Inflammopharmacology最新文献

Rheumatoid arthritis is an autoimmune disorder characterized by cartilage destruction, joint inflammation, and systemic complications. Incomplete disease remission, adverse effects, and limited treatment availability underscore the need for novel therapeutic interventions. With this ultimate goal, the aim of the current study was to assess the anti-inflammatory and antiarthritic potential of chloroform and ethanol extracts of Celtis eriocarpa Decne. Gas chromatography coupled with mass spectrometry (GC-MS) analysis of these extracts revealed the presence of diverse bioactive compounds with well-recognized anti-inflammatory and antiarthritic activities, including phytol, neophytadiene, tocopherols, hexadecenoic acid methyl ester, squalene, and 2-tert-butylphenol derivatives. In vitro assays demonstrated significant, dose-dependent inhibition of protein denaturation by these extracts, with the activity of the chloroform fraction comparable to that of the diclofenac sodium standard. In vivo studies in a formaldehyde-induced arthritis rat model revealed significantly reduced paw edema and arthritis scores and improved mobility after oral administration of Celtis eriocarpa chloroform extracts (CE). Radiographic analysis further confirmed joint preservation in a rat model treated with CE. Histopathological assessments indicated marked reductions in synovial hyperplasia, cartilage erosion, and inflammatory cell infiltration, specifically in the high-dose CE groups. Finally, hematological and biochemical evaluations revealed normalization of inflammatory markers, downregulation of the expression levels of key proinflammatory cytokines (TNF-α, IL-6, NF-κB, IL-1β, and COX-2), and upregulation of the expression levels of anti-inflammatory cytokines (IL-4 and IL-10). Collectively, these findings demonstrate that Celtis eriocarpa extracts are enriched in bioactive phytoconstituents and hold substantial potential as therapeutic candidates for the management of rheumatoid arthritis and inflammatory disorders.

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.

Curcuma comosa Roxb., a Thai medicinal plant, has long been used to relieve postmenopausal symptoms and is known to exhibit anti-inflammatory properties. Isocoronarin D, a labdane diterpene and the main bioactive compound in the aerial parts of C. comosa, has previously been reported to induce foetal haemoglobin synthesis. However, its anti-inflammatory activity, predicted molecular targets, pharmacokinetic characteristics, and toxicity remain insufficiently characterised. Therefore, this study integrates in silico predictions of its molecular targets, pharmacokinetic behaviour and toxicity with in vitro validation of its anti-inflammatory effects and underlying mechanisms to address these knowledge gaps. Initially, network pharmacology analysis identified protein kinase Cδ (PKCδ), phosphoinositide 3-kinase (PI3K), and cyclooxygenase-2 (COX-2) as inflammation-related targets computationally associated with isocoronarin D. These predicted targets were subsequently validated in vitro, where isocoronarin D significantly reduced the production of inflammatory mediators, including inducible nitric oxide synthase (iNOS), COX-2, tumour necrosis factor-α, interleukin (IL)-1β, and IL-6, in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Moreover, isocoronarin D inhibited the phosphorylation of PKCδ, PI3K, and Akt, indicating suppression of key inflammatory signalling pathways. The observed inhibition of these inflammatory proteins, together with the predicted interactions revealed by molecular docking, supports a mechanistically relevant role for these proteins as inflammatory targets of isocoronarin D. In addition, in silico SwissADME, pkCSM, and GUSAR analyses suggested drug-like characteristics, favourable pharmacokinetic properties, and a non-toxic safety profile. Collectively, these findings indicate that isocoronarin D exerts multi-target anti-inflammatory activity and warrants further in vivo investigation to better elucidate its therapeutic relevance in inflammation-related diseases.

Medicinal plants have been traditionally used to treat wounds. The aim of this study was to investigate the antioxidant activity, wound healing effect and chemical content of the aerial parts of Chaiturus marrubiastrum (L.) Ehrh. ex Rchb. Pressure wound model in rats was used to evaluate the wound healing effect of the extracts. The antioxidant activity of the extract was evaluated using total antioxidant capacity, reducing power, metal chelation, DPPH and ABTS scavenging tests. The chemical profile of the extract was evaluated by LC-MS/MS analysis. The extract had 83.50 ± 0.11% and 70.73 ± 1.30% inhibition in DPPH and ABTS scavenging tests, respectively. The metal chelation capacity of the extract increased with increasing concentration. The reducing power of the extract (at 2 mg/mL) was similar to that of quercetin (3.521 ± 0.07, 3.831 ± 0.03, respectively). The most abundant substance in the extract was rosmarinic acid (165.611 mg/g extract). In vivo experiments, wound healing occurred faster in the group treated with C. marrubiastrum extracts in pressure wounds created on rats compared to the control groups. Histopathological analyses showed that connective tissue development and vascularization increased and inflammation decreased in this group. In addition, immunohistochemical analyses have shown that C. marrubiastrum extract reduces TNF-α, VEGF and caspase-3 levels, thus inhibiting inflammation and apoptosis. These findings suggest that the wound healing-accelerating effects of C. marrubiastrum are based on strong antioxidant and anti-inflammatory properties. It is concluded that future studies should optimize this extract for clinical use and evaluate its efficacy in humans.

Huntington's disease (HD) is a progressive neurodegenerative disorder in which neuroinflammation, oxidative stress, and mitochondrial dysfunction are increasingly recognized as important contributors to neuronal vulnerability. Recent evidence indicates that the ATP-gated P2X7 receptor (P2X7R) may participate in coordinating several of these pathological processes. Under conditions of cellular stress, elevated extracellular ATP can promote sustained activation of P2X7R, leading to Ca²⁺ influx, mitochondrial depolarization, and enhanced production of reactive oxygen species (ROS), in part through NADPH oxidase-dependent mechanisms. This oxidative environment is associated with lipid peroxidation and the generation of electrophilic aldehydes, such as 4-hydroxynonenal and malondialdehyde, which have the potential to influence chromatin organization and disrupt histone modifications, thereby contributing to altered transcriptional regulation. In parallel, activation of P2X7R in microglia has been linked to NLRP3 inflammasome activation and the release of pro-inflammatory cytokines, including IL-1β and IL-18, which may further exacerbate neuroinflammatory signaling. Together, these observations support the hypothesis of a P2X7-redox-lipid-epigenetic axis that could contribute to neuronal susceptibility and striatal pathology in HD. Preclinical studies suggest that inhibition of P2X7R can attenuate neuroinflammation, improve mitochondrial function, and partially ameliorate behavioral deficits in experimental models. In addition, the development of brain-penetrant P2X7R antagonists and P2X7-specific PET tracers provides emerging opportunities for translational research, biomarker development, and therapeutic monitoring. Overall, P2X7R represents a promising, though still exploratory, therapeutic target in HD.

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.

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.