Combinatorial Chemistry & High Throughput Screening - Volume 28, Issue 12, 2025

Shen Qi Gui oral liquid (SQG) may be beneficial for chemotherapy-induced myelosuppression (CIM). However, the underlying mechanism of CIM treated with SQG is still lacking.

A total of 27 blood samples from cancer patients were selected to perform RNA-seq to obtain the Differentially Expressed Genes (DEGs). Then, the active components and target genes of SQG were acquired. Next, the drug targets and DEGs were intersected to obtain the intersection genes, followed by functional enrichment analysis and construction of a drug-compound-gene-disease network. Subsequently, core genes were selected. Then, immune cell infiltration, molecular docking, pharmacokinetic and toxicity prediction, and RT-qPCR were performed.

A total of 1,341 DEGs, 51 active compounds, and 264 target genes were identified. Then, 30 intersection genes were acquired. Next, a drug-compound-gene-disease network was constructed, and 7 core genes were acquired. Immune infiltration analysis exhibited that only T follicular helper cells were significantly increased in the CIM group, which was significantly negatively correlated with MAPK1, MAPK14, MCL1, PTEN, and PTGS2. The luteolin, quercetin, and beta-sitosterol showed better affinity with core genes. Luteolin and quercetin, which satisfied Lipinski's rule of five, were likely absorbed by the gastrointestinal system. Toxicity predictions showed that neither luteolin nor quercetin exhibited carcinogenicity or hepatotoxicity.

PTEN, PTGS2, CCL2, FOS, MCL1, MAPK1, and MAPK14 were identified as the core genes in CIM patients, which were involved in the MAPK and PI3K-Akt signaling pathways. Luteolin and quercetin may be the promising drugs against CIM.

Overexpression of SLC16A3 can contribute to the development of various tumors by regulating metabolism, but a systematic analysis of SLC16A3 in bladder cancer (BC) has been rarely reported.

We used the BC datasets from public databases to investigate SLC16A3 expression in BC. We first analysed the relationship between SLC16A3 expression and clinical characteristics of 412 bladder cancer patients. After that, gene function analyses and immunocorrelation analyses of SLC16A3 were conducted with the R package. For immunotherapy effect and drug sensitivity analysis, we also used the R package. We also analysed the relation between SLC16A3 expression and 20 m6A modification key genes. Finally, we determined the expression localization of SLC16A3 in bladder cancer by single-cell sequencing analysis using 3,115 BC cells. We further detected the expression of SLC16A3/MCT4 on BC samples by reversed transcription-quantitative polymerase chain reaction and immunohistochemistry.

The SLC16A3 was overexpressed in BC cells, including epithelial cells (p<0.001). The high SLC16A3 expression level of patients with BC was significantly related to poor prognosis (p=0.044), and we established a reliable prognosis model for BC patients. Statistically significant associations between SLC16A3 and m6A modification (ALKBH5) gene (p<0.001), key genes in aerobic glycolysis, M2 macrophage infiltration (p=0.0058), and immune checkpoint regulation were observed.

Overexpression of SLC16A3 is an independent prognostic factor in patients with BC. SLC16A3 may influence the immune infiltration of BC by regulating BC metabolism and m6A methylation, which ultimately can lead to the progress of BC. For the detection and therapy of BC, SLC16A3 may be a potent therapeutic target for BC.

Knee osteoarthritis (KOA) is a common degenerative joint disease characterized by cartilage degradation, inflammation, and pain. Traditional Chinese Medicine, including JDJM (a herbal formula derived from the renowned Du Huo Ji Sheng Tang), has been used to alleviate symptoms of KOA, but its underlying mechanisms remain unclear.

This study aims to elucidate the potential therapeutic mechanisms of JDJM in treating KOA through network pharmacology, weighted gene co-expression network analysis (WGCNA), molecular docking, and experimental validation in animal models.

The active compounds of JDJM were identified through TCMSP database searches, and their potential targets were predicted using network pharmacology. WGCNA was employed to identify key modules and hub genes associated with KOA. Molecular docking was performed to assess the binding affinities of key compounds to critical inflammatory targets. Molecular dynamics (MD) simulations were used to evaluate the stability of the protein-ligand complexes. An experimental KOA model in rabbits was used to validate the therapeutic effects of JDJM. Histopathological examinations and inflammatory marker analyses were conducted to confirm the findings.

Network pharmacology and WGCNA analyses identified 21 key targets and pathways potentially involved in the therapeutic effects of JDJM. Molecular docking results showed that Glyasperin C had the highest docking scores with EGF and IL-1β, followed by Stigmasterol with IL-6, Myricanone with INS, and Sesamin with VEGFA. MD simulations confirmed the stability of these protein-ligand complexes, indicating strong and stable interactions. In the rabbit KOA model, JDJM treatment significantly improved knee joint morphology and reduced the levels of inflammatory markers, such as IL-6 and TNF-α. Histopathological analysis revealed reduced cartilage degradation and inflammation in the JDJM-treated group compared to controls.

JDJM exhibits promising anti-inflammatory and cartilage-protective effects, making it a potential therapeutic option for KOA patients. Further experimental and clinical studies are warranted to confirm these findings and translate them into clinical practice.

Hemerocallis citrina Baroni (Huanghuacai), a plant of the genus Hemerocallis in the family Asphodelaceae, is widely planted in China. Based on our survey results, the chemical compounds in the essential oil of the flowers of Hemerocallis citrina Baroni (EOFHCB) and relevant pharmacological activities have never been studied systematically.

To preliminarily decipher the pharmacological activities and mechanisms of EOFHCB in the treatment of anxiety disorders by GC-MS, Network Pharmacology, and Molecular docking.

EOFHCB compositions were identified using GC-MS, and their targets were predicted using Swiss Target Prediction databases. The targets of anxiety disorders were obtained by GeneCards, DisGeNET, and OMIM databases. The STRING database was used to construct the protein-protein interaction networks, and the DAVID database was used to carry out GO enrichment and KEGG pathway enrichment analysis. The EOFHCB-components-targets-pathways-anxiety disorders network was constructed by Cytoscape software (Version 3.10.0). Finally, the result was verified by molecular docking.

28 chemical components were identified by GC-MS, including 3-furanmethanol (28.43%), 2-methyl-1-butanol (27.13%), nerolidol (10.62%), and so on, which correspond to 241 potential targets. Several 2440 biological processes, 187 cellular compositions, and 311 molecular functions were enriched by GO enrichment analysis and 174 pathways by KEGG enrichment analysis. The key targets are PTGS 2, SRC, DRD 2, ESR 1, MAOB, and SLC6A4. The most important pathway is the neuroactive ligand-receptor interaction.

EOFHCB exerts its therapeutic effects on anxiety disorders through multi-components, multi-targets, and multi-pathways, which provided new ideas and methods for the in-depth research of aromatic Chinese medicine in the treatment of anxiety disorders.

Oral Mucositis (OM) is a common and highly symptomatic complication of cancer therapy that affects patient function and quality of life. Jingzhi Niuhuangjiedu Tablet (JNT) is derived from the famous Chinese herbal formulas Huanglian Jiedu and Fangfeng Tongsheng decoctions, which have been widely used to treat heat toxin syndrome diseases, such as acute pharyngitis, periodontitis, oral ulcers, and oral mucositis (OM), but the underlying mechanism remains unclear.

This study validated the efficacy and explored the potential mechanisms of JNT in the treatment of OM by integrating network pharmacological analyses and experimental verification.

Network pharmacology and molecular docking techniques were used to predict the active components, key targets, and potential mechanisms of action of JNT against OM. The rat OM model was established by administering 5-Fluorouracil (5-FU) and acetic acid to the rat oral mucosa. Lipopolysaccharide (LPS)-treated human gingival fibroblasts (HGFs) were used as an inflammatory cell model. The GFP-NFκB HEK293T cell line was transfected to evaluate the anti-NFκB activity of JNT.

A total of 236 Chinese herbal components and 201 corresponding targets were predicted for OM treatment using JNT. Bicuculine, luteolin, wogonin, and naringenin were identified as the important active compounds, while AKT1, ALB, IL6, MAPK3, and VEGFA were considered to be the major targets. Molecular docking revealed that these active compounds exhibited strong binding interactions with their targets. In vivo and in vitro experiments demonstrated that the anti-OM effect of JNT might be closely related to AKT1, NFκB, caspase-1, and NLRP3, as well as biological processes, such as inflammatory response and oxidative stress.

Network pharmacological and experimental evidence indicates that JNT has a potential therapeutic effect on OM by regulating the Akt/NFκB/NLRP3 pathway.