Inflammopharmacology最新文献

Myocardial ischemia, resulting from coronary artery blockage, precipitates cardiac arrhythmias, myocardial structural changes, and heart failure. The pathophysiology of MI is mainly based on inflammation and cell death, which are essential in aggravating myocardial ischemia and reperfusion injury. Emerging research highlights the functionality of high mobility group box-1, a non-histone nucleoprotein functioning as a chromosomal stabilizer and inflammatory mediator. HMGB1's release into the extracellular compartment during ischemia acts as damage-associated molecular pattern, triggering immune reaction by pattern recognition receptors and exacerbating tissue inflammation. Its involvement in signaling pathways like PI3K/Akt, TLR4/NF-κB, and RAGE/HMGB1 underscores its significance in promoting angiogenesis, apoptosis, and reducing inflammation, which is crucial for MI treatment strategies. This review highlights the complex function of HMGB1 in the pathogenesis of myocardial infarction by summarizing novel findings on the protein in ischemic situations. Understanding the mechanisms underlying HMGB1 could widen the way to specific treatments that minimize the severity of MI and enhance patient outcomes.

Volatile oils (VOs), synonymously termed essential oils (EOs), are highly hydrophobic liquids obtained from aromatic plants, containing diverse organic compounds for example terpenes and terpenoids. These oils exhibit significant neuroprotective properties, containing antioxidant, anti-inflammatory, anti-apoptotic, glutamate activation, cholinesterase inhibitory action, and anti-protein aggregatory action, making them potential therapeutic agents in managing neurodegenerative diseases (NDs). VOs regulate glutamate activation, enhance synaptic plasticity, and inhibit oxidative stress through the stimulation of antioxidant enzymes. They also reduce inflammation by inhibiting key inflammatory mediators and enzymes. Furthermore, VOs prevent neuronal apoptosis by modulating apoptosis-related proteins and caspases. Their anti-protein aggregation potential helps mitigate the accumulation of misfolded proteins, a hallmark of neurodegenerative disorders. Additionally, VOs inhibit cholinesterase enzymes, increasing acetylcholine levels, and improving neuronal communication. In addition to their neuroprotective action, it also exerts some toxic effects, such as genotoxicity, hepatotoxicity, embryotoxicity, and hypersensitivity, which are most commonly caused by the presence of monoterpenes in the volatile oils. This review examines the diverse functions of vasoactive oxidants (VOs) in neuroprotection, underscoring their therapeutic promise for various neurological conditions, with a particular emphasis on Alzheimer's disease.

Stroke is a serious life-threatening medical condition. Understanding the underlying molecular mechanisms of this condition is crucial to identifying novel therapeutic targets that can improve patient outcomes. Autophagy is an essential mechanism for the destruction of damaged intracellular components that maintains homeostasis in physiological or pathological conditions. This process is involved in the pathophysiology of stroke. Phytochemicals are bioactive naturally occurring compounds present in plants. This paper reviews the neuroprotective roles of phytochemicals in ischemic stroke through autophagy modulation. It summarizes the interactions of various phytochemicals with key molecular targets of the autophagy pathway in ischemic stroke, including PI3K/Akt/mTOR, Beclin-1, and AMPK. Due to the ability of various phytochemicals to alter autophagic flux, they may provide promising opportunities in the development of new treatments and the improvement of stroke management.

Alzheimer's disease (AD) stands out as the foremost prevalent neurodegenerative disorder, characterized by a complex etiology. Various mechanisms have been proposed to elucidate its onset, encompassing amyloid-beta (Aβ) toxicity, tau hyperphosphorylation, oxidative stress and reactive gliosis. The hallmark of AD comprises Aβ and tau aggregation. These misfolded protein aggregates trigger the activation of glial cells, primarily microglia. Microglial cells serve as a major source of inflammatory mediators and their cytotoxic activation has been implicated in various aspects of AD pathology. Activated microglia can adopt M1 or M2 phenotypes, where M1 promotes inflammation by increasing pro-inflammatory cytokines and M2 suppresses inflammation by boosting anti-inflammatory factors. Overexpressed pro-inflammatory cytokines include interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in adjacent brain regions. Furthermore, microglial signaling pathways dysregulated in AD are myeloid differentiation primary-response protein 88 (Myd 88), colony-stimulating factor-1 receptor (CSF1R) and dedicator of cytokinesis 2 (DOCK2), which alter the physiology. Despite numerous findings, the causative role of microglia-mediated neuroinflammation in AD remains elusive. This review concisely explores cellular and molecular mechanisms of activated microglia and their correlation with AD pathogenesis. Additionally, it highlights promising therapeutics targeting microglia modulation, currently undergoing preclinical and clinical studies, for developing effective treatment for AD.

Alzheimer's disease is a devastating neurodegenerative disorder that affects millions of people worldwide. One of the key pathological features of Alzheimer's disease is oxidative stress, which is characterized by an imbalance between the production of reactive oxygen species and the body's ability to neutralize them with antioxidants. In recent years, there has been growing interest in the potential role of antioxidant supplementation in mitigating oxidative stress markers in Alzheimer's disease. This review paper aims to provide a comprehensive overview of the current research on antioxidant supplementation in Alzheimer's disease and its effects on oxidative stress markers. The paper will examine the underlying mechanisms of oxidative stress in Alzheimer's disease, the potential benefits of antioxidant supplementation, and the challenges and limitations of using antioxidants as a therapeutic strategy.

Background: Rosacea is a chronic inflammatory disease characterized by persistent erythema, papules, and pustules, mainly on the skin of the face. Rosacea is difficult to treat; therefore, identifying new treatments is crucial. Mas-related G protein-coupled receptor X2 (MRGPRX2)-mediated mast cell (MC) activation is essential in the pathogenesis of rosacea. Casticin has been shown to exert anti-inflammatory effects; however, it remains unclear whether it can inhibit MRGPRX2 in treating rosacea. This study determined the therapeutic efficacy of casticin against rosacea by inhibiting MRGPRX2-mediated MC activation.

Methods: A mouse model of LL37-induced rosacea-like dermatitis was employed. The pathological changes were evaluated using hematoxylin and eosin (H&E) staining, and MCs and CD4⁺ T cells were observed. Inflammatory mediators were analyzed using ELISA. Mouse skin lesions were collected for transcriptomic sequencing. We used an MRGPRX2-mediated MC degranulation model to evaluate the inhibitory effects of casticin in vitro. Molecular docking analysis, molecular dynamics simulations, and surface plasmon resonance evaluated the binding between casticin and MRGPRX2.

Results: Casticin attenuated the LL37-induced inflammatory phenotype and reactions in rosacea-like dermatitis. RNA-seq data showed that casticin inhibited MC activation in a mouse model of rosacea. Furthermore, casticin significantly reduced CD4 + T-cell infiltration. Moreover, casticin inhibited MC activation as an MRGPRX2 antagonist in vitro and in vivo by influencing the NF-κB signaling pathway.

Conclusion: Our study demonstrated that casticin exhibits therapeutic efficacy against rosacea by inhibiting MC activation via MRGPRX2.

Background: Montanoa grandiflora, a plant species native from Mexico to Central America, locally known as "Teresita" in Yucatán, México, is used to alleviate anxiety, rheumatism, and stomach issues. This study aims to investigate the anti-inflammatory properties of the methanol extract of Montanoa grandiflora leaves (MMG) in experimental models of inflammation.

Methods: Gas chromatography-mass spectroscopy was used to characterize the MMG; cytotoxicity was assessed by MTT assay on murine macrophages and hemolysis assay. The in vitro anti-inflammatory activity was evaluated on LPS-stimulated murine macrophages by measuring of pro- and anti-inflammatory cytokines, NO and H₂O₂ release. The in vivo anti-inflammatory activity was evaluated using carrageenan-induced mouse paw edema, 12-O-tetradecanoylphorbol 13-acetate induced-ear edema, and 1-fluoro-2,4-dinitrobenzene induced-delayed-type hypersensitivity. In addition, the serum levels of prostaglandins and leukotrienes were assessed.

Results: The main compounds found in MMG were terpenes (i.e., β-caryophyllene, (-)-α-cubebene, alloaromadendrene, ( +)-δ-cadinene, β-eudesmol), alkaloid (( ±)-nor-β-hydrastine), cyclic polyol (quinic acid), carbohydrates and their derivatives, and fatty acids (octadecatrienoic acid and octadecanoic acid). MMG did not exhibit cytotoxic or hemolytic activity. However, it demonstrated in vitro anti-inflammatory effects by increasing the production of IL-10, decreasing the levels of TNF-α, IL-1β, IL-6, NO and H₂O₂. MMG significantly reduced carrageenan-induced paw edema, TPA-induced ear edema, and DNFB-induced delayed-type hypersensitivity in mice with effects comparable to those of standard drugs, as well as serum levels of prostaglandins and leukotrienes.

Conclusion: The anti-inflammatory activity of MMG is associated with increased IL-10 levels and inhibiting inflammatory cell migration mechanisms, without causing cytotoxic or hemolytic damage in both in vitro and in vivo assays.

Background: Osteoarthritis (OA) is a common joint disorder causing pain and stiffness, with limited effective treatment options. Methotrexate, known for its anti-inflammatory properties in rheumatoid arthritis, is being explored as a treatment for OA. This study evaluates Methotrexate's efficacy compared to placebo in reducing OA symptoms, such as stiffness in the knee and hand, and its impact on pain, physical function.

Methods: We systematically searched PubMed, Google Scholar, Embase, Web of Science, and Cochrane databases for randomized controlled trials (RCTs), analyzing the efficacy of Methotrexate compared to placebo in patients with OA. We pooled risk ratios (RR) for binary outcomes. For continuous outcomes, we used standard mean difference (SMD) and mean difference (MD) with 95% confidence intervals (CI). Outcomes included were related to knee and hand pain, knee stiffness, and similar outcomes. We used R version 4.4.1 for statistical analyses. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach evaluated the quality of evidence.

Results: This analysis included 5 RCTs comprising 465 patients, of whom 229 were randomized to Methotrexate. The age ranged from 52.4 to 67.5 years among studies. Compared with placebo, Methotrexate significantly reduced knee and hand stiffness at the end of follow-up (SMD - 0.36; 95% CI - 0.57 to - 0.15; p< 0.01), knee and hand stiffness at 6 months of follow-up (SMD - 0.48; 95% CI - 0.70 to - 0.27; p< 0.01).

Conclusion: Methotrexate significantly reduced knee stiffness in both knee and hand OA. However, current literature might be underpowered, more robust RCTs are necessary to validate these findings.

Background: Capsaicin (CAP) induces transient pain sensation by activating transient receptor potential vanilloid-1 (TRPV1). However, the initial neuronal excitation induced by CAP is followed by a prolonged refractory period, resulting in long-lasting analgesia. Although the effects of CAP on microglia in the dorsal root ganglion of neuropathic pain disorders have been reported, the regulatory pathways of CAP on microglia remain poorly defined.

Methods: A chronic pain model was established via plantar injection of complete Freund's adjuvant (CFA), and different doses of CAP were administered to rats. Pain behavior, expression of pain-related factors, protein expression of TRPV1 in nerve cells, and the inflammatory activation of microglia were evaluated. In vitro experiments were conducted to explore the activation and migration ability of microglia, expression of inflammatory cytokines and pathway proteins, TRPV1 expression in nerve cells, and intracellular calcium concentration under different doses of CAP.

Results: Different doses of CAP alleviated chronic pain in rats, reduced TRPV1 expression in nerve cells, and inhibited the activation of microglia; however, high doses of CAP were particularly effective in improving chronic pain. In vitro experiments confirmed that CAP reduces the secretion of inflammatory cytokines by microglia via inhibition of the TLR4/AKT/NF-κB signaling pathway. This mechanism reduced the injury and apoptosis of nerve cells, the expression of TRPV1, and the influx of calcium ions in nerve cells.

Conclusions: CAP reduced inflammatory responses in microglia in a dose-dependent manner by inhibiting the TLR4/AKT/NF-κB signaling pathway, which consequently reduced TRPV1 expression on neuronal cells and reduced chronic pain.

Palmitoylethanolamide (PEA) is emerging as a promising therapeutic agent for neuropathic and other pain-related conditions. This naturally occurring fatty acid has drawn interest because of its ability to regulate pain and inflammation. Initially identified in food sources, PEA has been the subject of extensive research to elucidate its properties, efficacy, and clinical applications. PEA primarily exerts its effects through interaction with its primary receptor PPAR α, this interaction influences pain signalling pathways and neuroinflammatory processes by modulating the synthesis of pro-inflammatory cytokines, mast cell degranulation, microglial activation, and decrease of oxidative stress. PEA's interaction with endocannabinoid receptors decreases the inflammatory cytokine and chemokine production and thereby a descending pain sensation. The pharmacological and pharmacokinetic characteristics of PEA are examined in this paper, along with its potential for efficiency when used in in combination additional therapies in a variety of neurodegenerative disease models, including multiple sclerosis, Parkinson's disease, and Alzheimer's. Experimental evidence shows that PEA not only reduces pain and inflammation but also lowers the need for higher dosages of other drugs hence minimizing the risk of drug toxicity. The bioavailability of PEA has been enhanced by recent technological developments, which emphasize continuous research efforts to maximize PEA's therapeutic potential in pain treatment and associated medical sectors.