Inflammopharmacology最新文献

The term "inflammatory bowel disease" (IBD) refers to a group of chronic inflammatory gastrointestinal disorders, which include ulcerative colitis and Crohn's disease. The necessity for alternative therapeutic approaches is underscored by the fact that although present medicines are successful, they frequently result in considerable adverse effects. Naturally occurring substances included in fruits and vegetables called polyphenols have been shown to have the capacity to control important inflammatory pathways including NF-κB and JAK/STAT, which are essential for the pathophysiology of IBD. The processes by which polyphenols, such as curcumin, EGCG, resveratrol, and quercetin, reduce inflammation are examined in this article. Polyphenols may have therapeutic advantages by blocking the synthesis of cytokines and the activation of immune cells by targeting these pathways. Preclinical study indicates a reduction in intestinal inflammation, which is encouraging. However, more clinical research is needed to determine the clinical relevance of polyphenols in the therapy of IBD, especially with regard to their long-term safety and bioavailability.

Rheumatoid Arthritis (RA) is an autoimmune, chronic, systemic inflammatory disease that causes redness, swelling, stiffness, and joint pain. It is a long-lasting disease that can have a widespread impact on the body, often affecting the hands, feet, and wrists. The immune cells, such as dendritic cells, T cells, B cells, macrophages, and neutrophils, play a significant role in bone degradation and inflammation. Several cytokines, including TNF-α and IL-17A, play a significant role in causing bone erosion, cartilage deterioration, and joint inflammation. Progesterone and estrogen have a crucial impact on the pathophysiology of RA, influencing the immune system. Research has demonstrated that hormone replacement therapy (HRT) can effectively reduce inflammation, improve disease activity, enhance joint health, alleviate pain, and promote bone strength. Treatments such as tamoxifen and raloxifene, known as selective estrogen receptor modulators (SERMs), are effective against chronic inflammatory illnesses like RA. The treatment with Gonadotropin-releasing hormone (GnRH) has an impact on the hypothalamic-pituitary-gonadal axis, which in turn affects the activity of RA illness. These alternative treatments hold promise in enhancing well-being and alleviating joint pain for individuals with RA.

Psoriasis represents a chronic autoimmune skin condition defined by various clinical forms, including inverse, erythrodermic, pustular, guttate, plaque types. While current therapies, including topical treatments but also systemic through conventional synthetic drugs and biologics, have improved symptom management, no treatment completely cures the disease, and numerous options are linked to considerable adverse effects, including immunosuppression and carcinogenic risks. Therefore, there is growing interest in bioactive compounds from natural sources due to their potential to reduce inflammation and oxidative stress in psoriasis with fewer adverse effects. The present narrative review aimed to address the limitations of current psoriasis therapies by exploring the therapeutic potential of bioactive compounds in the classes of flavonoids, terpenoids, omega-3 fatty acids, and alkaloids assessed through complex experimental models, focusing on their immunomodulatory and anti-inflammatory properties. Recent studies highlight the efficacy of natural bioactive compounds in reducing psoriasis symptoms, either as standalone treatments or in combination with conventional therapies. While these compounds show promise in alleviating psoriasis-related inflammation, further research is needed to optimize their therapeutic use, understand their mechanisms of action, and assess long-term safety. Future studies should focus on clinical trials to establish standardized protocols for incorporating bioactive compounds into psoriasis management and explore their potential role in personalized treatment strategies. Continued research is essential to develop more effective, safer, and affordable therapeutic options for psoriasis patients.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, severe, and potentially life-threatening skin and mucous membrane disorders. They are characterized by widespread skin and mucosal detachment and necrosis, and are classified based on the percentage of total body surface area (TBSA) affected. Given the severe and often life-threatening nature of these conditions, the identification and implementation of effective treatments is crucial. Notably, cyclosporin has demonstrated efficacy in managing these challenging conditions.

Methods: A systematic search was carried out through the PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases until May 2024. Additionally, a manual search was conducted through the reference lists of the included studies to minimize the risk of missing reports.

Results: Overall, 17 studies involving 4761 patients were included in our analysis. The majority of the included studies suggested favorable outcomes for the use of cyclosporin in SJS/TEN patients. The use of cyclosporin was associated with improved survival rates, early arrest of disease progression, faster re-epithelialization, reduced length of hospital stays, and lower rates of multi-organ failure. However, a few studies did not find a survival advantage with cyclosporin and even reported an increased risk of mortality, as well as an increased TBSA detachment and risk of infection.

Conclusion: Most studies indicate positive outcomes with cyclosporin treatment in SJS/TEN patients. This is likely due to cyclosporin's immunomodulatory properties, which may help attenuate the severe inflammatory response associated with these conditions.

Background: Osteoarthritis (OA) is a common age-related disease that causes pain and impaired mobility. Various blood metabolites are reportedly associated with bone health; however, their impact on OA remains unclear. Therefore, we conducted a metabolome-wide Mendelian randomization (MR) study to identify causal metabolites and therapeutic targets in OA.

Methods: Genetic associations of metabolites were derived from the largest genome-wide association study (GWAS) of the blood metabolome, which provided summary-level data on 1091 blood metabolites. Genetic associations with OA were obtained from four large-scale GWAS: McDonald's study (140,025 cases, 344,349 controls), Zengini's study (12,658 cases, 50,898 controls), Dönertaş's study (39,515 cases, 445,083 controls), and Tachmazidou's study (39,427 cases, 378,169 controls). MR and colocalization analyses were performed to validate the causal roles of the candidate metabolites. Further analyses were conducted using expression quantitative trait locus-based MR, single-cell sequencing data, protein-protein interaction networks, and druggability assessments. These analyses aimed to identify the differentially expressed genes and prioritize them as potential therapeutic targets.

Results: The genetically predicted levels of 10 metabolites were associated with OA. Elevated levels of five metabolites and reduced levels of another five metabolites were associated with an increased OA risk. Among these, five metabolites were prioritized based on the most compelling evidence. Seven genes were identified as potentially involved and could serve as novel therapeutic targets for OA.

Conclusion: Several blood metabolites were associated with OA, providing new insights into the etiology of OA and highlighting promising therapeutic targets.

Our study focused on a mouse model of obesity induced by a high-fat diet (HFD). We administered Semaglutide intraperitoneally (Ozempic ®-0.05 mg/Kg-translational dose) every seven days for six weeks. HFD-fed mice had higher blood glucose, lipid profile, and insulin resistance. Moreover, mice fed HFD showed high gut levels of TLR4, NF-kB, TNF-α, IL-1β, and nitrotyrosine and low levels of occludin, indicating intestinal inflammation and permeability, culminating in higher serum levels of IL-1β and LPS. Treatment with semaglutide counteracted the dyslipidemia and insulin resistance, reducing gut and serum inflammatory markers. Structural changes in gut microbiome were determined by 16S rRNA sequencing. Semaglutide reduced the relative abundance of Firmicutes and augmented that of Bacteroidetes. Meanwhile, semaglutide dramatically changed the overall composition and promoted the growth of acetate-producing bacteria (Bacteroides acidifaciens and Blautia coccoides), increasing hypothalamic acetate levels. Semaglutide intervention increased the number of hypothalamic GLP-1R+ neurons that mediate endogenous action on feeding and energy. In addition, semaglutide treatment reversed the hypothalamic neuroinflammation HDF-induced decreasing TLR4/MyD88/NF-κB signaling and JNK and AMPK levels, improving the hypothalamic insulin resistance. Also, semaglutide modulated the intestinal microbiota, promoting the growth of acetate-producing bacteria, inducing high levels of hypothalamic acetate, and increasing GPR43+ /POMC+ neurons. In the ARC, acetate activated the GPR43 and its downstream PI3K-Akt pathway, which activates POMC neurons by repressing the FoxO-1. Thus, among the multifactorial effectors of hypothalamic energy homeostasis, possibly higher levels of acetate derived from the intestinal microbiota contribute to reducing food intake.

Background: We aimed to examine the efficacy of intravenous vitamin C (IV-VC) in the treatment of hospitalized patients with moderate or severe COVID-19.

Method: We conducted a single-center and retrospective study including patients with COVID-19 diagnosis who were hospitalized. Patients were categorized into three groups as those who received low-dose (LDVC group, 2 g/day, n = 183) or high-dose IV-VC (HDVC group, 25 g/day, n = 41) and who did not receive IV-VC (control group, n = 46).

Results: 270 patients aged 19-97 years were enrolled. The median length of stay (LOS) was significantly high (9 days) in patients treated with high-dose VC when compared to patients treated with low-dose VC and control patients (6 vs 5 days, respectively). Need for intensive care unit (ICU) transfer was found to be significantly low in patients treated with low-dose VC (25.7%); contrarily, control patients had significantly higher rates of ICU transfer (67.4%), when compared to patients treated with high-dose VC (39%). Mortality of the LDVC group was significantly lower than that of the HDVC group (11.5 vs 29.3%). However, mortality rates were similar between the control and HDVC groups (21.7 vs 29.3%). According to the multivariate stepwise logistic regression mortality analysis, percent of change (∆%)-BUN was the most significant variable (p < 0.001), the second significant variable was ∆%-AST (p = 0.002), the third significant variable was respiratory distress (p = 0.002), and the fourth significant variable was the IV-VC groups (p = 0.017). The mortality risk of those in the LDVC group was 10.2 times low compared to the control group. Similarly, the risk of mortality in the HDVC group was 6.5 times lower than that of the control group.

Conclusion: Especially low and continious doses of IV-VC suggest fewer days of in-hospital LOS and survival benefit in hospitalized patients with moderate and severe COVID-19. Logistic regression analysis revealed that high-dose VC supplementation also had a mortality-reducing effect.

Nucleocytoplasmic translocation of HMGB1 (high mobility group box-1) plays a significant role in disease progression. Several methods contribute to the translocation of HMGB1 from the nucleus to the cytoplasm, including inflammasome activation, TNF-α signaling, CRM1-mediated transport, reactive oxygen species (ROS), JAK/STAT pathway, RIP3-mediated p53 involvement, XPO-1-mediated transport, and calcium-dependent mechanisms. Due to its diverse functions at various subcellular locations, HMGB1 has been identified as a crucial factor in several Central Nervous System (CNS) disorders, including Huntington's disease (HD), Parkinson's disease (PD), and Alzheimer's disease (AD). HMGB1 displays a wide array of roles in the extracellular environment as it interacts with several receptors, including CXCR4, TLR2, TLR4, TLR8, and RAGE, by engaging in these connections, HMGB1 can effectively regulate subsequent signaling pathways, hence exerting an impact on the progression of brain disorders through neuroinflammation. Therefore, focusing on treating neuroinflammation could offer a common therapeutic strategy for several disorders. The objective of the current literature is to demonstrate the pathological role of HMGB1 in various neurological disorders. This review also offers insights into numerous therapeutic targets that promise to advance multiple treatments intended to alleviate brain illnesses.

Acute pancreatitis is a potentially life-threatening inflammatory disorder of the exocrine pancreas characterized by early activation of pancreatic enzymes followed by macrophage-driven inflammation, and pancreatic acinar cell death. The most common causes are gallstones and excessive alcohol consumption. Inflammation and oxidative stress play critical roles in its pathogenesis. Despite increasing incidence, currently, no specific drug therapy is available to treat or prevent acute pancreatitis, in particular severe acute pancreatitis. New therapeutic agents are very much needed. Plant polyphenols have attracted extensive attention in the field of acute pancreatitis due to their diverse pharmacological properties. In this review, we discuss the potential of plant polyphenols in inhibiting the occurrence and development of acute pancreatitis via modulation of inflammation, oxidative stress, calcium overload, autophagy, and apoptosis, based on the currently available in vitro, in vivo animal and very few clinical human studies. We also outline the opportunities and challenges in the clinical translation of plant polyphenols for the treatment of the disease. We concluded that plant polyphenols have a potential therapeutic effect in the management and treatment of acute pancreatitis. Knowledge gained from this review will hopefully inspire new research ideas and directions for the development and application of plant polyphenols for treating this disease.

Cancer is the predominant and major cause of fatality worldwide, based on the different types of cancer. There is a limitation in the current treatment. So we need better therapeutic agents that counteract the progression and development of malignant tumours. Plant-derived products are closely related and useful for human health. Luteolin is a polyphenolic flavonoid bioactive molecule that is present in various herbs, vegetables, fruits, and flowers and exhibits chemoprotective and pharmacological activity against different malignancies. To offer innovative approaches for the management of various cancers, we present a comprehensive analysis of the latest discoveries on luteolin. The aim is to inspire novel concepts for the development of advanced pharmaceuticals targeting cancer and search specifically targeted reviews and research articles published from January 1999 to January 2024 that investigated the application of luteolin in various cancer management. A thorough literature search utilizing the keywords "luteolin" "Signalling Pathway" "cancer" and nanoparticles was performed in the databases of Google Scholar, Web of Science, SCOPUS, UGC care list and PubMed. Through the compilation of existing research, we have discovered that luteolin possesses several therapeutic actions against various cancer via a signaling pathway involving the of NF-κB regulation, AMPK/mTOR, toll-like receptor, Nrf-2, PI3K/Akt MAPK and Wnt/β-catenin and their underlying mechanism of action has been well understood. This review intended to completely integrate crucial information on natural sources, biosynthesis, pharmacokinetics, signaling pathways, chemoprotective and therapeutic properties against various cancers, and nanoformulation of luteolin.