Abstract: Morus alba L., a member of the Moraceae family, is widely recognised for its medicinal and nutritional importance. Various extracts from Traditional Chinese, Ayurvedic, and Korean medicine systems are widely used, including tree leaves, fruits, root bark, and branches. This review critically summarises the pharmacological potential, phytochemical profile, and emerging therapeutic applications of Morus alba L. based on available preclinical and analytical studies. These activities are attributed to diverse bioactive constituents, including stilbenes, anthocyanins, phenolic acids, alkaloids, and flavonoids. Besides, the plant is important in sericulture and offers possible health advantages as a health supplement, herbal tea, jams, oils, and functional foods. This review compiles and evaluates extraction and analytical techniques used for the identification and characterisation of bioactive compounds from Morus alba. These include HPLC, GC-MS, NMR, ethanol-based extraction, hot water extraction, and advanced proteomic and metabolomic approaches. Chemometric tools, along with HPLC-DAD and UHPLC-ESI-MSn, are widely used for quality assessment and chemical standardisation. Recent studies in emerging areas such as molecular docking, ligand fishing, and nanoparticle-based systems further highlight its potential in drug discovery and delivery. Morus alba-mediated nanoparticles have also demonstrated antimicrobial, antioxidant, and drug delivery potential. This review highlights current evidence, identifies research gaps, and provides future directions for the development of Morus alba-based therapeutic and functional applications.
Introduction: The type III Phosphatidylinositol 4-kinase (PI4KIIIβ) serves as a key host factor that mediates the replication of RNA viruses and is involved in essential membrane trafficking events. The development of PI4KIIIβ-specific inhibitors could give insights into the enzyme's function and contribute to the treatment of viral diseases. However, the molecular features that determine inhibitor activity and selectivity remain unclear. Methods: PI4KIIIβ inhibitors with reported biological activities (pIC50) were systematically analyzed using machine-learning methods. Molecular characterization was performed using RDKit, Chemopy descriptors, and PubChem fingerprints. Multiple classification and regression models were developed and evaluated using 10-fold cross-validation to establish robust structureactivity relationships. results: It was suggested that the PubChem fingerprints-based linear regression, SMOreg, and GaussianProcesses models were more appropriate for the studied dataset to deliver the best predictive ability, which showed a correlation coefficient value > 0.7 in the 10-fold cross-validation. Results: It was suggested that the PubChem fingerprint-based linear regression, SMOreg, and GaussianProcesses models were more appropriate for the studied dataset to deliver the best predictive ability, which showed a correlation coefficient value > 0.7 in the 10-fold crossvalidation. PubChemFP389 and PubChemFP572, representing amidine-like fragments or guanidine- related motifs, and the aromatic amine fragment showed a negative correlation with respect to biological activity. Discussion: The study describes predictive models and provides insights into essential structural features in chemical compounds relevant for inhibitory activity, which could assist in the design and optimization of novel PI4KIIIβ inhibitors for antiviral and anticancer applications. A similar approach may be extended to a larger dataset of molecules or to other related drug targets. Conclusions: The findings suggest that excessive basicity and certain polar functionalities may be detrimental to PI4KIIIβ inhibition, providing important insights into the structural features influencing ligand binding and activity.
Introduction: Ellagic acid, Formononetin, and Glycitein are bioactive polyphenols possessing anticancer activity via apoptosis, cell cycle inhibition, and oncogenic signaling pathway modulation. In particular, Ellagic acid demonstrated interesting activity towards hepatocellular carcinoma (HCC), with the potential antiangiogenic target being VEGFR1. This study explores fluorinated Ellagic acid derivatives as potential VEGFR1 inhibitors, overcoming disadvantages of Formononetin/Glycitein co-drugs, namely poor ADME properties, hERG liability, and low bioavailability. Methods: Geometry optimization was carried out using DFT with the B3LYP/6-31G(d,p) basis set. Molecular docking with AutoDock Vina was applied in order to assess binding energies and inhibitory constants. Further MD simulation was conducted under physiological conditions using the OPLS 3.0 force field. Results: Ellagic acid established stable hydrogen-bond interactions with VEGFR1. Fluorination improved predicted binding affinity, inhibitory potency, and lipophilicity. Although the co-drugs exhibited stronger binding energies, they showed less favorable predicted ADMET profiles and increased toxicity alerts. All complexes remained highly stable during MD simulations (RMSD <1 Å). Discussion: Prioritization of fluorinated Ellagic acid was conducted according to favorable MM/GBSA binding energy, inhibitory constant, lipophilicity, oral bioavailability, and lack of predicted hERG-related cardiotoxicity. Formononetin and Glycitein demonstrated lower drug-likeness and predicted oral bioavailability and had cardiotoxicity issues. Conclusion: Fluorinated Ellagic acid derivatives could be considered as potential inhibitors of VEGFR1 due to their favorable binding characteristics and structural stability, along with predicted good ADMET properties without QikProp toxicity alerts.
Introduction: Atherosclerosis (AS) is a chronic inflammatory disease driven by disordered lipid metabolism and is a major cause of cardiovascular disease. 4′,7-Di-Omethylnaringenin (DMNG), a natural flavonoid derived from Zingiberaceae plants, has diverse biological activities, particularly anti-inflammatory and antioxidant effects. This study aimed to investigate the therapeutic effects of DMNG on AS and elucidate its underlying molecular mechanisms using proteomics. Methods: C57BL/6 mice fed a standard diet served as normal controls, whereas ApoE−/− mice fed a high-fat diet (HFD) were used as an AS model. ApoE−/− mice were treated with DMNG (25, 50, or 100 mg/kg/day) for 12 weeks. Body weight, serum lipid profiles, inflammatory cytokines, and oxidative stress markers were measured. Histopathological changes in the aorta were assessed using H&E and Masson's trichrome staining. Proteomic analysis was performed to identify key proteins and pathways, followed by validation using Western blotting. Results: DMNG treatment significantly reduced body weight gain and alleviated aortic intimal hyperplasia, plaque formation, and inflammatory infiltration while increasing collagen deposition. It improved lipid profiles by decreasing serum TC, TG, and LDL-C levels and increasing HDL-C levels. DMNG also reduced the serum levels of pro-inflammatory cytokines (IL-1β, IL- 6, and TNF-α), enhanced antioxidant enzyme activities (SOD and GSH-Px), and decreased MDA levels. Proteomic analysis identified ICAM1 as a protein downregulated by DMNG and implicated the MAPK/NF-κB pathway as the main regulatory axis. Western blotting confirmed that DMNG reduced the levels of ICAM1, p-p65, p-IκB, p-ERK, and p-p38. Discussion: These findings identify ICAM1 as a critical factor through which DMNG exerts its anti-atherosclerotic effects. By suppressing ICAM1 expression and the MAPK/NF-κB signaling pathway, DMNG alleviates vascular inflammation and oxidative stress, two core pathological processes in AS. Given the incomplete efficacy and adverse effects of current lipid-lowering therapies in some patients, DMNG, a natural flavonoid with multi-target activity, may represent a therapeutic candidate for managing AS, particularly its inflammatory components. Conclusion: DMNG ameliorates atherosclerosis by suppressing ICAM1 expression and MAPK/NF-κB signaling.
Introduction: Antimicrobial resistance, particularly when associated with biofilm formation, represents a major global health challenge. In this context, this study aimed to design, synthesize, and evaluate the in vitro biological activity of (E,E)-farnesylethane-1,2-diamine (4a) and (E,E)-farnesylpiperazine (4b), as dihydrochloride salts. Methodology: The compounds were synthesized following literature protocols. Their antibacterial activity was evaluated by determining Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) against Staphylococcus aureus (ATCC 25923), methicillinresistant S. aureus (HU25), and Escherichia coli (ATCC 25922). Biofilm formation was evaluated under subinhibitory conditions by quantifying biomass and viable cells. Experiments were conducted in triplicate and analyzed statistically. Biofilm morphology was examined using Scanning Electron Microscopy (SEM). Results: (E,E)-Farnesol exhibited activity against Gram-positive strains (MIC 64 μg/mL for ATCC 25923 and 32 μg/mL for HU25), with no bactericidal effect (MBC >512 μg/mL), indicating a bacteriostatic profile. In contrast, derivatives 4a and 4b displayed bactericidal activity against both Gram-positive and Gram-negative strains (MIC/MBC 32-64 μg/mL; MBC/MIC = 1). In biofilm assays, compound 4b reduced viable cell counts by over 90% across all strains (P < 0.001), while 4a showed moderate inhibition. SEM analysis confirmed reduced biofilm density and morphological alterations, particularly in Gram-positive bacteria. Discussion: Structural modification of (E,E)-farnesol significantly enhanced antibacterial and antibiofilm activity. Its derivatives demonstrate therapeutic potential against multidrug-resistant bacteria. Limitations include restriction to in vitro assays; further in vivo and cytotoxicity studies are needed. Conclusion: Compounds 4a and 4b emerge as promising candidates for further development, although additional in vivo and toxicity studies are required.
