Том 30, № 26 (2024)

:The rising interest in hydrogels nowadays is due to their usefulness in physiological conditions as multi-stimuli-responsive hydrogels. To reply to the prearranged stimuli, including chemical triggers, light, magnetic field, electric field, ionic strength, temperature, pH, and glucose levels, dual/multi-stimuli-sensitive gels/hydrogels display controllable variations in mechanical characteristics and swelling. Recent attention has focused on injectable hydrogel-based drug delivery systems (DDS) because of its promise to offer regulated, controlled, and targeted medication release to the tumor site. These technologies have great potential to improve treatment outcomes and lessen side effects from prolonged chemotherapy exposure.

Background:Hypoxic Pulmonary Hypertension (HPH), a prevalent disease in highland areas, is a crucial factor in various complex highland diseases with high mortality rates. Zhishi-Xiebai-Guizhi Decoction (ZXGD), traditional Chinese medicine with a long history of use in treating heart and lung diseases, lacks a clear understanding of its pharmacological mechanism.

Objective:This study aimed to investigate the pharmacological effects and mechanisms of ZXGD on HPH.

Methods:We conducted a network pharmacological prediction analysis and molecular docking to predict the effects, which were verified through in vivo experiments.

Results:Network pharmacological analysis revealed 51 active compounds of ZXGD and 701 corresponding target genes. Additionally, there are 2,116 targets for HPH, 311 drug-disease co-targets, and 17 core-targets. GO functional annotation analysis revealed that the core targets primarily participate in biological processes such as apoptosis and cellular response to hypoxia. Furthermore, KEGG pathway enrichment analysis demonstrated that the core targets are involved in several pathways, including the phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway and Hypoxia Inducible Factor 1 (HIF1) signaling pathway. In vivo experiments, the continuous administration of ZXGD demonstrated a significant improvement in pulmonary artery pressure, right heart function, pulmonary vascular remodeling, and pulmonary vascular fibrosis in HPH rats. Furthermore, ZXGD was found to inhibit the expression of PI3K, Akt, and HIF1α proteins in rat lung tissue.

Conclusion:In summary, this study confirmed the beneficial effects and mechanism of ZXGD on HPH through a combination of network pharmacology and in vivo experiments. These findings provided a new insight for further research on HPH in the field of traditional Chinese medicine.

Background:At present, drug development for treating Alzheimer’s disease (AD) is still highly challenging. Eriodictyol (ERD) has shown great potential in treating AD, but its molecular mechanism is unknown.

Objective:We aimed to explore the potential targets and mechanisms of ERD in the treatment of AD through network pharmacology, molecular docking, and molecular dynamics simulations.

Methods:ERD-related targets were predicted based on the CTD, SEA, PharmMapper, Swiss TargetPrediction, and ETCM databases, and AD-related targets were predicted through the TTD, OMIM, DrugBank, GeneCards, Disgenet, and PharmGKB databases. Protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomics analyses (KEGG) were used to analyse the potential targets and key pathways of the anti-AD effect of ERD. Subsequently, potential DEGs affected by AD were analysed using the AlzData database, and their relationships with ERD were evaluated through molecular docking and molecular dynamics simulations.

Results:A total of 198 ERD-related targets, 3716 AD-related targets, and 122 intersecting targets were identified. GO annotation analysis revealed 1497 biological processes, 78 cellular components, and 132 molecular functions of 15 core targets. KEGG enrichment analysis identified 168 signalling pathways. We ultimately identified 9 DEGs associated with AD through analysis of the AlzData data. Molecular docking results showed good affinity between the selected targets and ERD, with PTGS2, HSP90AA1, and BCL2. The interactions were confirmed by molecular dynamics simulations.

Conclusion:ERD exerts anti-AD effects through multiple targets, pathways, and levels, providing a theoretical foundation and valuable reference for the development of ERD as a natural anti-AD drug.