but are limited by systemic toxicity, high costs, and treatment resistance. Here, we report the development of sodium alginate (SA)-encapsulated nanoparticles incorporating Colchicum micranthum (CM) and Colchicum chalcedonicum (CC) extracts as a novel therapeutic approach for RA. Phytochemical profiling revealed distinct polyphenolic signatures in CM and CC, with CC exhibiting superior flavonoid content and antioxidant activity. Nanoparticles fabricated via ultrasonic homogenization displayed uniform nanoscale morphology (55-130 nm), enhanced thermal stability, and strong polymer-phenolic interactions, as confirmed by FTIR, DSC, TGA, and FEGSEM analyses. In THP-1 macrophages, free extracts exhibited dose- and time-dependent cytotoxicity, whereas encapsulated forms (SA/CM, SA/CC) improved cell viability and minimized toxicity. Upon LPS stimulation, SA/CC significantly suppressed TNF-α and NF-κB expression while restoring metabolic activity, outperforming both free extracts and SA/CM. These findings demonstrate that alginate encapsulation not only enhances the safety and bioactivity of Colchicum-derived compounds but also enables targeted modulation of inflammatory pathways central to RA pathogenesis. By combining the anti-inflammatory properties of plant-derived bioactives with the precision of nanodelivery, SA/CC nanoparticles represent a promising, cost-effective alternative to conventional DMARDs and biologics, warranting further preclinical and clinical evaluation.

Background and aim: Autoimmune blistering diseases (AIBDs), including pemphigus diseases, pemphigoid diseases, linear immunoglobulin A (IgA) bullous dermatosis (LABD), epidermolysis bullosa acquisita (EBA), and dermatitis herpetiformis (DH), are a group of diseases clinically characterized by erosions and blisters that involve the skin and mucosa. Tumor necrosis factor-alpha (TNF-α), a key inflammatory cytokine, plays a critical role in their pathogenesis. TNF-α inhibitors are used for their immunomodulatory effects but may also induce paradoxical autoimmune blistering. This systematic review aimed to synthesize current evidence on therapeutic and paradoxical effects of TNF-α inhibitors in these diseases.

Method: A systematic search of PubMed, Scopus, and Embase was conducted up to March 7th, 2025, following PRISMA guidelines. Studies eligible for inclusion were original human research articles in English reporting therapeutic or paradoxical effects of TNF-α inhibitors, including infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab, on autoimmune bullous diseases. Risk of bias was evaluated using the NIH and Murad et al. assessment tools.

Results: A total of 35 studies with 68 patients were included in the treatment application group and 29 studies with 31 subjects were included in the paradoxical reaction group. Infliximab was most frequently associated with favorable outcomes in pemphigus vulgaris (PV), bullous pemphigoid (BP), and EBA, with multiple reports of sustained remission. Etanercept showed partial to complete responses in some cases of PV and BP; however, it was associated with paradoxical induction of BP in several patients. Adalimumab demonstrated therapeutic efficacy in PV and MMP, yet was the most common agent implicated in paradoxical BP and LABD. Paradoxical effects were most often observed in patients treated for non-dermatologic conditions such as rheumatoid arthritis or Crohn's disease.

Conclusion: TNF-α inhibitors, particularly infliximab, show therapeutic promise in refractory AIBDs. However, their potential to paradoxically induce blistering diseases, especially with adalimumab and etanercept, necessitates careful patient selection, close monitoring, and individualized risk-benefit assessment.

Ardisiacrispin B (AB) has demonstrated anti-inflammatory and anti-tumor activities, yet its therapeutic potential in inflammatory bowel disease (IBD) remains unexplored. This study evaluated the efficacy of AB in dextran sulfate sodium (DSS)-induced IBD in mice by monitoring body weight, disease activity index, stool consistency, rectal bleeding, and colon length. Intestinal barrier integrity and inflammatory responses were assessed via ELISA, FITC-dextran permeability, Western blot, and immunohistochemistry. Gut microbiota composition was profiled using 16S rRNA sequencing, along with bioinformatics to predict potential mechanisms, which were subsequently validated through immunofluorescence and flow cytometry. The results showed that AB significantly mitigated body weight loss, DAI scores, colon length shortening, and splenomegaly in mice, and alleviated the pathological damage to the colon. AB strengthened intestinal barrier integrity by increasing ZO-1, Occludin, claudin-1, MUC2, and EPO levels, and reducing ET-1 and DAO levels. AB suppressed inflammation by reducing IL-1β, IL-6, and TNF-α levels, and inhibiting JAK2/STAT3 and TLR4/MyD88/NF-κB pathways. Additionally, AB rebalanced the gut microbiota by increasing beneficial bacteria (Akkermansia) and decreasing pathogenic bacteria (Bacteroides and Helicobacter). Interestingly, AB rebalanced Th17/Treg by decreasing the colonic IL-17 level, increasing IL-10, IL-22, and TGF-β levels, and reversing the proportion of Th17/Treg cells in the blood, mesenteric lymph nodes, and spleen of IBD mice. These findings demonstrate that AB mitigates DSS-induced IBD through coordinated regulation of intestinal barrier integrity, gut microbiota composition, and Th17/Treg immune balance, identifying AB as a promising candidate for IBD therapy.

Pulmonary diseases are still a serious threat to human health today, particularly in light of the recent rise of novel viruses such as SARS, influenza A, and COVID-19, which have made the situation even more dire by worsening the disease's effects on global public health. Isorhamnetin (ISO), as the active component of many medicinal plants and preparations, exhibits good antiviral, anti-inflammatory, antioxidant, and anti-tumor effects. ISO has been proven to have both preventive and treatment efficacy against pulmonary diseases. This review summarizes the effects of ISO in different pulmonary diseases, including COVID-19, pneumonia, acute lung injury/acute respiratory distress syndrome, lung cancer, asthma, pulmonary arterial hypertension, and pulmonary fibrosis, highlighting its specific molecular mechanisms against various pulmonary diseases, which is helpful for providing new perspectives on the preclinical trial and clinical application of ISO.

Rheumatoid arthritis is a chronic systemic inflammatory disease that predominantly affects synovial joints, resulting in progressive joint damage, disability, and systemic effects. There are still unanswered questions regarding the origin and pathophysiological complexities of the disease despite advances in treatment. A systematic review of the complex molecular pathways involved in RA pathophysiology is presented. Among the molecular processes involved in RA pathophysiology are oxidative stress, activation of fibroblast-like synoviocytes, aberrant innate and adaptive immunity, and dysregulated cytokine signalling. Important inflammatory signalling pathways related to the inflammation and destruction of joints including NF-κB, JAK/STAT, and RANK will be detailed. We will discuss the molecular components of the disease and the genetic and epigenetic predispositions such as HLA-DRB1 alleles, non-HLA loci, and regulation of miRNA and DNA methylation. We will highlight environmental and lifestyle related risk factors including smoking, infections, gut dysbiosis, and hormones contributing to disease manifestation and maintenance. We will describe the autoantibodies, rheumatoid factor and anti-citrullinated protein antibodies, as diagnostic and prognostic RA biomarkers. This review will summarize studies from in vivo animal models and translational studies to illustrate contemporary treatment strategies and drug development based on lessons from molecular knowledge of RA studies. Furthermore, progressive paradigms such as personalized medicine and multi-omics methodologies are discussed as potential future strategies to advance prediction, monitoring, and management of RA. This review seeks to provide an updated, broader view of the molecular biology and risk factors for RA, ultimately supporting better clinical outcomes and precision therapy.

Citrus peels, obtained from fruits belonging to the genus Citrus, of family Rutaceae, represents a major agro-industrial waste with significant nutritional and health benefits. These are composed of a variety of compounds, including flavonoids (hesperidin, naringin, quercetin, kaempferol), phenolic acids (caffeic acid, p-coumaric acid, ferulic acid, sinapic acid), essential oils, carbohydrates, amino acids and fatty acids, that can be extracted using green extraction techniques such as pulse electric field, enzyme-assisted extraction and so on. Emerging evidence highlights their numerous therapeutic benefits, including anti-diabetic, antioxidant, anti-inflammatory, anti-hyperlipidaemic and prebiotic effects. These therapeutic effects are provided through multiple pathways such as neutralising of reactive oxygen species, enhancing activity of antioxidant enzymes, suppression of inflammatory cytokines, regulation of blood pressure and blood glucose, lipid metabolism and modulation of gut microbiota. Despite the health-promising effects, existing findings rarely focus on in-vitro and in-vivo studies, primarily for antioxidant and anti-inflammatory activity. Considering the existing research gaps, this review attempts to highlight the significant potential of citrus peels, their nutritional and bioactive composition. Moreover, it examines the mechanism by which citrus peel bioactive compounds exert anti-diabetic and cardioprotective effects by reducing oxidative stress and inflammatory cytokines, with supporting in-vitro and in-vivo studies. In addition, this review investigates the synergistic effect of peels with other compounds, alongside their regulatory effects on lipid profile and gut microflora. Collectively, this review highlights the citrus peels-derived phytoconstituents as a sustainable, economic and environmentally friendly alternative for mitigation of cardiometabolic diseases including diabetes and cardiovascular disorders.

Crassula species are traditionally used and possess anti-inflammatory properties, but Crassula tetragona L. remains largely unexplored. This study intended to characterize C. tetragona aerial parts' phytoconstituents and assess its anti-ulcerative potential via the PPARγ/SIRT1 pathway. Aerial parts of C. tetragona were extracted using n-hexane (CT1) and 70% aqueous methanol (CT2). Phytoconstituents were profiled by HPLC-ESI-MS/MS (negative ion mode), and phenolics were quantified by MRM-LC-ESI-MS/MS. Column chromatography and NMR were used to separate and identify the compounds. Ulcerative colitis (UC) was induced in rats by intrarectal acetic acid (AA). Animals were assigned into six groups: control group: orally received vehicle for 7 days, UC control group: orally received vehicle for 7 days, and a rectal infusion of 2 mL AA (4% v/v in saline) on the 8th day, 4 treated groups: received CT1 (200 and 400 mg/kg/day), or received CT2 (200 and 400 mg/kg/day), once daily for 7 days by oral gavage and 2 mL AA (4% v/v in saline) on the 8th day. HPLC-ESI-MS/MS identified 66 constituents, including 37 novel compounds, with CT2 exhibiting higher phenolic content. Naringenin, gallic acid, and quercetin were predominant. Five phenolic compounds were isolated from the bioactive extract CT2. Both CT1 and CT2 reduced AA-induced tissue damage, lowered inflammatory markers (calprotectin, CRP, TNF-α, IL-6), improved oxidative stress (reduced MDA, increased GSH, SOD), and upregulated SIRT1 and PPARγ. These results suggest C. tetragona attenuates UC via the SIRT1/PPARγ pathway, indicating its therapeutic potential.

Cytokine and oxylipin profiles in rat brain homogenates were characterized as an inflammatory response 6 h after a single intracerebroventricular injection of LPS (19.3 µg LPS/ventricle), serving as a model of the inflammatory process in trauma, stroke, and similar stroke-like conditions that cause acute reactions. The potential use of 4-methylumbelliferone (4-MU), an inhibitor of hyaluronic acid (HA) synthesis, clinically approved for the treatment of bile spasm, as an anti-inflammatory drug in the early stages of the brain's response to a damaging stimulus was evaluated. i.c.v. injection of LPS induced proinflammatory genes expression (TNFα, IL-6 and IL-1β) and oxylipins synthesis. Simultaneous addition of 4-MU with LPS reduced LPS-induced TNFα, IL-1β, IL-6 release and reduced the increase in COX-derived metabolites-PGF_2α, PGE₂, 6-keto-PGF_1α, TXB₂, 12-HHT, and 15-HETE. LPS stimulated only the expression of HAS2, while the addition of 4-MU reduced the expression of LPS-stimulated HAS2, and induced the expression of HYAL1, but not HYAL2. Our results reveal significant changes in cytokines and oxylipins synthesis in the model of acute inflammation, and suggest that 4-MU can be viewed as a promising therapeutic agent in the early stages of neuroinflammation.