Inflammopharmacology最新文献

Background: Animal venoms are rich in bioactive peptides with potential therapeutic properties. Among marine toxins, jellyfish venoms are underexplored for anti-inflammatory applications. This study aims to identify and evaluate a peptide derived from the jellyfish toxin CfTX-B, for its anti-inflammatory potential.

Methods: Peptide selection was conducted through an integrated computational-experimental workflow comprising PeptideRanker bioactivity prediction, ToxinPred toxicity screening, SwissADME pharmacokinetic evaluation, and multi-target molecular docking against NLRP3, caspase-1, XO, and IL-1β, followed by LC-MS/MS confirmation of proteolytic stability. The peptide's antioxidant activity was validated through XO inhibition assays. Cytotoxicity and anti-inflammatory effects were tested in human dermal fibroblasts (HDFs) co-stimulated with lipopolysaccharide (LPS) and monosodium urate (MSU) crystals. FITC-labeling studies assessed intracellular peptide uptake. Further, the inflammation suppressing effects of the peptide were studied on in vivo rat model of gouty arthritis.

Results: The CfTX-B derived tetrapeptide (WPAW) revealed highest predicted bioactivity scores, favorable ADMET characteristics, and resistance to simulated gastrointestinal digestion. The peptide also showed strong binding to NLRP3, caspase-1, XO, and low predicted toxicity. XO inhibition assays confirmed antioxidant activity. In HDFs, the peptide showed no cytotoxicity up to 125 µM. Treatment with peptide significantly reduced nitric oxide (14.05 ± 0.24 µM) and reactive oxygen species (0.32 ± 0.009 RFI). ELISA revealed lowered IL-1β levels (53.54 ± 3.05 pg/ml). Protein expression studies showed downregulation of NLRP3, and pP65 levels, indicating effective suppression of inflammasome activation. The peptide reduced serum XO activity, IL-1β levels and suppressed joint inflammation in gout induced rats.

Conclusions: The tetrapeptide derived from jellyfish venom, exhibits strong anti-inflammatory and antioxidant activity through NLRP3 inflammasome inhibition. These results support its potential for development as a therapeutic for chronic inflammatory diseases.

Background: New targeted drugs, including biologics and Janus kinase inhibitors (JAKi), have been approved for the treatment of atopic dermatitis (AD). Given their widespread clinical use, a comprehensive real-world study of their adverse events (AEs) is warranted.

Objectives: This study aims to characterize of new targeted drugs related AEs, and to compare the AE profiles of biologics and JAKi.

Methods: Disproportionality metrics, including the reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean, were employed to determine AE signals. The most recent case reports were all included, and data was included until third quarter of 2024.

Results: A total of 99,043 biologics-related and 3,897 JAKi-related AEs were identified. Biologics-specific AEs, including injection reaction and eye disorders, were worthy noted. Several JAKi specific AEs also need to be noticed, including infection, gastrointestinal perforation, precancerous condition, pulmonary thrombosis, embolism venous, and pulmonary tuberculosis. Biologics exhibited more number of positive AE signals compared to JAKi, but the serious AEs are more frequently reported in JAKi than biologics (P < 0.01).

Conclusion: Our study could provide a comprehensive safety overview of biologics and JAKi during AD treatment, and provide valued evidence for healthcare professionals to select these drugs for AD patients.

Introduction: Tecoma stans (T. stans) is traditionally employed in folk medicine for the management of inflammatory conditions; however, its pharmacological properties and underlying mechanisms of action remain insufficiently characterized.

Aim: This study aimed to evaluate the anti-inflammatory, antioxidant, and cytoprotective effects of the methanolic flower extract of T. stans using both in vitro and in vivo models, with particular emphasis on cytokines, modulation, oxidative stress markers, and lipid-derived inflammatory mediators.

Methodology: Cytotoxicity and hemotoxicity were assessed using MTT reduction and hemolysis assays, respectively. Anti-inflammatory activity was evaluated employing carrageenan-induced paw oedema and xylene-induced ear oedema models. Modulation of cytokine (TNF-α, IL-1β, IL-6, IL-10) was determined in both in vivo and in vitro models. Additionally, the effects of the extract on nitric oxide (NO), hydrogen peroxide (H₂O₂), leukotriene B₄ (LTB₄), and prostaglandin E₂ (PGE₂) production were analyzed.

Results: T. stans extract exhibited no cytotoxic or hemolytic effects, maintaining cell viability above 90%. It significantly attenuated inflammatory responses in edema models, reduced pro-inflammatory cytokines and mediator levels, and increased IL-10 production. Furthermore, the extract markedly decreased NO and H₂O₂ generation, indicating a reduction in oxidative stress.

Conclusions: These findings support the anti-inflammatory and antioxidant potential of T. stans, mediated through cytokine modulation, attenuation of oxidative stress, and partial inhibition of COX/LOX pathways. Collectively, its pharmacological profile highlights its potential as a natural therapeutic agent for the management of inflammatory disorders.

Inflammation and oxidative stress are involved in the physiological changes associated with many chronic diseases, which has led to sustained interest in small molecules with pleiotropic properties. As part of this effort, this study reports the synthesis and evaluation of six chalcones. These six synthesized derivatives were produced using acetophenone and benzaldehyde, and structures were characterised through nuclear magnetic resonance (NMR) spectral analysis and Fourier transform infrared (FTIR) spectroscopy. The compounds were tested for their in-vitro antioxidant properties using the DPPH free radical scavenging assay and anti-inflammatory and analgesic properties using an in-vivo model in rats and carrageenan-induced paw edema, heat-induced hyperalgesia, and mechanical allodynia.Computational finding by using AutoDockVina protocol against target enzyme (COX-II) (PDB: 3LN1), where the compounds 3B, 2B, and 1A exhibited strong binding affinities of - 9.8 kcal/mol, - 9.2 kcal/mol, and - 9.2 kcal/mol, respectively.Among these compounds, compound 3B exhibited the highest antioxidant activity, demonstrating an efficacy percentage of 78.34% and an IC₅₀ value of 7.86μg/ml. The chalcone derivatives were also assessed for their effectiveness in carrageenan-induced hyperalgesia, a model used to study pain response. Compound 1A significantly increased latency periods at 30, 60, 90, and 120 min compared to compounds 2B and 3B, suggesting its potential analgesic properties. Furthermore, compound 3B significantly reduced allodynia response at 120 min, indicating its potential to alleviate mechanical sensitivity.These findings suggest that chalcone derivatives, particularly 2B and 3B, hold strong potential as lead compounds for developing novel COX-2-targeted anti-inflammatory and antioxidant therapeutics. This study offers a comprehensive preclinical framework for chalcone-based drug discovery targeting inflammation and oxidative stress. This study emphasizes structure-dependent variations in chalcones, which present potential leads and are worthy of further exploration.

Microglial cells play a pivotal role in the different CNS related conditions as they have the power to destruct as well protect the Central Nervous System. Depending on the environment they are in, they respond to different stimuli and carry out a function. Majority of the cases, the microglial cells are activated which cause inflammation to a very large extent and for a prolonged period of time which causes the various signs and symptoms of the neurodegenerative disorders. Cannabinoid Type-2 (CB2) receptor crosstalk is a key modulator of microglial plasticity, influencing both pro-inflammatory and anti-inflammatory states in the brain. Activation of CB2 receptors in microglia can suppress neurotoxic inflammation, promote anti-inflammatory phenotypes, and facilitate microglial migration and environmental surveillance. By shifting microglial polarization away from pro-inflammatory states, CB2 stimulation helps control neuroinflammation and supports tissue repair in neurodegenerative and neuroinflammatory conditions. This intricate crosstalk highlights CB2 as a promising therapeutic target for managing central nervous system dysfunctions mediated by microglial activity. The present review discusses CB2 receptor crosstalk and its role in microglial plasticity and neuroinflammation.

PKC-NF-κB-NLRP3 inflammasome axis and its non-coding RNA (ncRNA) regulatory network triggers robust innate immune activation and neuroinflammation, culminating in neuronal apoptosis and death during Global cerebral ischemia (GCI). The present mechanistic overview illustrates how condensed and hydrolysable tannins, along with related polyphenols, modulate such regulatory network to confer neuroprotection. Ischemia-associated danger signals activate Toll-like receptor-2 (TLR2) through di/tri-acylated lipopolysaccharides, engaging MyD88 and TRAF6 to stimulate protein kinase C (PKC). PKC activation promotes nuclear factor-κB (NF-κB) signaling, leading to interleukin-1β (IL-1β) production and priming of the NLRP3 inflammasome. Subsequent caspase-1 activation drives neuroinflammation and neuronal apoptosis, ultimately resulting in neuronal death. Compounds such as tannic acid, punicalagin, corilagin, pedunculagin, chebulagic acid, chebulinic acid, castalagin, and epigallocatechin gallate (EGCG) suppress NF-κB/IL-1β signaling, while tellimagrandin II, procyanidin C1/B2, paeoniflorin gallate, rosmarinic acid, and savinin directly inhibit NLRP3 activation. Additional phytochemicals, including baicalin and carnosic acid, attenuate upstream PKC signaling. Crucially, these effects are fine-tuned by ncRNAs: miR-146a and miR-155/lncRNA TUG1 regulate NF-κB activity, miR-124 and miR-223 constrain PKC and NLRP3 signaling, and lncRNA NEAT1 modulates caspase-1 activation. Collectively, the integrated suppression of PKC/NF-κB/NLRP3-ncRNA neuroinflammatory signaling by tannins limits inflammasome activation, reduces neuronal apoptosis, and mitigates ischemia-induced neuronal loss. This framework underscores tannins as promising multi-target neuroprotective agents for GCI.

Polycystic ovary syndrome (PCOS) is a common gynaecological disorder, clinically characterized by chronic anovulation and hyperandrogenism. Despite its high prevalence, no curative treatment exists, and managing the syndrome remains challenging. A strong association between PCOS and metabolic syndrome, particularly insulin resistance, adversely influences fertility, leading to an increased worldwide demand for advanced treatment options. Although the exact aetiology and pathophysiology of the syndrome remain unclear, an intricate interaction of ovarian, endocrine, and metabolic factors is highly likely. During the last two decades, several pathophysiological factors have been identified, and growing evidence suggests that PCOS is not solely a reproductive endocrinologic disorder but a multisystem syndrome with reproductive, endocrine, metabolic, and psychiatric manifestations. Diagnostic criteria such as the Rotterdam criteria, the NIH-NIHCD criteria, and the Androgen Excess Society (AES) criteria have uncovered a wide spectrum of clinical manifestations. Lifestyle modification and insulin sensitizers remain the gold standard for management in obese PCOS women. Emerging therapeutics include novel insulin-sensitizing agents, such as glucagon-like peptide 1 receptor agonists, sodium-glucose co-transporter 2 inhibitors, and dipeptidyl peptidase-4 inhibitors. Nutraceuticals and herbal remedies, surgical interventions, which have undergone modifications and refinements over time, facilitate follicle growth by increasing endogenous gonadotropin secretion as an alternative to ovulation induction in clomiphene-resistant PCOS women. Treatment of infertility resulting from PCOS is demanding, and current approaches are neither uniformly successful nor universally accepted. Future directions involve exploring the potential of vaginal microbiota and photothermogenesis for comprehensive management.

Dry eye disease (DED), a disorder with multiple contributing factors, is marked by instability in the tear film, increased osmolarity, and inflammatory responses. This research investigates the therapeutic potential of essential oil derived from wild chrysanthemum essential oil (CHEO) in treating DED. GC-MS analysis identified 121 bioactive compounds in CHEO, including L-borneol (6.00%) and β-sitosterol (4.60%), compounds with established anti-inflammatory properties. In human corneal epithelial cells subjected to hyperosmotic stress, CHEO treatment significantly improved cell viability and lowered inflammatory cytokines (IL-1β, IL-6, TNF-α) secretion. CHEO administration was demonstrated to restore tear production, improve corneal epithelial integrity, and increase conjunctival goblet cell density in scopolamine-induced DED mice. Notably, the ocular tissues demonstrated suppression of mitogen-activated protein kinases (MAPK) and NF-κB pathway activation by CHEO. The collective evidence indicates that CHEO alleviates DED through multimodal mechanisms involving anti-inflammatory action and ocular surface protection, highlighting its promise as a new phytotherapeutic option for managing DED.