Inflammopharmacology最新文献

Protease-activated receptors (PARs) constitute a unique subfamily of G protein-coupled receptors comprising four members, PAR1-PAR4. PAR, which govern a broad spectrum of physiological and pathological processes. This review provides a comprehensive synthesis of the roles of PARs in mediating both metabolic dysfunction and inflammatory responses, exploring their potential as dual-function therapeutic targets. We analyze the current literature regarding PAR activation mechanisms and downstream signaling pathways, with a specific focus on their involvement in metabolic syndrome and inflammatory diseases. By evaluating experimental data from genetic ablation and pharmacological inhibition models, we demonstrate that while PAR activation often drives disease progression, targeted inhibition can successfully alleviate symptoms and delay pathogenesis. Ultimately, this review underscores the critical role of PARs in bridging metabolic and inflammatory crosstalk, suggesting that modulating these receptors offers a promising strategy for dual regulation of systemic homeostasis.

Non-healing wounds, such as diabetic foot ulcers, burns, and pressure injuries, represent a persistent clinical challenge, affecting an estimated 2-5% of the global population and accounting for annual healthcare costs exceeding USD 25 billion. Their failure to heal is driven by unresolved inflammation, inadequate vascularization, and progressive disorganization of extracellular matrix (ECM) architecture, which collectively disrupt the coordinated cascade of tissue regeneration. Mesenchymal stem cell (MSC)-derived exosomes have emerged as a potent cell-free therapeutic approach capable of addressing these pathological barriers through multi-level biological modulation of immune, vascular, and stromal compartments. Preclinical studies demonstrate that topical or injectable administration of MSC-derived exosomes accelerates wound closure by 25-60% within 10-14 days compared to controls. Immunomodulatory effects include promoting macrophage polarization from M1 to M2 phenotypes, with reported increases in M2/M1 ratios of 1.5-3.2-fold, mediated by exosomal miRNAs (e.g., miR-223, miR-181c) and proteins that suppress NF-κB signaling. Angiogenesis is markedly enhanced, with microvascular density rising by 30-70%, driven by the transfer of VEGF, miR-126, and miR-21 to endothelial cells, thereby boosting migration and tube formation. Fibroblast activity is similarly upregulated, resulting in 1.4-2.0-fold increases in collagen deposition and restoration of the MMP/TIMP balance, leading to improved tensile strength and ECM integrity. Integration of biomaterial-assisted delivery platforms, including thermosensitive hydrogels, collagen scaffolds, and microneedle arrays, extends exosome retention and functional bioavailability at the wound site by 2-5 times compared to free vesicles. While early clinical trials report safety and feasibility, challenges in large-scale GMP manufacturing, batch-to-batch consistency, and regulatory harmonization. Overcoming these translational barriers through advances in bioengineering, genetic modification, and smart delivery systems may enable the evolution of MSC-derived exosomes into standardized, next-generation therapeutics for chronic, non-healing wounds.

Background: Elderberry (Sambucus nigra L.) has been traditionally implemented in diverse preparations such as herbal teas, syrups or juices as remedies for respiratory, febrile and other health conditions. Phytochemical and chromatographic analyses of different organs mapped their metabolite profiles and allowed identification, and sometimes isolation, of their main bioactive compounds.

Aim of the study: Inspired by the rich and effective literature of S. nigra, this review article aims to summarize and highlight its reported biological (traditional and research-based) and chemical profiles.

Methods: The Keywords used in the search included biological activities, pharmacological reports, phytochemistry, isolated compounds, taxonomy, botanical data, single or combination; traditional, traditionally, ethnopharmacology, folk uses, toxicity, LD50, interactions, side effects, clinical studies, elderberry, elder, Sambucus nigra. Using different bibliographic databases, Google Scholar, PubMed, Web of Science, Springer Link, and Science Direct with no specific limits.

Results: In this context, elderberry is deemed a rich source for a myriad of bioactive compounds, mainly phenolics, and was proven to exhibit a variety of health benefits, including antioxidant, anti-inflammatory, anticancer, anti-influenza, antimicrobial, antidiabetic, cardioprotective, and neuroprotective properties. This review also covers different analysis approaches applied for S. nigra characterization in addition to literature studies attempted to optimize its extract(s) preparation process in terms of different extraction solvents, temperatures or methodologies to enrich prepared extracts in beneficial and bioactive metabolites.

Conclusion: Overall, elderberry holds substantial potential as a rich dietary source of bioactive metabolites. Future research into its application in functional foods and nutraceuticals may provide innovative strategies for the prevention and management of various chronic diseases.

Clinical trial number in the manuscript: Not applicable.

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.