Scientia Pharmaceutica

This review explores the pharmacological potential of chondroitin sulfate and fucoidan as immunomodulatory agents targeting N-acetylgalactosaminidase (nagalase) to normalize immune responses. Nagalase, an enzyme produced by tumor and virus-infected cells, contributes to immune suppression by deactivating macrophage-activating factor. Both chondroitin sulfate and fucoidan, as representatives of glycosaminoglycans and heteropolysaccharides, exhibit significant potential in inhibiting nagalase activity, thereby restoring immune functionality. Chondroitin sulfate, a key component of the extracellular matrix, demonstrates anti-inflammatory and tissue-regenerative properties by modulating nuclear factor (NF)-κB pathways and cytokine expression. Fucoidan, a sulfated polysaccharide derived from brown seaweed, enhances immune responses through macrophage and natural killer cell activation, while also exhibiting antiviral and anticancer activities. This dual action positions these compounds as promising agents for therapeutic interventions in chronic inflammatory conditions, cancer, and infectious diseases. The synergistic effects of chondroitin sulfate and fucoidan highlight their potential to address the root causes of immune dysregulation. This review aims to elucidate the underlying mechanisms of action and explore the clinical applications of these compounds within the framework of innovative immunotherapeutic strategies. However, current evidence is limited by the predominance of preclinical studies and variability in experimental models. Well-designed clinical trials are needed to validate their efficacy for therapeutic use.

We aimed to investigate the interaction mechanism of transport protein Human serum albumin (HSA) with a synthesized compound, QP-11, with tested antimalarial properties to monitor the changes in the protein because of QP-11 binding. The interaction between the antimalarial compound QP-11 and HSA was thoroughly investigated through a multidimensional approach, utilizing UV-VIS spectroscopy, fluorescence, time-resolved fluorescence, and CD (Circular dichroism), alongside molecular docking techniques. Our findings unveiled a robust 1:1 binding pattern, signifying a strong affinity between QP-11 and HSA. Employing static quenching, evidenced by time-resolved fluorescence spectroscopy, QP-11 was observed to induce fluorescence quenching of HSA, particularly binding to subdomain IIA. Thermodynamic parameters indicated that van der Waals forces and hydrogen bonding predominantly facilitated the binding, with increased temperature compromising complex stability. The 3D fluorescence and CD results demonstrated QP-11-induced conformational changes in HSA. Both experimental and in silico analyses suggested a spontaneous, exothermic binding reaction. The profound impact of the QP-11–HSA interaction underscores the potential for QP-11 in antimalarial drug development, encouraging further exploration for dose design and enhanced pharmacodynamic and pharmacokinetic properties.

This study aimed to characterize the chemical composition and evaluate the biological activities of the aerial parts of Alkanna corcyrensis Hayek (AC), an endemic Greek species not previously studied. Phytochemical analysis of the methanolic extract was performed using UHPLC-ESI-Q-TOF–MS/MS combined with molecular networking analysis. Additionally, the total phenolic content (TPC) and total flavonoid content (TFC) were determined. Chromatographic separations were carried out to isolate major compounds, and the antioxidant capacity, along with enzyme inhibitory activity, was assessed. The analysis led to the tentative identification of 86 compounds, including 67 phenolic compounds (mainly caffeic acid derivatives and flavonoid glycosides), 10 pyrrolizidine alkaloids of trachelanthamidine, platynecine, and retronecine types, and nine organic and fatty acid derivatives. Among these, one flavonol glycoside (kaempferol-O-malonyl methyl ester hexoside) and three pyrrolizidine alkaloids (9-sarracinoyl-trachelanthamidine/isoretronecanol, retronecine-pentoside, and trachelanthamidine/isoretronecanol-hexoside) were reported for the first time. The extract exhibited high TPC (74.45 mg GAE/g extract) and TFC (46.66 mg GAE/g extract). Chromatographic separations resulted in the isolation of five major metabolites, namely rosmarinic acid, danshensu, kaempferol-3-O-glucoside, kaempferol-3-O-galactoside, and quercetin-3-O-glycoside. Biological evaluation revealed considerable antioxidant activity and inhibitory effects against α-glucosidase (6.65 mmol ACAE/g extract). Overall, this study highlights the remarkable phytochemical diversity and richness of AC among alkanet species and demonstrates its promising antioxidant potential, laying the foundation for further investigations towards its future exploitation.