NF-κB x PDCD11

The Yiqi Wenyang Huwei Decoction (YWHD) is an herbal formula frequently utilized to treat asthma. Despite its wide usage, the specific mechanism of action remains unknown. Through an in-depth investigation utilizing network pharmacology, molecular docking techniques, and experimental validation, this study aims to uncover the molecular mechanism and material basis of YWHD in the treatment of asthma.

The compounds and targets of YWHD were gathered from various databases such as TCMSP, PubMed, and CNKI. Additionally, asthma-related targets were obtained by combining the GEO dataset with GeneCards and OMIM databases. The STRING platform was employed to establish protein-protein interactions. GO and KEGG pathway enrichment analyses were conducted using DAVID. Molecular docking was utilized to assess the binding affinity between potential targets and active compounds. The asthma rat model was established through OVA induction, and a lung function meter was used to detect Mch-induced Max Rrs. HE staining was conducted to observe pathological changes, while ELISA was used to detect levels of inflammatory factors IL4, IL6, IL13, and IgE in BLAF. Furthermore, qPCR was used to detect levels of IL-1β, IL-6, JUN, and PTGS2 mRNA, while Western blot assay was employed to measure phosphorylation levels of NF-κB and IKKα.

A comprehensive study revealed that YWHD has 188 active compounds and 250 corresponding targets. After conducting a topological analysis of the PPI network, the study identified 14 high-activity targets, including JUN, PTGS2, IL6, IL1B, CXCL8, MMP9, IL10, ALB, TGFB1, CCL2, IFNG, IL4, MAPK3, and STAT3. Further, GO and KEGG pathway enrichment analysis indicated that YWHD targets inflammation-related genes and regulates IL- 17 and NF-kappa B signaling pathways. Animal studies have shown that YWHD can effectively minimize airway Max Rrs, reduce the levels of inflammatory factors IL4, IL13, IL6, and IgE in BLAF, and improve airway inflammation in rats with asthma. Molecular experiments have also demonstrated that YWHD achieves this by down-regulating the expression levels of IL-1β, IL-6, JUN, and PTGS2 mRNA, inhibiting the phosphorylation modification levels of NF-κB and IKKα, and reducing the levels of inflammatory cytokines IL4, IL13, IL6, and IgE in BALF of rats. Interestingly, molecular docking has revealed that the active compounds in YWHD have a strong binding ability to the screening targets.

This research endeavor systematically explicated the active constituents, prospective targets, and signaling pathways of YWHD for asthmatic intervention. The study provides an innovative notion and dependable resource for comprehending the molecular mechanism and pharmaceutical screening of YWHD in the context of asthma treatment.

The Precancerous Lesion of Gastric Cancer (PLGC) is an early stage in the development of gastric cancer. The clinical application of HPXLD has been found to be effective in treating PLGC, but the mechanism of how HPXLD acts on PLGC is still unclear.

The objectives of this study were to reveal the molecular mechanism of how HPXLD can be used to treat PLGC and investigate this mechanism through bioinformatics and experimental validation.

PLGC-associated target genes were identified through bioinformatics analysis. A rat model of PLGC was induced using N-methyl-N'-nitro-N-nitrosoquanidine (MNNG) in combination with ranitidine, hot saline, ethanol, and intermittent fasting, with interventions by HPXLD. The pathological alterations in gastric mucosa were assessed through Hematoxylin-eosin staining (HE). Immunohistochemistry (IHC) and Western blot analyses were employed to evaluate the changes in expression levels of inflammation-related proteins.

After conducting bioinformatics analysis, it was found that there were 23 HPXLDPLGC crossover genes, which were significantly enriched in the IL-17 signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. The results of HE showed that HPXLD was effective in improving gastric mucosal histopathological changes. Additionally, the IHC results demonstrated that HPXLD was able to downregulate the expression of IL-6, COX-2, MCP- 1, and MMP-9. Furthermore, Western blot analysis revealed that HPXLD was able to downregulate the expressions of IL-6, IL-17RA, ACT1, NF-κB, and TNF-α.

HPXLD has been shown to improve PLGC by reducing the expression of inflammation- related proteins. This suggests that HPXLD may potentially be a treatment option for PLGC.

Alzheimer's disease (AD) is a neurodegenerative disease that leads to dementia, but effective treatments are lacking. This study aims to evaluate the therapeutic effects of Gegen Qinlian Decoction (GGQLD) on AD and investigate the underlying mechanisms.

Using network pharmacology and bioinformatics, we identified 376 active ingredients of GGQLD and 427 drug targets. Among these, 7 potential targets (CASP1, MKI67, NFKB1, TLR4, NLRP3, IL1B, and AKT1) were identified as intersecting targets of both GGQLD and AD. Functional enrichment analysis revealed that GGQLD regulates pyroptosis-related pathways. In vivo, GGQLD was administered to AD rat models to assess its effects on spatial learning, memory, and brain tissue injury.

GGQLD significantly reduced latency time by 40 % and increased platform crossings by 60 % in AD rats, demonstrating improved spatial learning and memory abilities. It also reduced hippocampal tissue damage and abnormal Aβ deposition. Mechanistically, GGQLD downregulated pyroptosis-related targets (TLR4, NF-κB, NLRP3, IL-1β, and Caspase-1), which were significantly upregulated in AD. ROC analysis demonstrated strong diagnostic significance for these genes, with AUC values exceeding 0.70. Functional enrichment and KEGG analysis further indicated that GGQLD exerts its therapeutic effects through multiple pathways, particularly the NOD-like receptor pathway, Necroptosis, and NF-kappa B pathway.

This study demonstrates that GGQLD improves spatial learning, reduces brain tissue damage, and alleviates inflammation in AD through the regulation of pyroptosis-related pathways, providing evidence for its potential as a therapeutic agent for AD.