Hinokiflavone

Erectile dysfunction (ED) is a significant health issue affecting the global male population, with a complex and multifaceted etiology. High-fat diet (HFD) is known to impair endothelial function and promote the development of ED. Hinokiflavone (HINO), a naturally occurring biflavonoid, has garnered attention for its notable antioxidant and anti-inflammatory activities, suggesting its potential therapeutic role in treating ED.

This study aims to investigate the therapeutic effects and underlying mechanisms of HINO in HFD-induced ED.

Network pharmacology and molecular dynamics simulation were employed to predict relevant targets and analyze their binding kinetics. Rat corpus cavernosum endothelial cells (RCCECs) were treated with palmitic acid in vitro to induce metabolic dysfunction. The ED model was established in vivo by feeding male rats an HFD (60 kcal% fat).

The primary outcomes were the target genes and pathways associated with HINO and the evaluation of its therapeutic potential in HFD-induced ED.

Bioinformatics analyses identified the epidermal growth factor receptor (EGFR) and protein kinase B (Akt) as key molecular targets of HINO. Treatment with HINO promoted RCCEC proliferation, enhanced antioxidant activities, and increased nitric oxide production. The administration of HINO ameliorated erectile dysfunction, improved serum lipid profiles, and reduced oxidative stress in HFD-fed rats. The protective effects of HINO against endothelial dysfunction and impaired cell viability were mediated through modulation of the EGFR/PI3K/Akt/eNOS signaling pathway.

The results provide a strong rationale for further investigation of HINO as a novel therapeutic agent for ED, with promising implications for future clinical applications.

In this study, we found that HINO could mitigate HFD-induced ED. Limitations of the study include that the alternative mechanisms of HINO were not fully explored in these settings.

Our findings underscore the pharmacological properties of HINO in the management of ED, particularly through the modulation of critical targets such as EGFR.

The penicillin-binding protein (PBP) 2a and beta-lactamase play important roles in the resistance of Staphylococcus aureus to beta-lactam antibiotics, making them vital targets for the discovery of new chem. entities.The vast South African medicinal plants (SAMP) with reported antibacterial properties have not been sufficiently explored to date.This study explored SAMP with reported antibacterial activities for putative leads against S. aureus PBP2a and beta-lactamase using computational studies.A total of 187 SAMPs with antibacterial activity were identified, spanning 67 families, with Fabaceae (18), Asteraceae (19), and Lamiaceae (11) being the most prominently represented.A library of 4230 secondary metabolites (SM), predominantly identified from leaves of the plants, was constructed and docked against active site of S. aureus PBP2a.The top-ranked SM were further docked to the allosteric site of S. aureus PBP2a, beta-lactamase and their ensembles obtained from conformational clustering and investigated for druggable pharmacokinetic and synthetic features.Thermodn. stability anal. of the resulting complexes of the leads over a 120-ns MD simulation period revealed astragalin 6′′-gallate (-62.11 ± 4.94 and -39.70 ± 4.91 kcal/mol) and 20(29)-Lupene-3β-Isoferulate (-55.66 ± 8.91 and -42.88 ± 5.93 kcal/mol) as the most potent against S. aureus PBP2a and beta-lactamase compared to reference standards, ceftaroline (-46.06 ± 5.65 kcal/mol) and clavulanate (-21.40 ± 4.77 kcal/mol), resp., with an allosteric modulatory effect on Tyr446, the active site gatekeeper residue in S. aureus PBP2a.Astragalin 6′′-gallate and 20(29)-lupene-3β-isoferulate, identified in Myrothamnus flabellifolia and Euclea natalensis, resp., are likely contributors to the reported antibacterial activity of these plants.The potential dual-target inhibitory properties and the ability to modulate the active site conformation of S. aureus PBP2a position these metabolites as promising candidates for further investigation in combating S. aureus infections.Efforts are underway in this direction.