Recent Advances in Inflammation & Allergy Drug Discovery最新文献

Background: Andrographolide (AP), a bioactive anti-inflammatory compound of Sambiloto, inhibits NF-κB, TNF-α, and interleukin IL-6. Nowadays, molecular docking simulation between AP and dexamethasone against NF-κB receptor presented the energy AP higher than dexamethasone. This becomes a potential treatment for psoriasis.

Objective: This manuscript reported the effectiveness of AP from Sambiloto in treating psoriasis compared to topical steroids.

Methods: This study conducted TLC analysis of AP content and its metabolite impurities, emulgel formulation, molecular docking, in-silico skin toxicity study, and in-vivo anti-psoriatic activity. This was a combination study of an in-silico study and an in-vivo study. This in-silico study was analyzed through multivariate statistical analysis (PCA) to elucidate the data constellation relationship of andrographolide derivatives with several target proteins. The intervention was performed in seven days. The PASI score, molecular parameters (IL-6, IL-17, VEGF, and TNF-a levels), and histopathological findings were assessed.

Results: Molecular docking results revealed andrographolide to exhibit a relatively high binding affinity towards IL-6, NF-kB, and TNF-α which is comparable to the corticosteroids, andrographolide also shares similar residue interaction profile with each of the respective protein's native ligand. In the in-vivo study, we found several parameters statistically significantly different regarding the intervention, including final PASI score (p = 0.017), redness (p = 0.017), scale (p = 0.040), thickness (p = 0.023), total histopathology of psoriasis score (p = 0.037), keratin layer score (p = 0.018).

Conclusion: Emulgel AP 0.1% could lower the anti-inflammatory agent, which is vital to psoriasis progression.

Psoriasis is an autoimmune systemic chronic inflammatory disease that exhibits characteristic detrimental effects on the skin, often leading to infections or comorbid conditions. The multifaceted nature of psoriasis has made it very challenging to treat, especially with current chemotherapy options. Therefore, it is essential to consider phytoconstituents as novel alternatives. However, despite demonstrating higher anti-inflammatory, anti-psoriasis, and immunomodulatory potential, their clinical usage is hindered due to their poor physicochemical properties. To address these drawbacks, nanoparticulate drug delivery systems have been developed, helping to achieve better permeation of phytoconstituents through topical administration. This has breathed new life into traditional systems of medicine, particularly in the context of treating psoriasis. In this current review, we present a detailed, comprehensive, and up-to-date analysis of the literature, which will contribute to affirming the clinical role of phyto-nano interventions against psoriasis.

Allergic illnesses occur when an organism's immune system is excessively responsive to certain antigens, such as those that are presented in the environment. Some people suffer from a wide range of immune system-related illnesses including allergic rhinitis, asthma, food allergies, hay fever, and even anaphylaxis. Immunotherapy and medications are frequently used to treat allergic disorders. The use of probiotics in bacteriotherapy has lately gained interest. Probiotics are essential to human health by modulating the gut microbiota in some ways. Due to probiotics' immunomodulatory properties present in the gut microbiota of all animals, including humans, these bacterial strains can prevent a wide variety of allergic disorders. Probiotic treatment helps allergy patients by decreasing inflammatory cytokines and enhancing intestinal permeability, which is important in the battle against allergy. By altering the balance of Th1 and Th2 immune responses in the intestinal mucosa, probiotics can heal allergic disorders. Numerous studies have shown a correlation between probiotics and a reduced risk of allergy disorders. A wide range of allergic disorders, including atopic dermatitis, asthma, allergic retinitis and food allergies has been proven to benefit from probiotic bacteria. Therefore, the use of probiotics in the treatment of allergic diseases offers a promising perspective. Considering that probiotic intervention in the treatment of diseases is a relatively new field of study, more studies in this regard seem necessary.

Flos Magnoliae is one of the important medicinal plants in different traditional medicine, including Chinese herbal medicine. Lignans and neolignans, including tetrahydrofurofuran, tetrahydrofuran, and aryltetralin, are present in the Flos Magnoliae species. A wide range of pharmacological activity of Flos Magnoliae has been reported in medicine. Fargesin has been isolated from Magnolia fargesii and it is a lignan-class phytochemical. Fargesin has numerous pharmacological activities in medicine, including its effectiveness on lipid and glucose metabolism, oxidative stress, myocardial apoptosis, etc. In the present work, we have summarized the detailed scientific information of fargesin concerning its medicinal properties and pharmacological activities. Numerous biological and chemical aspects of fargesin are discussed here, including the detailed pharmacological activities and analytical aspects of fargesin. In this review, we have also compiled analytical data on fargesin based on available scientific literature. Ethnopharmacological information on fargesin was gathered by a literature survey on PubMed, Science Direct, Google, and Scopus using the terms fargesin, Flos Magnoliae, phytochemical, and herbal medicine. The present review paper compiled the scientific data on fargesin in medicine for its pharmacological activities and analytical aspects in a very concise manner with proper citations. The present work signified the biological importance of fargesin in medicine due to its significant impact on bone disorders, lung injury, colon cancer, atherosclerosis, neurological disorders, ischemia, sars-cov-2, allergy, lipid and glucose metabolism, melanin synthesis, and different classes of enzymes. Furthermore, fargesin also has anti-inflammatory, antihypertensive, antiprotozoal, antimycobacterial, and antifeedant activity. However, analytical methods used for the separation, identification and isolation of fargesin in different biological and non-biological samples were also covered in the present review. The present work revealed the pharmacological activities and analytical aspects of fargesin in medicine and other allied health sectors.

Background: Cutaneous leishmaniasis (CL) is a parasitic disease with a significant burden in the Old World countries.

Objective: In the current study, some of the primary biochemical properties and IFN-γ inducing epitopes with specific binding capacity to human and mouse MHC alleles were predicted for Leishmania major gp46 antigenic protein.

Methods: Several online servers were used to predict physico-chemical traits, allergenicity, antigenicity, transmembrane domain and signal peptide, subcellular localization, post-translational modifications (PTMs), secondary and tertiary structures, tertiary model refining with validations. Also, IEDB web server was used to predict mouse/human cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes.

Results: The 33.25 kDa protein was stable, hydrophilic, antigenic, while non-allergenic, with enhanced thermotolerance and 45 PTM sites. The secondary structure encompassed a random coil, followed by extended strands and helices. Ramachandran-based analysis of the refined model showed 73.1%, 21.6%, 3.4% and 1.9% of residues in the most favored, additional allowed, generously-allowed and disallowed regions, respectively. Epitope screening demonstrated 4 HTL epitopes against seemingly protective HLA alleles, 5 HTL epitopes against the HLA reference set, 3 human CTL epitopes and a number of mouse MHC-restricted epitopes.

Conclusion: This paper provides insights into the bioinformatics characteristics of the L. major gp46 protein as a promising vaccine candidate.

A complicated biological reaction of vascular tissues to damaging stimuli like infections, harmed cells, or irritants is called inflammation. Symptoms include redness, inflamed joints, stiffness, discomfort in the joints, and loss of joint function. NSAIDs are frequently used to treat inflammation. Sadly, these drugs raise the possibility of blood clots, which can result in heart attacks and strokes. Consequently, there is ongoing research focusing on developing potent anti-inflammatory drugs using natural ingredients. Natural products, due to their diverse chemical composition, offer a rich source for the development of novel medications. The treatment of various inflammation- related disorders heavily relies on a natural substance derived from medicinal plants. The objective of the present study is to assemble information on potential parts of the plants or phytochemicals derived from medicinal plants used on inflammatory models, employing state-ofthe- art scientific methodologies. In this study, state-of-the-art scientific methodologies are utilized to investigate the effects of phytochemicals derived from medicinal plants. Relevant data is collected, focusing on the examination of these phytochemicals in experimental models of inflammation. The study aims to collect thorough data on potential plant parts or promising phytochemicals derived from medicinal plants that have been evaluated using advanced scientific techniques in the realm of inflammation models. This compilation will offer valuable insights into their potential as anti-inflammatory agents. The findings have the potential to contribute to the development of new and improved anti-inflammatory medications with fewer or no adverse effects compared to current treatments. While many of these studies hold academic interest only a few are accepted into clinical trials. Numerous phytoconstituents have been identified for exhibiting diverse pharmacological actions.

IgAN is the most common form of glomerulonephritis affecting 2000000 people annually. The disease ultimately progresses to chronic renal failure and ESRD. In this article, we focused on a comprehensive understanding of the pathogenesis of the disease and thus identifying different target proteins that could be essential in therapeutic approaches in the management of the disease. Aberrantly glycosylated IgA1 produced by the suppression of the enzyme β-1, 3 galactosyltransferase ultimately triggered the formation of IgG autoantibodies which form complexes with Gd-IgA1. The complex gets circulated through the blood vessels through monocytes and ultimately gets deposited in the glomerular mesangial cells via CD71 receptors present locally. This complex triggers the inflammatory pathways activating the alternate complement system, various types of T Cells, toll-like receptors, cytokines, and chemokines ultimately recruiting the phagocytic cells to eliminate the Gd-IgA complex. The inflammatory proteins cause severe mesangial and podocyte damage in the kidney which ultimately initiates the repair process following chronic inflammation by an important protein named TGFβ1. TGF β1 is an important protein produced during chronic inflammation mediating the repair process via various downstream transduction proteins and ultimately producing fibrotic proteins which help in the repair process but permanently damage the glomerular cells.

Non-steroidal anti-inflammatory drugs (NSAIDs) have a long history in the healthcare system due to their therapeutic potential. These NSAIDs cause ulcerogenicity, stomach pains, gastrointestinal hemorrhage, mucosa bleeding, and pancreatitis when used moderately and consistently. With researchers, managing the aforementioned adverse effects therapeutically is getting increasingly difficult. One method for creating NSAID moieties with low penetration as well as ulcerogenic properties is the prodrug technique. During the oral consumption of NSAID-prodrugs, ulcerations, intestinal hemorrhage, and mucosa hemorrhage have significantly decreased. Considering this background, this review focussed on NSAID prodrugs as well as their justifications, the pathogenesis of NSAIDs inducing gastrointestinal toxicity, and the role of different antioxidants and spacer groups. Prodrug moieties have more advantages over parent medicines concerning both solubility and lipophilicity. In general, NSAID-class prodrugs can successfully treat both acute and long-term inflammation and aches without causing ulcerotoxicity and related gastrointestinal side effects, which reduces their burden from the pharmacoeconomic perspective.

Background: The COVID-19 pandemic is a real global health crisis. Its clinical presentation has evolved over time with an increasing number of symptoms. Olfactory dysfunction (OD) has recently been recognized as a frequent symptom relevant to screening for COVID-19, especially in pauci-asymptomatic forms. However, the underlying mechanisms of OD are not yet fully understood.

Aim: To determine the prevalence of OD in healthcare workers with SARS-CoV-2 and to identify its associated factors.

Methods: This is a cross-sectional, analytical study, carried out during a period of six months and including all healthcare workers at Farhat Hached Academic Hospital (Tunisia) who were diagnosed with SARS-CoV-2 by PCR, RAT, or chest CT scan.

Results: A total of 474 healthcare workers were included, representing a participation rate of 85.4%. The mean age was 41.02±10.67 years with a sex ratio of 0.2. The distribution of this population by department noted that it was mainly maternity (13.9%). The most presented workstation was nursing (31.4%). OD represented 39.2% of the reasons for consultation. Hospitalization was indicated in 16 patients (3.4%). The average duration of hospitalization was 8.87 ± 7.8 days. The average time off work was 17.04 ± 11.6 days. OD persisted for more than 90 days in 35 patients (7.4%). After multiple binary logistic regression, OD was statistically associated with female gender (p =0.001; OR 95% CI: 2.46 [1.4-4.2]) and blue-collar occupational category (p =0.002; OR IC95%:3.1 [1.5-6.5]). A significant association was also noted between OD and professional seniority and absence from work duration (p =0.019; OR 95% CI: 0.97 [0.95-0.99] and p =0.03; OR 95% CI: 0.97 [0.95-0.99]) respectively.

Conclusion: OD is common in COVID-19 patients. The identification of its associated factors may contribute to enhancing the understanding of its mechanism and drive therapeutic options.

Background: Antibacterial and antimalarial drugs play a critical role in combating infectious diseases. It is a continuous work to develop new types of antibacterial and antimalarial drugs.

Objective: To better understand current landscape and association of antibacterial and antimalarial agents, the European patent analysis was performed.

Methods: Antibacterial and antimalarial agents were analyzed by patent analysis. Patent documents from January 2003 to May 2022 were retrieved and analyzed.

Results: The present study indicated there were virtually three therapeutic approaches for antibacterial agents, including chemical drugs, biological products and siRNA technology. Chemical drugs were a mainstream therapeutic approach for development of both antibacterial and antimalarial agents. However, the present study found that in contrast to antimalarials, siRNA technology had been initially explored as therapeutic strategy for antibacterial agents. Also, our study is the first to show that there is a low correlation between antibacterial and antimalarial agents.

Conclusion: Globally, our study is the first one to show that it may be not a fast approach to discover antimalarial drugs from antibacterial agents based on drug repurposing. siRNA technology as therapeutic strategy had been explored and used in antibacterial field.