Background and objective: Based on comprehensive network-pharmacology and molecular docking analysis, this study was intended to unveil the multiple mechanisms of Si-Ni-San (SNS) in treating anxious insomnia. Methods: The compounds of SNS were meticulously analyzed, selected and standardized with references to their pharmacological attributes. The components included chaihu (Bupleurum chinense DC.), baishao (Paeonia lactiflora Pall.), zhishi (Citrus aurantium L.) and gancao (Glycyrrhiza uralensis Fisch. ex DC.). We used the Traditional Chinese Medicine System Pharmacology (TCMSP) Database, Traditional Chinese Medicines Integrated Database (TCMID), GeneCards database, therapeutic target database (TTD) and comparative toxicogenomic database (CTD) to construct the components-compounds-targets networks and used Cytoscape 3.9.1 software to visualize the outcome. Afterwards, the STRING database and Cytoscape 3.9.1 software were utilized to construct and visualize the protein-protein interaction (PPI) network analysis. In addition, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were also conducted through the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The molecular docking program was carried out using AutoDock 4.2 software to understand interactions between target receptors and compound ligands selected for study. Results: We thoroughly sorted and filtered 31 pharmacologically active compounds from SNS. Subsequently, several potential target genes were predicted, of which there were 59 target genes distinctly associated with anxious insomnia. The PPI analysis indicated that the core target proteins included AKT1, IL6, TNF, SLC6A4, MAOA and GABRA2. The results of our study indicated that SNS potentially remediates anxious insomnia by reducing inflammation, neurodegeneration, and cell apoptosis of neurons. In addition, GO and KEGG enrichment analysis results indicated that SNS could modulate multiple aspects of anxious insomnia through mechanisms related to pathways of neuroactive ligand-receptor interaction. These pathways include various kinds of synaptic transmission pathways, and anti-inflammatory activity associated with response pathways. When we compared the components-compounds-targets networks and the compounds-targets-synaptic pathways networks, the five active compounds, including beta-Sitosterol, Kaempferol, Tetramethoxyluteolin, Isorhamnetin and Shinpterocarpin, were selected to conduct molecular docking experiments. Eleven target proteins, (AKT1, SLC6A4, ADRB2, MAOA, ACHE, ESR1, CYP3A4, CHRNA7, GABRA2, HTR2A and NOS3), which also play significant roles in regulating serotonergic, cholinergic, dopaminergic and GABAergic systems in the PPI network, were selected to act as receptors in molecular docking trials. The results showed that docking pairs isorhamnetin-AKT1, isorhamnetin-SLC6A4, β-sitosterol-MAOA, β- sitosterol-ACHE, isorhamnetin-CHRNA7 and shinpterocarpin-GABRA2 provided the most stable conformations of ligand-receptor binding between key compounds and core target proteins in the SNS. Conclusion: In the study, we offer a computational result, revealing that SNS may alleviate sleep disorders associated with anxiety through a “multi-compounds, multi-targets, and multi-pathways” mechanism. The network-pharmacology and molecular docking outcomes could theoretically confirm the anti-anxiety and anti-insomnia effects of SNS. Although this research is purely statistical and systematic without empirical validation, it serves as a stepping stone and cornerstone for subsequent experimental investigations.

Introduction: Yi-Gan-San, Parkinson's disease, tremor-dominant, network pharmacology, molecular docking, Uncaria rhynchophylla. Methods: We identified 75 active compounds within YGS. From these, we predicted 110 gene targets, which exhibited a direct association with PD-DT. PPI network results highlighted core target proteins, including TP53, SLC6A3, GAPDH, MAOB, AKT, BAX, IL6, BCL2, PKA, and CASP3. These proteins potentially alleviate PD-DT by targeting inflammation, modulating neuronal cell apoptosis, and regulating the dopamine system. Furthermore, GO and KEGG enrichment analyses emphasized that YGS might influence various mechanisms, such as the apoptotic process, mitochondrial autophagy, Age-Rage signaling, and dopaminergic and serotonergic synapses. The core proteins from the PPI analysis were selected for the docking experiment. Results: The docking results demonstrated that the most stable ligand-receptor conformations were kaempferol with CASP3 (-9.5 kcal/mol), stigmasterol with SLC6A3 (-10.5 kcal/mol), shinpterocarpin with BCL2L1 (-9.6 kcal/mol), hirsutine with MAOB (-9.7 kcal/mol), hederagenin with PRKACA (-9.8 kcal/mol), and yatein with GAPDH (-9.8 kcal/mol). These results provide us with research objectives for future endeavors in extracting single compounds for drug manufacturing or in-depth studies on drug mechanisms. Conclusion: From these computational findings, we suggested that YGS might mitigate PD-DT via “multi-compounds, multi-targets, and multi-pathways.”

H elminthostachys zeylanica (L.) hook (HZ), has recently gained attention as a potential herbal supplement for managing ulcerative colitis (UC) through its bioactive compounds. To comprehensively investigate HZ's therapeutic effects and underlying mechanisms on UC, we utilized network pharmacology and in vitro and in vivo analyses. The therapeutic potential of HZ was evaluated using a DSS‐induced mouse model of ulcerative colitis, alongside in vitro cellular studies. A network pharmacology approach was first used to predict the active compounds and molecular targets of HZ. Subsequently, integrated experimental techniques—including ELISA, Western blotting, histological analysis, immunofluorescence, flow cytometry, and molecular docking—were employed to validate and support the predicted mechanisms. Network pharmacology analysis identified 15 active compounds in HZ, contributing to its multi‐target synergistic activity and anti‐inflammatory effects. HZ was found to modulate multiple inflammatory pathways, particularly the Toll‐like receptor 4 (TLR4) and NF‐κB signaling pathways, regulating vital inflammatory mediators such as tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and interleukin‐1β (IL‐1β), emphasizing its therapeutic potential in UC. ELISA, Western blot, and histological analyses confirmed that HZ significantly reduced colon inflammation. Immunofluorescence and flow cytometry analyses also demonstrated that HZ alleviated inflammation by regulating TLR4/NF‐κB and CD3 signaling pathways without involving apoptosis. Ultimately, molecular docking further identified core compounds, including Ugonin M, O, K, and R, which exhibited strong binding affinity to critical proteins in the TLR4/NF‐κB pathway, such as TAK1, IKKβ, and RELA, underscoring their role in HZ's anti‐inflammatory mechanisms. Collectively, these findings provide a solid basis for further investigation into the mechanistic effects and broader clinical potential of HZ as a therapeutic approach for UC.

Alzheimer’s disease (AD) is a complex neurodegenerative disorder with multifaceted pathogenesis. Given the clinical need for multi-target interventions, this study elucidated the neuroprotective mechanisms of walnut (Juglans regia L.) against AD-related cognitive impairment. Methods: We characterized 25 bioactive constituents (fatty acids and ellagitannins) and constructed a protein–protein interaction (PPI) network. GO/KEGG enrichment, integrated with Ingenuity Pathway Analysis (IPA), deciphered pharmacological pathways, followed by molecular docking to evaluate ligand–target binding thermodynamics. Network analysis revealed that walnut phytochemicals synergistically modulate the MAPK-mTORC1-TFEB-mediated endolysosomal homeostasis pathway. Molecular docking indicated that ellagitannins (strictinin, pedunculagin, tellimagrandin I) exhibit robust affinities for upstream RAS/RAF/MEK kinases, suppressing pro-pathogenic signaling. Concurrently, gallic acid targeted ABCA1 and TFEB, promoting TFEB activation and nuclear translocation to enhance beta-amyloid clearance and lysosomal biogenesis. This study provides evidence that walnut attenuates AD pathology through “multi-component” reinforcement of the endolysosomal defense system, establishing a mechanistic foundation for walnut as a promising functional food.

Population aging is accompanied by a progressive decline in intrinsic capacity, yet objective measures reflecting underlying physiological changes remain limited. Yin-deficiency constitution in traditional Chinese medicine has been associated with intrinsic capacity impairment, but its structural correlates remain unclear. This exploratory study investigated associations among tongue ultrasonographic characteristics, Yin-deficiency constitution, and intrinsic capacity impairment in older adults. In this exploratory cross-sectional study, community-dwelling older adults attending a traditional Chinese medicine outpatient clinic (n = 123; mean age 71.6 ± 4.6 years) completed the Constitution in Chinese Medicine Questionnaire–Elderly Edition. Tongue thickness and echo intensity were measured using standardized ultrasonographic protocols, and intrinsic capacity was assessed using the Integrated Care for Older People (ICOPE) framework. Higher tongue echo intensity was associated with lower tongue thickness and higher Yin-deficiency scores. In multivariable linear regression analyses, tongue thickness remained strongly associated with tongue echo intensity (β = −0.548, P < .001), whereas the association between Yin-deficiency scores and tongue echo intensity became attenuated and was no longer statistically significant after adjustment for tongue thickness (β = −0.135, P = .079). Yin-deficiency constitution was associated with cognitive impairment (odds ratio = 2.79, 95% confidence interval = 1.13–6.89, P = .026) and visual impairment (odds ratio = 3.74, 95% confidence interval = 1.57–8.96, P = .003), whereas tongue echo intensity alone was not independently associated with ICOPE-defined intrinsic capacity impairments. Thickness-adjusted sensitivity analyses showed attenuated but directionally consistent findings. Tongue echo intensity appears to reflect structural variation in tongue musculature rather than an independent constitution-specific characteristic. Yin-deficiency constitution was associated with cognitive and visual impairment, whereas tongue echo intensity was not independently associated with ICOPE-defined intrinsic capacity impairments. These findings are exploratory and require validation in larger multicenter cohorts.