Inflammopharmacology最新文献

Plant-derived bioactive compounds are increasingly considered as safer alternatives to synthetic drugs in wound management. This study aimed to comparatively evaluate the wound-healing efficacy of Pistacia atlantica (bene tree) leaf extract ointment versus phenytoin in a rat skin wound model. This experimental interventional study was conducted using Pistacia atlantica leaf extract. The extract was first analyzed by gas chromatography-mass spectrometry (GC-MS) and subsequently formulated into herbal ointments. Thirty-five rats were anesthetized using ketamine and xylazine, and standardized excisional skin wounds were created on the dorsal region. Animals were randomly assigned into four groups: control (C), 5% Pistacia ointment (P5), 25% Pistacia ointment (P25), and phenytoin (F). Treatments were applied for 21 days. Wound photographs were taken on days 1, 3, 5, 7, 14, and 21, and wound areas were measured using ImageJ software. At the end of the study, tissue samples were collected in 10% formalin for histopathological analysis with hematoxylin-eosin and Masson's trichrome staining. A significant decrease in body weight was observed in the phenytoin group compared with all other groups (p < 0.05). Wound contraction and healing percentages were highest in the P25 and F groups, followed by the P5 and control groups. Histopathological analysis of P25-treated wounds, consistent with the F group, revealed a significant enhancement in epithelialization, angiogenesis, granulation tissue formation, fibroblast proliferation, collagen deposition, and hair follicle regeneration compared with the C group (p < 0.001). Furthermore, inflammatory cell infiltration during the healing process was markedly and significantly reduced in the P25 group compared to the other study groups (p < 0.001). GC-MS analysis revealed that 1,2,3-benzenetriol (antibacterial), cis-13-octadecenoic acid (anti-inflammatory), and phytol (antimicrobial, anti-inflammatory, antioxidant) were the predominant compounds in the extract. The results indicated that wound healing using an ointment containing Pistacia atlantica leaf extract occurred in a dose-dependent manner and accelerated the healing process through histopathological mechanism without adverse effects compared with phenytoin. The findings support its potential as a safe and effective phytotherapeutic alternative for wound management.

Purpose: Centaurea lycopifolia Boiss. et Kotschy (Asteraceae) is traditionally used in folk medicine for wound healing. This study aimed to develop and pharmacologically evaluate a novel oral microemulsion containing C. lycopifolia extract, focusing on its analgesic and anti-inflammatory effects in rodent models.

Methods: The extract, obtained from aerial parts of the plant, was characterized by LC-MS/MS. A microemulsion formulation was developed for oral administration. Antinociceptive activity was evaluated via hot plate (HP) and tail flick (TF) tests to assess central and spinal effects, respectively. Anti-inflammatory activity was assessed using carrageenan-induced paw edema, quantified by plethysmometry and Randall-Selitto tests.

Results: LC-MS/MS analysis identified quinic acid, chlorogenic acid, and protocatechuic acid as major phytoconstituents. In both HP and TF tests, the C. lycopifolia microemulsion demonstrated significantly stronger antinociceptive effects than aspirin. Similarly, its anti-inflammatory activity was comparable to aspirin. These pharmacological effects are possibly associated with the synergistic actions of the phenolic acids present in the extract.

Conclusions: The C. lycopifolia-loaded microemulsion exhibited strong in vivo analgesic and anti-inflammatory activity, supporting its potential as a phytopharmaceutical candidate for inflammatory pain. The use of both central and peripheral pain models provided a robust pharmacodynamic basis for its therapeutic potential. Overall, these findings highlight the relevance of phenolic-rich phytochemicals in oral delivery systems for inflammation-related disorders.

Diabetes mellitus (DM) is a chronic metabolic disorder with substantial global health implications. This study investigated the therapeutic potential of Bukiniczia cabulica (Boiss.) Lincz. against hyperglycemia and pain-related conditions. The polyphenolic profile of the crude methanolic extract (Bc.Cme) was characterized using HPLC-DAD. Its inhibitory activity against α-glucosidase and α-amylase, along with the in-silico binding affinity of identified phytochemicals, was assessed through molecular docking. The anti-diabetic effects of Bc.Cme were evaluated in alloxan-induced diabetic mice, while its antinociceptive activity was tested using tonic visceral (acetic acid-induced writhing) and acute thermal nociception (hot-plate) models. Anti-neuropathic efficacy was further examined in vincristine- and streptozotocin (STZ)-induced peripheral neuropathy. Bc.Cme demonstrated strong enzyme inhibition, suppressing α-glucosidase activity by 87.23% at 1 mg/ml and showing potent α-amylase inhibition (IC₅₀ = 29.53 µg/ml). Docking analysis supported favorable interactions between major phenolic constituents and these enzymes. In vivo, Bc.Cme (150 mg/kg) significantly reduced blood glucose levels over four weeks in alloxan-induced diabetic mice. In pain models, doses of 50-200 mg/kg markedly decreased writhing responses and increased nociceptive latency. Additionally, Bc.Cme produced dose-dependent attenuation of static and cold allodynia, as well as heat hyperalgesia, in both vincristine- and STZ-induced neuropathy models. Overall, B. cabulica exhibits notable anti-diabetic, antinociceptive, and anti-neuropathic effects, likely mediated by its polyphenolic constituents through metabolic enzyme inhibition and modulation of pain pathways. The extract shows therapeutic promise for managing DM and its associated neuropathic complications.

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.