Leptin and systemic lupus erythematosus: A comprehensive review

Leptin, a cytokine-like hormone produced by adipocytes, modulates innate and adaptive responses of the immune system. Several reports have indicated that leptin exerts pro-inflammatory effects which significantly trigger autoimmune responses in chronic inflammatory diseases e.g. systemic lupus erythematosus (SLE), an inflammatory, multi-system disease characterized by the presence of autoantibodies. Irrespective of contradictory results, many studies have indicated that leptin concentrations are increased in SLE patients. This might reflect genetic association, or a mechanism underlying the pathogenesis of SLE. To shed light on this possibility, recent studies investigated several polymorphism genes related to leptin in SLE patients from different ancestral groups. This review focuses on current understanding of the role of leptin in the pathogenesis of SLE and its immunomodulatory effects. This is expected to provide new leptin-based therapeutic interventions as modern approaches which are safer than the currently used ones for the treatment of SLE. Keywords: Leptin, Systemic Lupus Erythematosus, Polymorphism, Gene expressio

Targeting GSK-3β enzyme by diazepino-quinolone derivatives

Purpose: To synthesize a heterocyclic system containing quinolone and diazepine scaffolds as GSK-3β inhibitor. Methods: The diazepino-quinoline derivatives were synthesized starting from quinolone nucleus in a simple chemical reaction. The in vitro GSK-3β enzyme assay and MTT assay against cancer cell lines were carried out followed by Z´ı-LYTE GSK-3β assay. Anticancer activity was determined using U-87 glioma cell line. Results: Diazepino-quinoline derivatives were obtained in a good yield, and compound 102 exhibited significant activity against in vitro GSK-3β (IC50: 0.114 μM), and anticancer activity (IC50: 37 μM) against U-87 glioma cell line. Conclusion: The GSK-3β enzyme is a potential target to treat different diseases, and diazepines derivatives are a successful template for inhibitors design against GSK-3β enzyme with IC50 in a micromolar range

Molecular modelling studies and synthesis of novel quinoxaline derivatives with potential inhibitory effect on GSK-3β

Purpose: To synthesize quinoxaline derivatives and investigate their inhibitory effects on glycogen synthase kinase (GSK)-3β in vitro. Methods: Quinoxaline derivatives were synthesized via reaction between synthon 1 and DL- 2-amino succinic acid, and subsequent lactamization reaction. The new compounds were tested against GSK-3β in vitro to select the most potent compound which was then used for molecular modelling. Results: Novel quinoxaline derivatives with quinolone nucleus were successfully synthesized via simple chemical reactions. The compounds markedly inhibited GSK-3β, with compound 45 [3-(carboxymethyl)- 5-fluoro-10-(4-fluorophenyl)-2,7-dioxo-1,2,3,4,7,10-hexahydropyrido [2,3-f] quinoxaline-8-carboxylic acid] achieving the best effect (IC50 = 0.18 μM). The half maximal inhibitory concentrations (IC50) of the compounds were in micromolar range. Molecular modelling revealed several interactions between compound 45 and the binding site of GSK-3β. Conclusion: These results indicate that 3-(carboxymethyl)-5-fluoro-10-(4-fluorophenyl)-2,7-dioxo- 1,2,3,4,7,10-hexahydropyrido [2,3-f] quinoxaline-8-carboxylic acid is a potent inhibitor of GSK-3β and is thus a promising scaffold for the development of novel drugs that can effectively inhibit GSK-3β signaling pathway

Preparation and Characterization of Patch Loaded with Clarithromycin Nanovesicles for Transdermal Drug Delivery

Clarithromycin (CLR), categorized as a Biopharmaceutical Classification System class II drug, has several gastrointestinal tract side effects and an extremely unpalatable bitter taste. The current study aimed to design transdermal patch-embedded CLR niosomes to overcome the aforementioned CLR-related challenges. Various niosomal formulations were successfully fabricated and characterized for their morphology, size, in vitro release, and antimicrobial efficacy. Subsequently, the CLR niosomes were loaded into transdermal patches using the solvent casting method. The polydispersity index of the niosomes ranged from 0.005 to 0.360, indicating the uniformity of the niosomes. The encapsulating efficiency (EE)% varied from 12 to 86%. The optimal Chol: surfactant ratio for drug release was found to be 0.5:1. In addition, the encapsulation of CLR into niosomal nanovesicles did not reduce the antibacterial activity of the CLR. The niosomal patch had a significantly higher permeability coefficient of CLR than the conventional patch. In addition to that, a shear-thinning behavior was observed in the niosomal gels before loading them into a niosomal patch. The flux (Jss) of the niosomal patch was significantly higher than the conventional patch by more than 200 times. In conclusion, niosome-based transdermal patches could be a promising method for the transdermal drug delivery of class II drugs and drugs experiencing GIT side effects