Drugs Drug Candidates, Volume 4, Issue 4 (December 2025) – 3 articles

Background/Objectives: This study investigated the flavonoid enrichment and antimicrobial activity of the ethyl acetate fraction (EAF) obtained from Croton blanchetianus (Euphorbiaceae) leaves against Staphylococcus aureus, including the methicillin-resistant strains (MRSA) that were isolated, as well as its possible mechanism of action. Methods: Croton blanchetianus leaves were extracted with ethanol:water (50%), then the extract was spray-dried and partitioned (8×) with ethyl acetate. Phytochemical analysis was performed using thin layer chromatography (TLC), while antibacterial activity was conducted using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods. Results: Chemical profiling (TLC) confirmed multiple flavonoid bands and the presence of hyperoside; the total flavonoid content in the EAF reached 25.3% (≈2.28× the spray-dried extract and 6.65× the aqueous fraction). The MIC and MBC assays against S. aureus ATCC 29213 and six clinical isolates showed an MIC of 4–32 μg/mL and an MBC of 16–64 μg/mL for EAF. The combination of EAF with chloramphenicol showed a complete synergistic effect for S. aureus ATCC 29213 and S. aureus UFPEDA 705, a partial effect for S. aureus UFPEDA-659 and S. aureus UFPEDA-671, antagonistic effect for S. aureus UFPEDA 731 and S. aureus UFPEDA 802, and no effect for S. aureus UFPEDA-691. Growth curves indicated time- and concentration-dependent inhibition. Membrane integrity assays revealed K⁺ efflux and release of DNA/RNA and proteins, suggesting bacterial membrane destabilization as a likely mechanism. Conclusions: The flavonoid-rich fraction of C. blanchetianus exhibits potent anti-S. aureus activity, including MRSA. Furthermore, it was observed that EAF has a synergistic effect with chloramphenicol and acts through membrane damage, making it a candidate for a phytoderived adjuvant in antimicrobial therapies. Full article

Background/Objectives: Natural products, especially plant metabolites, play a crucial role in drug development and are widely used in medicine, cosmetics, and nutrition. The present review aims to provide a comprehensive overview of the pharmacological profile of Glycyrrhizin (GL), with a specific focus on its molecular targets. Methods: Scientific literature was thoroughly retrieved from reputable databases, including Scopus, Web of Science, and PubMed, up to 30 July 2025. The keywords “glycyrrhizin” and “glycyrrhizic acid” were used to identify relevant references, with a focus on pharmacological applications. Studies on synthetic analogs, non-English publications, non-pharmacological applications, and GL containing crude extracts were largely excluded. Results: Glycyrrhizin, the major bioactive constituent of Glycyrrhiza glabra, exhibits diverse pharmacological activities, including anti-inflammatory, antiviral, hepatoprotective, antitumor, neuroprotective, and immunomodulatory effects. These actions are primarily mediated through the inhibition of high-mobility group box 1 (HMGB1) and the modulation of key signaling pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and various cytokine networks. As a result of its therapeutic potential, GL-based formulations, including Stronger Neo-Minophagen C, and GL-rich extracts of G. glabra are commercially available as pharmaceutical preparations and food additives. Conclusions: Despite its therapeutic potential, the clinical application of GL is limited by poor oral bioavailability, metabolic variability, and adverse effects such as pseudoaldosteronism. Hence, careful consideration of pharmacokinetics and safety is essential for translating its therapeutic potential into clinical practice. Full article