Objective: This study aimed to investigate the comorbid mechanisms linking type 2 diabetes mellitus (T2DM) and vascular dementia (VaD), focusing on the roles of astrocytes and neurons, and to identify potential therapeutic traditional Chinese medicines (TCMs) and compounds.
Methods: T2DM (GSE161355) and VaD (GSE122063) transcriptomic datasets were retrieved from the Gene Expression Omnibus database. Differential expression analysis, functional enrichment, and druggability assessment were conducted to identify potential core targets. Corresponding TCMs and compounds were predicted by using the TCMSP and HERB databases, followed by analyses of their pharmacokinetics, toxicity, and binding affinity.
Results: In astrocytes, eight core genes (e.g., HSP90AA1, HIF1A, PTEN) were identified and primarily enriched in autophagy and inflammatory pathways. Eight TCMs, including Corydalis yanhusuo and Phellodendron chinense, were predicted to be relevant. Indigo exhibited a relatively strong binding affinity to HSP90AA1 (-10.0 kcal/mol). In neurons, eight core genes (e.g., NFKB1, CYCS, PTGS2) were enriched in apoptosis and neuro-inflammation pathways. Potential TCMs, such as Tripterygium wilfordii, were identified. Palmatine showed a relatively strong binding affinity to PTGS2 (-8.1 kcal/mol). Most predicted TCMs were characterized as bitter and cold in property, associated with the liver meridian, and attributed with heat-clearing effects.
Conclusion: Our findings suggest that the comorbidity of T2DM and VaD may involve dysregulated inflammatory and apoptotic pathways in astrocytes and neurons. The predicted TCMs and compounds represent multitarget intervention candidates, consistent with TCM theories of "Yin deficiency with internal heat" and "phlegm-stasis transforming into heat." These findings provide a theoretical basis for future experimental validation and the development of TCM-based therapies.
Background: Chronic pelvic inflammatory disease (CPID) is a persistent upper reproductive tract disorder characterized by microbial dysbiosis, pelvic adhesions, and infertility. Guizhi Fuling capsule (GZFLC), a multiherb traditional formula, has demonstrated therapeutic potential for CPID.
Methods: A CPID rat model was established via mixed-pathogen infection. Evaluations included uterine histopathology, inflammatory cytokine levels (interleukin-6, tumor necrosis factor-α, interleukin-18, interleukin-1β), coagulation parameters (prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen), uterine metabolomics, 16S rRNA sequencing, and metagenomic sequencing to assess microbial composition and functional pathway alterations.
Results: CPID rats exhibited weight loss, uterine structural damage, elevated inflammation, and a hypercoagulable state. Uterine metabolomics showed significant reductions in key TCA cycle intermediates (α-ketoglutarate, isocitrate). 16S rRNA sequencing revealed enrichment of the pathogenic bacterium Clostridia_UCG-014. Metagenomic analysis indicated upregulation of quorum sensing (QS) pathway genes (thoil-activated cytolysin, TrbB, Gmr) and downregulation of CAZymes, specifically glycoside hydrolase 2 and carbohydrate esterase 1. Correlation analysis suggested that GZFLC modulates specific microbial taxa, influencing host metabolites and inflammatory responses.
Conclusion: GZFLC likely alleviates CPID by exerting anti-inflammatory effects, restoring TCA cycle energy metabolism, reshaping gut microbiota structure, inhibiting QS signaling, and improving polysaccharide metabolic functions.