Aug 2026· Combinatorial chemistry & high throughput screening· 0 citations
Medicine
TL;DR
This study provides experimental evidence supporting the protective effects of DSP against UC, with its actions likely mediated, at least in part, through the modulation of Th17 cell differentiation.
Abstract
INTRODUCTION
Danggui Shaoyao Powder (DSP), a classical prescription in Traditional Chinese Medicine (TCM), has garnered growing evidence for its promising therapeutic effects on ulcerative colitis (UC). Nevertheless, the specific molecular mechanisms responsible for its anti-UC activity remain poorly understood. Herein, we integrated network pharmacology with experimental validation to systematically explore and clarify the underlying mechanisms of DSP in the treatment of UC.
Methods
Network pharmacology was utilized to identify the active components and therapeutic targets of DSP in the treatment of UC. Subsequently, a protein-protein interaction (PPI) network of the identified targets was constructed using the STRING database, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking was performed to evaluate the binding affinity between the primary bioactive components of DSP and Th17-associated proteins. Finally, the protective efficacy of DSP in maintaining immune homeostasis and alleviating inflammation was validated in vivo using a dextran sulfate sodium (DSS)- induced UC mouse model.
Results
A total of 51 active components of DSP and 103 corresponding targets were retrieved from the TCMSP database. Additionally, 4,419 potential targets associated with UC were identified from the OMIM, DisGeNET, and GeneCards databases. Sixty-three overlapping potential targets were identified as therapeutic targets of DSP against UC, which were subsequently refined to construct an optimized protein-protein interaction network containing 100 central nodes. Key hubs included IL-6, AKT1, ESR1, CASP3, PTGS2, BCL2, PPARG, HSP90AA1, TGF-β1, and JUN, and these targets were highly enriched in pathways associated with inflammatory regulation and immune signaling, with Th17 cell differentiation serving as a key biological process. Molecular docking demonstrated stable binding affinities between the DSP components Paeoniflorin and Stigmasterol and the core targets TGF-β1 and IL-6 (binding energy < -5 kcal/mol). Furthermore, in vivo experiments demonstrated that DSP ameliorated symptoms and histological changes in DSS-induced colitis by inhibiting Th17 cell differentiation.
Discussion
This study provides experimental evidence supporting the protective effects of DSP against UC, with its actions likely mediated, at least in part, through the modulation of Th17 cell differentiation. These results deepen our insight into the mechanistic underpinnings of DSP activity and can serve as a theoretical basis for the further advancement of DSP-based therapeutic strategies for UC.
Conclusion
DSP has shown potential as a therapeutic agent for UC by acting on multiple core targets and relevant signaling pathways, with the modulation of Th17 cell differentiation serving as a key mediating mechanism.
Introduction Huangqin decoction (HQD), a traditional Chinese medicine prescription, is used to treat gastrointestinal diseases, including ulcerative colitis (UC). However, systematic research on the components of HQD remains insufficient. Therefore, we aimed to perform chemical profiling, network pharmacology, and bioinformatics analyses of HQD to identify candidate constituents potentially associated with UC and to establish a quantitative method for their determination in HQD. Methods Qualitative chemical profiling was performed to identify 51 compounds in HQD, and their potential targets were predicted. UC-related target genes were identified by combining results from public and Gene Expression Omnibus (GEO) databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the biological processes and signaling pathways associated with UC. Moreover, protein–protein interaction (PPI) analysis was performed. Based on these results, 15 putative active constituents of HQD were selected and quantified. Molecular docking analysis was then performed to evaluate the binding interactions between these compounds and key target proteins. Results A total of 947 HQD component-related, 1,868 UC-related, and 2,930 GEO database-related target genes were intersected to obtain 109 common target genes for HQD and UC. GO and KEGG enrichment analyses indicated that these targets were mainly associated with inflammatory and immune-related biological processes and signaling pathways. Among the identified targets, NOS2, AHR, MMP3, MMP9, and PRKCQ were highlighted as potential key targets. The analysis of three batches of HQD samples revealed that baicalin had the highest content. Molecular docking results indicated favorable predicted interactions between the putative active compounds and core target proteins, with several compound–target pairs exhibiting docking scores below −11.0 kcal/mol. Discussion This study not only provides a comprehensive chemical profile of HQD but also presents a new approach for evaluating and managing quality based on putative active constituents. These findings may serve as a scientific basis for further pharmacological and clinical studies.
Seol Jang, Y. Kim, Youn-Hwan Hwang· Frontiers in Chemistry· 0 citations
ETHNOPHARMACOLOGICAL RELEVANCE
Bupi Yichang Pill (BYP) is a traditional Chinese medicine (TCM) formula with an established clinical history in managing chronic intestinal disorders and has shown promising protective effects against ulcerative colitis (UC). However, its pharmacodynamic basis and underlying molecular mechanisms remain poorly characterized.
AIM OF THE STUDY
This study systematically investigated the pharmacological basis and mechanistic underpinnings of BYP in UC through an integrated strategy combining network pharmacology, multi-omics profiling, and experimental validation.
MATERIALS AND METHODS
A dextran sulfate sodium (DSS)-induced murine UC model was used to evaluate BYP's protective effects, with disease severity assessed by body weight, disease activity index (DAI), colon length, and histopathology, and inflammatory responses quantified by ELISA and RT-qPCR. Chemical constituents were characterized by UPLC-HRMS, and bioactive compounds, targets, and pathways were identified through network pharmacology and molecular docking. Gut microbiota composition, metabolic profiles, and transcriptomic changes were interrogated by 16S rRNA sequencing, untargeted metabolomics, and RNA-seq, respectively. The PI3K/Akt/IKK/NF-κB axis was validated by Western blotting and immunofluorescence in colonic tissues and LPS-stimulated RAW264.7 macrophages.
RESULTS
BYP significantly attenuated DSS-induced colitis, as evidenced by reduced body weight loss, lower DAI scores, preserved colon length, and alleviated mucosal injury. BYP markedly decreased TNF-α, IL-1β, and IL-6 levels while upregulating IL-10. UHPLC-HRMS identified 115 constituents, of which eight-including kaempferol, liquiritin, quercetin, berberine, paeoniflorin, cryptopine, perlolyrine, and glabrone-were prioritized as overlapping bioactive compounds. Network pharmacology implicated key targets including IL6, TNF, AKT1, and PTGS2, and molecular docking confirmed favorable binding affinities. KEGG enrichment highlighted the PI3K/Akt and NF-κB pathways as principal regulatory axes. Multi-omics analysis revealed that BYP restored gut microbiota dysbiosis, ameliorated bile acid and amino acid metabolism, and modulated the expression of inflammation- and barrier-related genes. Western blotting confirmed suppression of PI3K, Akt, IKK, and NF-κB p65 phosphorylation, corroborated by immunofluorescence in both colonic tissue and macrophages.
CONCLUSION
BYP confers protection against DSS-induced ulcerative colitis through a multi-component, multi-target, and multi-level regulatory mechanism. Kaempferol and liquiritin emerge as principal bioactive contributors, acting through UC-associated molecular targets and inflammatory signaling cascades. Integrated multi-omics analyses and experimental validation collectively demonstrate that BYP ameliorates gut microbial and metabolic dysregulation while suppressing PI3K/Akt/IKK/NF-κB pathway activation, providing both a mechanistic basis and pharmacological rationale for its traditional clinical use in UC management.
Yunlu Zou, Zi-Zhao Yang, Jiatong Liu et al.· Journal of Ethnopharmacology· 0 citations
Ulcerative colitis (UC) is a worldwide health issue with limited therapies. Traditional Chinese Medicine (TCM) shows potential, but lacks systematic efficacy evaluation and detailed mechanistic explanations. This study aims to evaluate the efficacy of TCM for active UC and explore its mechanisms. A meta-analysis of RCTs was conducted to assess TCM efficacy in active UC, and treatment efficacy was ranked. Core Chinese herbs were identified via association rule analysis. Network pharmacology and molecular docking predicted active components, targets, and pathways. Efficacy of the key component was validated in active UC mice. 17 studies (1,598 patients) showed TCM significantly improved active UC (SMD -1.73, 95%CI -2.21 to -1.25). Eight core Chinese herbs were identified. Network pharmacology revealed 76 overlapping targets. Isorhamnetin (Iso) showed strong binding to PTGS2 (binding energy: -9.34 kcal/mol) and Nrf2 (binding energy: -9.16 kcal/mol). In vivo, Iso dose-dependently alleviated disease symptoms, pathological damage, and spleen index in UC mice. TCM could ameliorate active UC. The key active component Iso shows therapeutic effects, with mechanisms potentially involving the Nrf2-PTGS2 axis and immune-inflammatory pathways. The findings offer some insight into the scientific basis of TCM in treating UC and predict that Iso may be a candidate for further mechanistic and clinical investigation.
Zhen-Jia Fan, Luqing Zhao, Ning Ding et al.· Naunyn-Schmiedeberg's Archiv...· 0 citations
INTRODUCTION
Antipsychotic-induced hyperprolactinemia (HPRL) is a prevalent and troubling side effect that impairs treatment adherence. Xuefu Zhuyu Pills (XFZY), a traditional Chinese medicine formula, have shown efficacy in clinical practice; however, their active components and mechanisms of action remain unknown.
METHODS
We identified the components of XFZY in human plasma by UPLC-Q-TOF-MS/MS and performed network pharmacology analysis to screen key targets and core active components through topological analysis. Intersecting targets were subjected to GO and KEGG enrichment analyses on Metascape, followed by molecular docking and molecular dynamics simulations to assess binding stability between core active components and key targets.
RESULTS
A total of 67 absorbed components were found in human plasma. Based on the network pharmacology results, we identified seven core targets (AKT1, ESR1, IL6, TNF, ERBB2, CTNNB1, and MAOA) and three potential active ingredients (Makisterone B, 3-O-beta-Dglucopyranosylplatycodigenin, and 4',5,6,7-Tetramethoxyflavone). GO and KEGG suggested that hormone level regulation, the neuroactive ligand-receptor interaction, the apelin signaling pathway, and the cGMP-PKG signaling pathway may play key roles in treating HPRL caused by antipsychotic drugs.
DISCUSSION
Molecular docking results showed that the core active ingredient binds well with the key targets, and molecular dynamics simulations further verified their stability.
CONCLUSION
This study preliminarily revealed the components in human plasma of XFZY in HPRL treatment and their potential pharmacological mechanism. These findings provide a scientific basis for clinical studies.
Mingyue Liu, Zihuan Zhang, Guanli Su et al.· Combinatorial chemistry & hi...· 0 citations
Gout is a disease characterized by hyperuricemia and the deposition of urate crystals in joints and soft tissues, leading to recurrent acute arthritis. Its increasing prevalence imposes substantial clinical and socioeconomic burdens. Sishen Decoction (SSD) has been used in the treatment of gout, but its potential molecular mechanisms remain unclear. This study applied an integrated network pharmacology and molecular docking approach to identify potential targets and signaling pathways associated with SSD in gout. Active compounds and corresponding targets of SSD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), while gout-related targets were collected from the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Overlapping targets were identified and used to construct a drug-component-target-disease network. A protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, followed by molecular docking using the docking server analysis module. A total of 37 bioactive compounds were associated with 116 overlapping gout-related targets. The top hub targets included TP53, IL6, IL1B, TNF, AKT1, EGFR, CASP3, JUN, BCL2, and MMP9. GO analysis suggested that these targets are involved in gene expression regulation and signal transduction. KEGG enrichment analysis indicated significant associations with the mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K-Akt), interleukin-17 (IL-17), and tumor necrosis factor (TNF) signaling pathways. Molecular docking predicted favorable interactions between key compounds and hub targets, with all binding energies of ≤-5 kcal/mol. These computational findings provide potential mechanistic hypotheses for the action of SSD in gout and may support future experimental validation.
Tingting Zhou, Xiandong Liang· Journal of Visualized Experi...· 0 citations
Isatis indigotica (Banlangen) is a classic Traditional Chinese Medicine herbal remedy with well-documented antiviral and anti-inflammatory properties. However, the molecular mechanisms underlying its therapeutic effects against hepatitis B virus (HBV)-associated hepatic inflammation remain incompletely understood. This study aimed to systematically elucidate the multi-target regulatory mechanisms of Isatis indigotica against HBV-associated hepatic inflammation using network pharmacology and molecular simulation approaches. Bioactive compounds were screened from the TCMSP database (OB ≥ 30%, oral bioavailability; DL ≥ 0.18, drug-likeness). Candidate targets were identified by integrating SwissTargetPrediction with GeneCards/OMIM disease targets. Protein-protein interaction (PPI) network topology analysis identified hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using Metascape. Molecular docking and 100 ns all-atom molecular dynamics (MD) simulation were conducted to validate compound-target binding. Seventeen bioactive compounds were identified, yielding 1,023 compound targets. Intersecting with 1,676 HBV disease targets produced 142 candidate genes. PPI network analysis identified AKT1, IL6, TP53, and TNF as hub genes, significantly enriched in NF-κB, JAK-STAT, and TNF signaling pathways (P < 0.01). Molecular docking confirmed favorable binding affinities, with IQ (6-(3-oxoindolin-2-ylidene)indolo[2,1-b]quinazolin-12-one) showing optimal binding to AKT1 (ΔG = −9.35 kcal/mol). MD simulation verified stable binding over 100 ns. This network pharmacology study suggests that Isatis indigotica acts on HBV-associated hepatic inflammation through multi-target synergistic regulation of NF-κB and JAK-STAT signaling pathways, providing mechanistic insights and potential therapeutic targets for HBV management.
Xueru Li, Yang Wang, Huijun Cheng et al.· PLoS ONE· 0 citations
