Inflammopharmacology最新文献

The prevalence of gastrointestinal disorders caused by alcohol, Helicobacter pylori, non-steroidal anti-inflammatory drugs, chronic stress and sedentary lifestyle is on the rise. Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, has emerged as a protective factor against various gastrointestinal issues. Despite its known benefits, the dual role of CGRP in gastrointestinal damage remains unclear. Discovered 30 years ago through alternative RNA processing of the calcitonin gene, CGRP is known to be a potent vasodilator involved in crucial defensive mechanisms for both physiological and pathological conditions. Promising evidences from preclinical research have attracted the interest of scientists for the exploration of CGRP as a therapeutic neuropeptide. Numerous evidences suggest that this neuropeptide is secreted by the neurons under the influence of endogenous as well as exogenous stimuli. CGRP repairs the gastric mucosal barrier and maintain mucosal integrity by suppressing NF-κB activation, thereby reducing tumour necrosis factor-alpha expression. In addition, recent studies suggest that CGRP modulates immune responses and enhances epithelial cell proliferation, further contributing to its cytoprotective effects. Consequently, CGRP and the CGRP secretagogues represent promising novel targets for clinical applications. This review aims to elucidate the role of CGRP and CGRP secretagogues in the management of gastrointestinal disorders, highlighting its potential as a therapeutic agent in the context of evidence-based modern gastroenterology.

Inflammation is a necessary immunological response that promotes survival and preserves tissue homeostasis, a common characteristic linked to various diseases. However, in some circumstances, the inflammatory response is deleterious and contributes to disease pathogenesis. Anti-inflammatory substances have poor affinity for inflamed tissues, resulting in low concentrations in the target tissue and a higher incidence of severe adverse effects. To address this issue, several potential approaches have been proposed, such as chemical modification of drug molecules and the development of nanocarriers for drug delivery. Since the development of nanotechnology at the beginning of the twenty-first century, researchers have been using the pathophysiological characteristics of inflammation, primarily leaky vasculature, and biomarker overexpression to develop nanomedicines that can deliver therapeutics via passive and active targeting mechanisms to sites of inflammation and produce therapeutic effects. Drug carriers based on nanoparticles can enhance the safety and efficacy of drugs by increasing their capacity, enhancing their solubility, combining several drugs, protecting them from metabolism, and regulating their release. An approach that shows promise in the treatment of various inflammatory diseases is the application of nanomedicines. Nanomedicine involves nanoparticles that have been loaded with a therapeutically active component. Nanomedicines can target inflammation by recognizing molecules highly expressed on endothelial cells or activated macrophage surfaces, enhancing the permeability of vessels, or even by biomimicry. A review of the research findings shows significant potential for the use of nanotechnology to enhance the quality of life for people using NSAIDs for chronic disorders by minimizing drug side effects or the duration of administration. After a brief introduction to inflammation, its various forms- acute and chronic inflammation, and the pathophysiology of inflammation, this review highlights the main innovative nanocarriers utilized for carrying various nonsteroidal anti-inflammatory drugs that have been utilized in treating various inflammatory disorders.

Atopic dermatitis (AD) is a paradigmatic prevalent, long-lasting, and inflammatory skin condition with a diverse range of clinical manifestations. The etiology and clinical symptoms of AD are influenced by complex pathophysiological processes, which involve a strong genetic component, epidermal dysfunction, and immunological dysregulation, and a strong influence of other physiological and environmental factors. The FDA has approved targeted and well-tolerated immunomodulators including biologics like dupilumab and crisaborole, and small molecules such as baricitinib, as novel therapies for AD. They effectively treat AD but are too expensive for most patients. The review provides an update on the state of knowledge of AD pathogenesis, discusses the available diagnostic and scoring indices, and provides a scientific foundation for treatment methods for AD. This review also presents data on clinical efficacy of innovative treatments' considering recent guidelines, emphasizing the newest medications and ongoing trials. Finally, the new implication of artificial intelligence (AI) in AD management is explored, where AI can speed up diagnosis and therapy. The PubMed, Google Scholar, and ScienceDirect databases were used for this review.

Aim of the study: This study examined vitexin's effect on sepsis-induced acute lung injury. We used network pharmacology and in vivo and in vitro experiments were performed to elucidate vitexin's role in preventing pyroptosis and regulating small nucleolar RNA host gene 1 (SNHG1)/DNA methyltransferase 1 (DNMT1)/microRNA-495 (miR-495 axis.

Materials and methods: We developed an acute lung injury model using C57BL/6 mice and MLE-12 cells. Through a combination of network pharmacology and in vitro screening, vitexin was identified as the most promising anti-inflammatory compound. Multiple techniques such as western blotting, real-time PCR, Hematoxylin and eosin staining, immunohistochemistry, and TUNEL assay were used. Additionally, immunofluorescence, DCFDA and TMRE staining, flow cytometry, methylation-specific PCR, and gene transfection techniques were performed to elucidate vitexin's potential targets and underlying mechanisms.

Results: Vitexin treatment significantly reduced lung damage, neutrophil infiltration, and inflammation while improving tight junction integrity. In LPS-treated RAW264.7 macrophages and a septic mouse BALF-induced MLE-12 cell injury model, vitexin demonstrated anti-inflammatory effects, promoted M2 macrophage polarization, and enhanced regenerative markers. It also decreased oxidative stress, mitigated apoptosis and pyroptosis, and improved mitochondrial function. Our research uncovered a novel epigenetic regulatory mechanism involving lncRNA SNHG1, DNMT1, and miR-495.

Conclusion: Vitexin's ability to reduce inflammation, counteract oxidative stress, and modulate epigenetic processes. These findings underscore the promising role of vitexin as a treatment for ALI generated by sepsis. The SNHG1/miR-495 axis, which has been identified, represents a new target for future therapies in acute lung injury.

The venom peptides from terrestrial as well as aquatic species have demonstrated potential in regulating the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a sophisticated assemblage present in immune cells responsible for detecting and responding to external mediators. The NLRP3 inflammasome plays a role in several pathological conditions such as type 2 diabetes, hyperglycemia, Alzheimer's disease, obesity, autoimmune disorders, and cardiovascular disorders. Venom peptides derived from animal venoms have been discovered to selectively induce certain signalling pathways, such as the NLRP3 inflammasome, mitogen-activated protein kinase (MAPK), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Experimental evidence has demonstrated that venom peptides can regulate the expression and activation of the NLRP3 inflammasome, resulting in the secretion of pro-inflammatory cytokines including interleukin (IL)-1β and IL-18. Furthermore, these peptides have been discovered to impede the activation of the NLRP3 inflammasome, therefore diminishing inflammation and tissue injury. The functional properties of venom proteins and peptides obtained from snakes, bees, wasps, and scorpions have been thoroughly investigated, specifically targeting the NLRP3 inflammasome pathway, venom proteins and peptides have shown promise as therapeutic agents for the treatment of certain inflammatory disorders. This review discusses the pathophysiology of NLRP3 inflammasome in the onset of various diseases, role of venom as therapeutics. Further, various venom components and their role in the modulation of NLRP3 inflammasome are discoursed. A substantial number of venomous animals and their toxins are yet unexplored, and to comprehensively grasp the mechanisms of action of them and their potential as therapeutic agents, additional research is required which can lead to the development of novel therapeutics.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β plaques and tau tangles, leading to cognitive decline and dementia. Insulin-like Growth Factor-1 (IGF-1) is similar in structure to insulin and is crucial for cell growth, differentiation, and regulating oxidative stress, synaptic plasticity, and mitochondrial function. IGF-1 exerts its physiological effects by binding to the IGF-1 receptor (IGF-1R) and activating PI3K/Akt pathway. In addition to the physiological activities in the brain, numerous studies point to a potential protective role of the IGF-1 pathway in the pathogenesis of neurodegenerative diseases, such as AD. Interestingly, patients with AD often exhibit altered insulin and IGF-1 levels, along with an inadequate insulin response. Dysregulation of IGF-1 signaling contributes to hyperphosphorylation of tau, NFT accumulation, increased β- and γ-secretase activity, elevated Aβ production, and impaired Aβ clearance, highlighting the need to explore the role of this signaling for potential therapeutic targets of AD. This review explores the role of IGF signaling in AD pathology, highlighting IGF-1 as a promising therapeutic target due to its significant involvement in disease mechanisms. Modulating IGF-1 activity could help mitigate neurodegeneration and preserve cognitive function in AD. A comprehensive understanding of the mechanisms underlying IGF-1 dysregulation is crucial for developing targeted therapeutic strategies to address the complex and multifaceted nature of AD.

Parkinson's disease (PD), a common neurodegenerative disorder, is characterized by progressive loss of dopaminergic neurons, and accumulation of α-synuclein in the substantial nigra. Emerging evidence identifies ferroptosis as a regulated iron-dependent cell death mechanism marked by excessive lipid peroxidation (LPO) as a key contributor to PD pathogenesis. Ferroptosis is intertwined with critical disease processes such as aggregation of α-synuclein protein, oxidative stress generation, mitochondrial alteration, iron homeostasis dysregulation, and neuroinflammation. This mechanism disrupts cellular homeostasis by impairing iron metabolism and antioxidant pathways like the xc^-/glutathione/GPX4 axis and the CoQ10 pathway. This review consolidates current advancements in understanding ferroptosis in these mechanisms, increasing interest in contribution to PD pathology. In addition, it explores the latest developments in ferroptosis-targeting pharmacological agents, including their application in the preclinical and clinical study, and highlights their potential to revolutionize PD management. Unraveling the interplay between ferroptosis and PD offers a transformative perspective, paving the way for innovative therapies to combat this debilitating disease condition.

Progesterone plays a crucial and indispensable role in regulating immunity and attenuating inflammation. Nestorone^® (NES, segesterone acetate) is a steroidal progestin and a 19-norprogesterone derivative with no -CH₃ group radical at the 6-position. Here, we showed that NES enhanced the viability of lipopolysaccharide (LPS)-stimulated THP-1 cell-derived macrophages, potently inhibiting both arms of the Toll-like receptor 4 (TLR-4) signaling cascade triggered by LPS, especially the TLR-4/MyD88/NF-κB pathway. In addition, NES exerted an anti-inflammatory effect by significantly decreasing the secretion of inflammatory cytokines and chemokines in type II alveolar epithelial A549 cells and THP-1 cell-derived macrophages stimulated by LPS. Furthermore, we evaluated the potential of NES pre-treatment, administered 2 h prior to LPS exposure, to mitigate acute lung injury induced by LPS, using an LPS-induced acute lung injury (ALI) mouse model. In this study, NES alleviated lung inflammation and damage by reducing leukocyte infiltration and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) and lung tissues of mice. Interestingly, our findings indicate that NES at a dosage of 1 mg/kg (91.67%) was more effective than at dosages of 0.1 mg/kg (70.83%) or 10 mg/kg (87.50%), as well as more effective than dexamethasone (DEX, 5 mg/kg, 83.34%), in extending survival in mice subjected to lethal LPS-induced injury. Additionally, this dosage was more successful in reducing acute lung inflammation and alleviating diffuse alveolar damage in the lungs of C57 mice. Our study indicates that concentration is a critical determinant of the anti-inflammatory efficacy of NES. Consequently, NES emerges as a potentially promising therapeutic agent for the treatment of pulmonary inflammatory conditions through the modulation of TLR-4 signaling pathways.

Perindopril Erbumine is a widely used angiotensin-converting enzyme (ACE) inhibitor for managing hypertension and cardiovascular diseases. Its dual action of lowering blood pressure and mitigating inflammation makes it a cornerstone treatment in these conditions. However, its oral administration often results in suboptimal bioavailability and gastrointestinal side effects. This study aimed to develop and characterize a dissolving microneedle (dMN) patch for the transdermal delivery of Perindopril Erbumine to enhance therapeutic efficacy and patient compliance. A Perindopril Erbumine-loaded microneedle patch was fabricated using chitosan and polyvinyl alcohol (PVA) using the solvent casting method. The microneedle patch was evaluated for physical properties, mechanical strength, drug loading, and moisture content. Ex-vivo permeation through rat skin and in-vivo pharmacokinetic studies in rabbits was conducted to compare its performance with a marketed oral Perindopril Erbumine formulation. The developed patch demonstrated effective skin penetration, controlled drug release, and a six-fold enhancement in cumulative drug permeation (82.45% ± 1.54) compared to the oral solution (14.32% ± 1.60). The pharmacokinetic study revealed prolonged drug release, with a 7.9-fold increase in half-life (7.739 ± 0.243 h vs. 0.986 ± 0.93 h) and a significantly higher area under the curve (AUC) for the microneedle patch. Skin irritation studies confirmed the biocompatibility of the formulation, with no significant adverse effects observed. These findings highlight the potential of Perindopril Erbumine-loaded dissolving microneedles as a promising transdermal delivery system for improved therapeutic outcomes in managing hypertension and inflammation-related vascular conditions, potentially reducing inflammation through enhanced and targeted drug delivery.

Dengue, a formidable life-threatening malady, currently exerts a profound impact upon the Western Pacific and Southeast-Asian developing and underdeveloped nations. The intricacies inherent in addressing dengue are manifold, requiring a concerted effort not only towards vector control but also the implementation of efficacious host treatments to forestall the progression of the disease into severe manifestations, such as hemorrhage and shock. The only vaccine available for dengue in the market is DENGVAXIA, with several other vaccine candidates which are currently in the clinical developmental stages. However, DENGVAXIA, owing to incidences of adverse events in among children, was withdrawn in Philippines. This warrants the development of new safer vaccine candidates. The existent control strategies, regrettably, demonstrate inadequacy in effectively mitigating the rampant dissemination of this ailment. Moreover, the diagnostic and therapeutic modalities exhibit potential for refinement, specifically through precision diagnostics and tailored therapeutic interventions, to enhance the precision and efficacy of dengue management. This comprehensive review endeavors to provide an in-depth elucidation of the utilization of nanotechnology-based approaches synergistically integrated with conventional methodologies in the overarching domains of dengue control, diagnosis, and treatment.