Molecular Mechanisms of Danggui Shaoyao Powder in the Treatment of Ulcerative Colitis: A Network Pharmacology Approach with Experimental Validation.

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.