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  5. Volume 30, Issue 36, 2024

Current Pharmaceutical Design - Volume 30, Issue 36, 2024

Volume 30, Issue 36

Volume 30, Issue 36, 2024

  • Medicine, Immunology, Inflammation & Allergy, Pharmacology

      • An Update on Colistin in Clinical Healthcare Unit in the Kingdom of Saudi Arabia: A Narrative Review

        https://doi.org/10.2174/0113816128303422240723091231

        Globally, gram-negative bacteria are a significant cause of morbidity. Multi-drug resistance bacteria are responsible for an increasing surge in infections that place a high cost on healthcare systems around the world. Recently, colistin, an antibiotic belonging to the polymyxin family, was reintroduced to combat multi- drug-resistant gram-negative bacteria. Excessive and persistent use of colistin has led to the development and spread of colistin-resistant gram-negative bacteria throughout the globe. Healthcare units in various countries, including Saudi Arabia, are currently battling colistin-resistant gram-negative bacteria. Recently, colistin-resistant gram-negative bacteria have become a major health concern in Saudi Arabia. Hence, extensive epidemiological surveys and studies are required to understand the current status of the colistin antibiotic. Examining the knowledge currently available to the medical community on the molecular mechanism, clinical effectiveness, molecular epidemiology, and bacterial resistance to colistin in Saudi Arabia is the aim of this review.

    • Bioactive Compounds in Species with Potential for the Treatment of Chronic Venous Disease: A Review

      https://doi.org/10.2174/0113816128314974240724045220

      Chronic venous disease (CVD) significantly impacts global health, presenting a complex challenge in medical management. Despite its prevalence and the burden it places on healthcare systems, CVD remains underdiagnosed and undertreated. This review aims to provide a comprehensive analysis of the bioactive compounds in the genus, exploring their therapeutic potential in CVD treatment and addressing the gap in current treatment modalities. A narrative review methodology was adopted, focusing on the pharmacological effects of -derived bioactive compounds, including flavonoids and terpenes. Additionally, the review introduced the DBsimilarity method for analyzing the chemical space and structural similarities among compounds. The review highlights the genus as a rich source of pharmacologically active compounds, notably flavonoids and terpenes, which exhibit significant anti-inflammatory, antioxidant, and veno-protective properties. Some of these compounds have been integrated into existing therapies, underscoring their potential for CVD management. The DBsimilarity analysis further identified many clusters of compounds with more than 85% structural similarity. -derived bioactive compounds offer promising therapeutic potential for managing CVD, showcasing significant anti-inflammatory, antioxidant, and veno-protective effects. The need for further comparative studies, as well as safety and efficacy investigations specific to CVD treatment, is evident. This review underlines the importance of advancing our understanding of these natural compounds and encouraging the development of novel treatments and formulations for effective CVD management. The DBsimilarity method's introduction provides a novel approach to exploring the chemical diversity within the genus, opening new pathways for pharmacological research.

    • Cisplatin-based Liposomal Nanocarriers for Drug Delivery in Lung Cancer Therapy: Recent Progress and Future Outlooks

      https://doi.org/10.2174/0113816128304923240704113319

      In order to improve the treatment of lung cancer, this paper looks at the development of cisplatin-based liposomal nanocarriers. It focuses on addressing the drawbacks of conventional cisplatin therapy, including systemic toxicity, inadequate tumor targeting, and drug resistance. Liposomes, or spherical lipid vesicles, offer a potentially effective way to encapsulate cisplatin, enhancing its transport and minimizing harmful effects on healthy tissues. The article discusses many liposomal cisplatin formulations, including pH-sensitive liposomes, sterically stabilized liposomes, and liposomes coupled with specific ligands like EGFR antibodies. These novel formulations show promise in reducing cisplatin resistance, optimizing pharmacokinetics, and boosting therapeutic results in the two and models. They also take advantage of the enhanced permeability and retention (EPR) effect in the direction of improved tumor accumulation. The study highlights the need for more investigation to move these liposomal formulations from experimental to clinical settings, highlighting their potential to offer less harmful and more effective cancer therapy alternatives.

    • Identification of Peptidoglycan Glycosyltransferase FtsI as a Potential Drug Target against and Serovars through Subtractive Genomics, Molecular Docking and Molecular Dynamics Simulation Approaches

      https://doi.org/10.2174/0113816128332400240827061932
      Introduction

      serovar Enteritidis and serovar Typhimurium are among the main causative agents of nontyphoidal infections, imposing a significant global health burden. The emergence of antibiotic resistance in these pathogens underscores the need for innovative therapeutic strategies.

      Objective

      To identify proteins as potential drug targets against and serovars using approaches.

      Methods

      In this study, a subtractive genomics approach was employed to identify potential drug targets. The whole proteome of PT4 and (D23580), containing 393 and 478 proteins, respectively, was analyzed through subtractive genomics to identify human homologous proteins of the pathogen and also the proteins linked to shared metabolic pathways of pathogen and its host.

      Results

      Subsequent analysis revealed 19 common essential proteins shared by both strains. To ensure host-specificity, we identified 10 non-homologous proteins absent in humans. Among these proteins, peptidoglycan glycosyltransferase FtsI was pivotal, participating in pathogen-specific pathways and making it a promising drug target. Molecular docking highlighted two potential compounds, Balsamenonon A and 3,3',4',7-Tetrahydroxyflavylium, with strong binding affinities with FtsI. A 100 ns molecular dynamics simulation having 10,000 frames substantiated the strong binding affinity and demonstrated the enduring stability of the predicted compounds at the docked site.

      Conclusion

      The findings in this study provide the foundation for drug development strategies against infections, which can contribute to the prospective development of natural and cost-effective drugs targeting and .

    • Active Ingredients and Mechanism of Gegen Qinlian Decoction in the Treatment of Diabetic Cardiomyopathy: A Network Pharmacology Study

      https://doi.org/10.2174/0113816128312242240722080551
      Background

      Diabetic cardiomyopathy (DCM) is a common diabetes complication with limited medications. Gegen Qinlian decoction (GQD) has been used in the treatment of diabetes and its related complications in China for several decades.

      Objective

      In this study, network pharmacology was employed to predict the active ingredients, key targets, and pathways involved in the treatment of DCM by GQD and to validate it by animal experiments.

      Methods

      The active ingredients of GQD were retrieved from TCMSP and published literature. DCM-related gene targets were searched in Drugbank, Genecards, Disgenet, and OMIM disease databases. Protein-protein interaction networks were constructed using the STRING database and Cytoscape. GO analysis and KEGG pathway enrichment analysis were performed using the Metascape platform. Moreover, a diabetic mouse model was established to evaluate the therapeutic effects of GQD by measuring serum biochemical markers and inflammation levels. Finally, the expression of predicted key target genes was determined using real-time quantitative PCR.

      Results

      A total of 129 active ingredients were screened from GQD. Moreover, 146 intersecting genes related to DCM were obtained, with key targets, including AKT1, TNF, IL6, and VEGFA. Lipid and atherosclerosis, AGE-RAGE, PI3K-AKT, and MAPK pathways were identified. Blood glucose control, decreased inflammatory factors, and serum CK-MB levels were restored after GQD intervention, and the same occurred with the expressions of PPAR-γ, AKT1, APOB, and GSK3B genes.

      Conclusion

      Quercetin, kaempferol, wogonin, 7-methoxy-2-methyl isoflavone, and formononetin may exert major therapeutic effects by regulating key factors, such as AKT1, APOB, and GSK3B, in the inflammatory reaction, glycolipid oxidation, and glycogen synthesis related signaling pathways.

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