Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the intestinal tract. Imbalanced intestinal immune homeostasis, particularly macrophage pyroptosis, plays a central role in the pathogenesis of IBD. Pyroptosis is a pro-inflammatory form of programmed cell death mediated by the gasdermin protein family. It is characterized by cellular swelling, membrane rupture, and the massive release of inflammatory mediators. Under physiological conditions, moderate pyroptosis contributes to the maintenance of intestinal immune homeostasis by eliminating intracellular pathogens and releasing immunomodulatory signals. However, aberrant activation of pyroptosis triggers the excessive release of inflammatory mediators and damage signals that drive the initiation and progression of intestinal inflammation. Recent studies have shown that macrophage pyroptosis is profoundly involved in the pathological evolution of IBD. Upon stimulation by danger signals, macrophages undergo pyroptosis and release a high amount of inflammatory mediators that remodel the local immune network. Macrophage pyroptosis can also directly impair the intestinal mucosal barrier, thereby driving the pathological progression of IBD. This article systematically reviews the molecular mechanisms involved in pyroptosis, summarizes the pathological mechanisms through which macrophage pyroptosis drives IBD progression, and introduces various therapeutic strategies targeting macrophage pyroptosis to alleviate IBD. Finally, this review provides novel perspectives for the mechanistic research and precision treatment of IBD and facilitates the clinical translation of strategies targeting macrophage pyroptosis.

The ferroptosis of intestinal epithelial cells (IECs), an iron-dependent form of cell death driven by lipid peroxidation, has emerged as a critical pathogenic driver of ulcerative colitis (UC). This review summarizes the core hallmarks of IEC ferroptosis in UC—specifically, lipid peroxidation, iron overload, and antioxidant system dysregulation—and describes key regulatory signaling networks, including the Nrf2/HO-1, SLC7A11/GPX4, and AMPK/mTOR pathways. Furthermore, we systematically evaluated emerging therapeutic strategies targeting these mechanisms, categorized into antioxidant activation, iron and lipid metabolism regulation, immune and microbiota modulation, and multitarget interventions. Elucidating this complex ferroptotic regulatory network provides a vital theoretical foundation for the development of novel disease-stage-specific therapeutic paradigms for UC management.

OBJECTIVES:To investigate the molecular mechanism by which Huajie Xiaoliu Formula (HJF) and its active component ursolic acid inhibit colorectal cancer (CRC) cell growth. METHODS:Proteomics was used to analyze the effect of HJF on protein expression profile in CRC xenografts from tumor-bearing nude mice. Serum pharmacochemistry was used to identify the potential active components of HJF. Network pharmacology and molecular docking were employed to predict the interaction between ursolic acid and cuproptosis-related targets. Cellular assays including MTT, wound healing, colony formation, and Western blotting were used to validate the effects of ursolic acid on proliferation, migration, and cuproptosis-related indicators (FDX1, SLC31A1, DLAT, GSH, MDA, pyruvic acid, and Cu²⁺) in HCT-116 and LoVo cells. RESULTS:HJF regulated 628 differentially expressed proteins in CRC, involving pathways related to inflammation, immunity, and metabolism. Ursolic acid was identified as a major blood component of HJF and exhibited a strong binding affinity with the key cuproptosis protein FDX1 (LiDock Score106.813). In HCT-116 and LoVo cells, ursolic acid significantly inhibited cell proliferation and migration, induced intracellular accumulation of Cu²⁺, MDA and pyruvic acid, reduced GSH levels, inhibited cellular DLAT expression, and up-regulated the expressions of FDX1 and SLC31A1. CONCLUSIONS:As one of the key active components in the HJF, ursolic acid inhibits CRC cell growth by inducing cuproptosis via targeting FDX1.

ETHNOPHARMACOLOGICAL RELEVANCE:Pseudostellaria heterophylla (Miq.) Pax (PH) is a traditional folk medicine, which is widely used clinically for digestive system tumors such as esophageal, gastric, colorectal, and liver cancers. The anti-tumor effect and mechanism of PH in colorectal cancer (CRC) deserves further study. AIM OF THE STUDY:The objective of this study is to examine the effects and the underlying mechanisms of aqueous extract of Pseudostellaria heterophylla (Miq.) Pax (AEPH) in the CRC. MATERIALS AND METHODS:The components of AEPH were fully resolved using ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS). The effect of AEPH was evaluated in vivo using the MC38 mouse colon cancer model, and its impact on the tumor microenvironment was analyzed by flow cytometry. Bioinformatics analysis, combined with transcriptome sequencing, was utilized to further investigate the signaling pathways of AEPH in CRC cells. RESULTS:A mass spectrometry analysis identified 371 compounds in AEPH, each with a comprehensive score exceeding 60. In vivo experiments demonstrated that AEPH suppressed the growth of MC38 tumors without exhibiting obvious toxicity. Mechanistic studies revealed that AEPH inhibited the JNK signaling pathway, reduced Chemokine C-C Motif Chemokine Ligand 5 (CCL5) secreted by CRC cells, hindered the recruitment of M2-like tumor-associated macrophages (TAMs), promoted the infiltration of IFN-γ+ CD8+ T cells, and improved the immunosuppressive microenvironment of CRC. CONCLUSION:AEPH contributes to the remodeling of the tumor immune microenvironment primarily through the inhibition of CCL5-mediated recruitment of M2-like TAMs. The findings of this study offer a novel perspective on the potential development of AEPH as a therapeutic agent for CRC.

Myocardial ischemia-reperfusion injury (MIRI) is a life-threatening complication of myocardial infarcts, with inner mitochondrial membrane protein dysfunction involved in MIRI-induced heart injury. The role of outer mitochondrial membrane protein mitochondrial antiviral signaling protein (MAVS) is unknown. Here, we show that MAVS expression increases in infarcted myocardium of male wild-type mice. Global MAVS-knock-out or myocardial-specific MAVS knockdown protects male mice from acute and chronic MIRI. MIRI induces double-stranded RNA in affected myocardium, activating intracellular retinoic acid-inducible gene I (RIG-I) signaling, which leads to MAVS aggregation and subsequent non-canonical downstream signaling. MAVS aggregates recruit tumor necrosis factor-associated factor family 6 (TRAF6) and transforming growth factor-β-activated kinase 1 (TAK1), the activating mitogen-activated protein kinase (MAPK) pathway and apoptosis. MAVS-knock-out reduces c-jun-NH2 terminal kinase (JNK) phosphorylation and apoptosis. JNK inhibition protects against MIRI in wild-type male mice, whereas JNK agonist impairs protection in MAVS-knock-out male mice. MIRI activates RIG-I/MAVS pathway and subsequently triggers the TAK1/TRAF6 complex, leading to the activation of the MAPK/JNK signaling cascade. This sequential activation cascade may serve as a potential therapeutic target for MIRI.

Background: Sperm DNA damage is an important factor associated with male infertility, miscarriage, and adverse health outcomes in offspring. Current detection methods face challenges such as inaccurate assessments, limited evaluation indicators, and poor reproducibility, largely due to design flaws and constraints in measurable parameters. Therefore, there is an urgent need to develop more reliable detection technologies and to establish more precise and comprehensive evaluation standards to address this critical issue. Results: This study developed an innovative biosensor based on terminal deoxynucleotidyl transferase (TdT) and strand displacement (SD) probes, establishing a method for the simultaneous detection of two key biomarkers of sperm DNA damage: DNA breakpoints and apurinic/apyrimidinic (AP) sites. By incorporating standardized reference controls, the assay significantly improved detection accuracy and reproducibility, thereby enhancing clinical assessment efficacy. The method was applied to analyze sperm samples from 40 men with normal semen parameters, 50 asthenozoospermia patients, 48 fertile individuals, and 44 subjects with recurrent pregnancy loss (RPL). Receiver operating characteristic (ROC) curve analysis demonstrated that the combined detection of the mean number of sperm DNA breakpoints (MDB) and AP sites significantly outperformed individual assessments of MDB, DNA fragmentation index (DFI), or AP alone in predicting RPL, exhibiting superior sensitivity and specificity. Significance: This advanced technology enables a more comprehensive and precise quantification of sperm DNA damage, overcoming the limitations of traditional methods that have singular assessment indicators, poor effectiveness, and low reproducibility. In addition to demonstrating better clinical relevance in the diagnosis of recurrent pregnancy loss (RPL) and asthenozoospermia, this approach also provides a powerful tool for research in male infertility and holds significant promise for clinical applications.

The use of hypoxia-preconditioned exosomes (HP-Exos) to modulate intestinal immunity in ulcerative colitis (UC) represents a promising therapeutic strategy. However, the effects of hypoxic preconditioning on exosomes derived from bone marrow mesenchymal stem cells (BMSCs) and the underlying mechanisms in UC treatment remain inadequately understood. This study sought to elucidate the regulatory roles and molecular mechanisms of HP-Exos in the context of UC. HP-Exos were isolated from BMSCs and characterized. We employed hypoxia-inducible factor 1α (HIF-1α)-silenced lentivirus-interfered HP-Exos to assess their effects in both in vivo and in vitro models. A series of experiments were conducted to evaluate the effects of HP-Exos on mitophagy, oxidative stress, and apoptosis in HT-29 cells and colonic tissues and to comprehensively analyze the immunoprotective mechanisms of HP-Exos. The results demonstrated that HP-Exos enhanced mitophagy, inhibited reactive oxygen species (ROS) accumulation and apoptosis in HT-29 cells and colon tissues, and upregulated the expression of Bcl-2 19-kDa interacting protein 3 (BNIP3), a downstream effector of HIF-1α. Conversely, HIF-1α knockdown markedly reversed the increase in mitophagy and the inhibition of apoptosis. Our findings indicate that HP-Exos protect against DSS-induced colitis by mitigating apoptosis and ROS production through HIF-1α-BNIP3-mediated mitophagy.

BACKGROUND:Ulcerative colitis (UC) is a subtype of inflammatory bowel disease (IBD) characterized by chronic inflammation of the colon and rectum. Its pathogenesis is closely associated with dysregulated mucosal immune responses and intestinal barrier dysfunction. Although oleanolic acid (OA), a natural pentacyclic triterpenoid, has shown therapeutic potential for UC, its precise molecular targets and underlying mechanisms remain poorly understood. PURPOSE:This study aimed to investigate the therapeutic effects and molecular mechanisms of OA in dextran sulfate sodium (DSS)-induced colitis in mice, with a specific focus on intestinal Th17 cell modulation and polyamine biosynthesis. METHODS:A DSS-induced colitis model was established in mice and treated with OA. Therapeutic efficacy was assessed through DAI scoring, histopathology, and barrier integrity analysis. Intestinal Th17 cell subsets were characterized by flow cytometry and gene expression profiling. Polyamine biosynthesis was evaluated by Western blot and targeted metabolite detection. Bioinformatics and AAV-mediated overexpression models were used to explore the role of the HSP90β-ODC1 pathway in OA-mediated Th17 remodeling. SPR and Lip-MS were employed to assess the potential of HSP90β as an OA target. In vitro, naïve (CD44⁻CD62L⁺) T cells were isolated from mouse spleens and induced to differentiate into pathogenic/non-pathogenic Th17 subsets to validate OA's effects on Th17 differentiation and polyamine biosynthesis. RESULTS:OA treatment significantly ameliorated DSS-induced colitis, as evidenced by improved body weight, disease activity index, colon length, and histopathology. OA also restored disrupted chemical and epithelial barriers. Mechanistically, OA remodeled intestinal Th17 cell subsets by suppressing their pathogenic traits and enhancing anti-inflammatory phenotypes. This effect was mediated through the inhibition of polyamine synthesis-related pathways in Th17 cells. Notably, bioinformatic and pharmacological analyses identified the HSP90β-ODC1 axis as a key pathway downregulated by OA. Overexpression of HSP90β both in vitro and in vivo partially reversed OA's modulatory effects on Th17 cell subtypes and polyamine biosynthesis. CONCLUSIONS:This study demonstrates that OA alleviates DSS-induced colitis by reshaping intestinal Th17 subsets and restoring mucosal immune balance via suppression of polyamine synthesis, with the HSP90β-ODC1 pathway as a key mediator. These findings support OA as a promising therapeutic agent for mucosal immunomodulation and intestinal barrier protection in UC.

IntroductionColorectal cancer (CRC) represents the third most prevalent form of cancer worldwide, with liver metastasis representing a significant contributor to mortality. The interaction between tumor-associated macrophages (TAMs) and tumor cells plays a pivotal role in the development of colorectal cancer liver metastases (CRLM) and represents a promising avenue for therapeutic intervention. Stachydrine (STA), a compound derived from the Leonurus heterophyllus plant, has been shown to effectively inhibit tumor growth through a range of mechanisms.MethodsThe study employed imaging and histopathology to evaluate the efficacy of STA monotherapy in preventing CRLM. The inhibition of M2 macrophage polarization by STA was confirmed through the use of flow cytometry and immunofluorescence. Subsequently, a series of assays, including quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry, scratch, invasion, and tube formation assays, were conducted to confirm STA’s capacity to impede tumor cell migration, invasion, and angiogenesis in vitro. Western blotting and flow cytometry were employed to elucidate the mechanisms through which STA exerts its effects on tumor metastasis.ResultsIn our research, STA has been shown to attenuate liver metastasis in CRC mouse models by inhibiting the polarization of macrophages to the M2 phenotype. This anti-metastatic effect is dependent on the presence of macrophages. In vitro, STA has been found to impede tumor cell migration, invasion, and angiogenesis by preventing TAMs from polarizing to the M2 phenotype via the JAK2/STAT3 signaling pathway. Moreover, the combination of STA with anti-PD-1 therapy has been observed to restore immune infiltration within the tumor microenvironment and inhibit tumor progression.ConclusionThe findings of this study demonstrate that STA exerts an inhibitory effect on colorectal cancer liver metastasis by targeting macrophages and impeding their M2 polarization via the JAK2/STAT3 pathway. Furthermore, the combination of STA with anti-PD-1 therapy has been observed to enhance the effectiveness of immune checkpoint blockade and reduce tumor spread, indicating the potential of STA to improve the efficacy of immunotherapy for liver metastases.

Background:Compound sophorae decoction (CSD) has been extensively applied in clinic for the treatment of ulcerative colitis (UC). However, the effect and precise therapeutic mechanism have not been fully clarified. In this study, we systematically explored the protective efficacy and the underlying molecular mechanisms of CSD against UC. Methods:The main constituents of CSD were analyzed by HPLC-MS/MS and TLC. H2O2-treated Caco-2 cells were employed to investigate the impact of CSD on ferroptosis and its underlying mechanism. The impacts of CSD on inflammation, oxidative stress, and ferroptosis in vitro were evaluated by ELISA, biochemical detection, or fluorescence probe. The UC model was established in rats by administering 5% DSS in the drinking water. The effects and safety of CSD on DSS-induced colitis were evaluated through daily body weight, DAI, colon length, and HE staining. In addition, cytokines (IL-1β, IL-6, TNF-α, and TGF-β) and ferroptosis-associated parameters (iNOS and PTGS2) were detected by ELISA. Antioxidant and oxidant enzyme activities (SOD, GSH, MDA, and NO) and lipid ROS in serum and colon tissue were measured by biochemical kit. Ferroptosis was determined by analysis of ferroptosis-associated proteins (Keap1, Nrf2, GPX4, and SLC7A11). Results:Then, 10 main active components were identified in CSD. CSD significantly attenuated DSS-induced intestinal injury and inflammation. Moreover, CSD notably decreased oxidative stress and lipid peroxidation. Mechanistically, CSD suppressed ferroptosis in DSS-induced UC and upregulated GPX4 and SLC7A11 expression through the activation of Nrf2 signaling in DSS-induced rats. Conclusions:Collectively, this study demonstrated that CSD ameliorates ferroptosis in DSS-induced UC rats, with its protective effects attributed to the activation of the Keap1/Nrf2/GPX4 signaling pathway.

Colorectal cancer (CRC) represents one of the most prevalent forms of malignant neoplasms affecting the digestive tract. Recent studies have demonstrated that the induction of ferroptosis in tumor cells represents a novel therapeutic strategy. Ononin, an isoflavone glycoside compound derived from traditional Chinese medicinal plants, has garnered attention for its purported therapeutic efficacy. This study integrated network pharmacology and experimental studies to elucidate the underlying mechanism involved in the therapeutic action of ononin against CRC. The results demonstrated that ononin induced lipid peroxidation and a reduction in mitochondrial membrane potential (MMP), indicative of mitochondrial damage in CRC cells, accompanied by a pronounced decline in GPX4 expression. The combination of ononin and anti-PD-L1 therapy demonstrated a notable enhancement in tumor growth inhibition in the MC38 mouse CRC model, accompanied by a marked increase in the proportion of intratumoral IFNγ+CD8+T cells. In summary, ononin triggers ferroptosis in colorectal cancer cells by increasing lipid ROS through the PI3K/AKT/Nrf2 pathway and reducing GPX4 expression. The combination of ononin and anti-PD-L1 therapy shows a synergistic anti-tumor effect, effectively inhibiting tumor growth and enhancing immune response. This study demonstrates that ononin is a promising therapeutic agent for CRC and may potentially serve as an immuno-adjuvant to enhance immunotherapy efficacy.

The efficacy and safety of secukinumab up to week 52 in children and adolescents with moderate-to-severe chronic plaque psoriasis have been demonstrated previously (NCT03668613). Herein, we report the long-term efficacy, safety, and tolerability of secukinumab over a period of up to 208 weeks. In this randomized open-label trial, patients (6 to < 18 years) were randomized 1:1 to receive low-dose (LD; N = 42) or high-dose (HD; N = 42) secukinumab stratified by weight (< 25 kg, 25 to < 50 kg, or ≥ 50 kg) and disease severity (moderate or severe). Patients weighing < 25 kg received 75 mg secukinumab (both LD and HD); 25 to < 50 kg received 75 mg (LD) or 150 mg (HD) secukinumab; and ≥ 50 kg received 150 mg (LD) or 300 mg (HD) secukinumab. The study assessed Psoriasis Area and Severity Index (PASI) 75/90/100 response, Investigator’s Global Assessment modified 2011 (IGA mod 2011) 0/1 response, Children’s Dermatology Life Quality (CDLQI) 0/1 response, and safety. The impact of secukinumab treatment on physical development was also assessed. Overall, 79.8

ETHNOPHARMACOLOGICAL RELEVANCE:Compound sophora decoction (CSD), a widely used Chinese herbal formula, has been shown to effectively alleviate symptoms ulcerative colitis (UC), including of bloody diarrhea, tenesmus, abdominal pain, and fever. Despite its clinical use, the precise pharmacological mechanisms of CSD remain enigmatic. AIM OF THE STUDY:This study aims to investigate the potential efficacy and underlying mechanisms of CSD in the treatment of UC by employing an integrative pharmacology-based approach, molecular docking analysis and experimental validation. MATERIALS AND METHODS:In this study, an integrative pharmacology-based approach was employed to predict the primary pathway through which CSD treats UC. The mechanism of CSD was further validated using a DSS-induced UC mouse model. Disease severity was assessed by monitoring stool property, body weight, colon length, and colon histopathology. Colonic pathological changes were examined using hematoxylin and eosin (HE) staining. The concentration of cytokines was measured via ELISA, while key molecules in the PI3K-AKT pathway and autophagy-related markers were evaluated using Western blotting. Autophagy in intestinal epithelial cells was observed using electron microscopy. RESULTS:The results demonstrated that CSD alleviated DSS-induced UC by inhibiting the activation of PI3K-AKT pathway, reducing the release of inflammatory cytokines, down-regulating oxidative mediators, and enhancing autophagy. Moreover, the protective effects of CSD were diminished by bpV, a PTEN inhibitor, further supporting the involvement of the PI3K-AKT pathway. CONCLUSIONS:The underlying mechanism of CSD's therapeutic effect on UC may involve significant attenuation of DSS-induced intestinal inflammation by promoting autophagy through the inhibition of PI3K-AKT pathway activation.

Background Nourishing Blood Diuretic Formula (NBDF) is derived from the empirical formula of Prof. Fan Heng in the Department of Traditional Chinese Medicine (TCM), Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, which consists of 8 Chinese herbs, namely Abelmoschi corolla, Rhei Radix et Rhizoma, Astragali Radix, Angelicae Sinensis Radix, Poriae Cutis, Dioscoreae Rhizoma, Hirudo, Bombyx Batryticatus. This formula is designed based on the pathogenesis of chronic kidney disease (CKD) in TCM.Objective This study aims to investigate the efficacy and reveal the mechanism of action of NBDF for the treatment of chronic renal failure (CRF) by cell and animal experiments.Methods TGF-beta 1 protein was used to induce human renal tubular epithelial cells (HK-2) to produce fibrosis, and different concentrations of NBDF-containing serum were given to detect the levels of Fibronectin and E-cadherin in HK-2 cells of each group after drug administration. Adenine gavage was used to make a rat model of chronic renal failure, and after the groups were finished administering the drug, the blood and kidneys were collected and used to detect renal function indexes and protein expression.Results NBDF can significantly improve the fibrosis of HK-2 cells, and improve renal function and renal fibrosis and reduce renal injury in model rats, and its mechanism of action may be related to the regulation of TGF-beta/Smad signaling pathway.Conclusion This study investigated the therapeutic effect and mechanism of action of chronic renal failure from cellular level and animal model, and provided experimental basis for the development of new drugs.

INTRODUCTION:Ulcerative colitis (UC) is a refractory disease with complex pathogenesis, and its pathogenesis is not clear. The present study aimed to investigate the potential target and related mechanism of Compound Sophora Decoction (CSD) in treating UC. METHODS:A network pharmacology approach predicted the components and targets of CSD to treat UC, and cell and animal experiments confirmed the findings of the approach and a new target for CSD treatment of UC. RESULTS:A total of 155 potential targets were identified for CSD treatment of UC, with some related to macrophage polarization, such as nitric oxide synthase (NOS2), also known as inducible nitric oxide synthase (iNOS). GO and KEGG enrichment analysis indicated that oxidative stress response and multiple inflammatory signaling pathways such as TNF-α may play a significant role. In vitro experiments revealed that Interferon-stimulated DNA (ISD) interference can cause polarization imbalances in Raw 264.7 and bone marrow-derived macrophages (BMDMs). Flow cytometry demonstrated that polarization of macrophages in the intestine, spleen, and lymph nodes in vivo was also unbalanced after dextran sulfate sodium (DSS) modeling with pathological intestinal injury. Both in vitro and in vivo studies indicated that after inducing inflammation, the levels of macrophage polarization-related markers (iNOS and Arg1) and inflammation-related factors (CCL17, IL10, TNF-α, and CXCL10) changed, accompanied by increased expression of cGAS. However, CSD treatment based on inflammation can inhibit the expression of cGAS protein and mRNA, lower the level of inflammatory factors, promote the expression of anti-inflammatory factors, and regulate macrophage polarization. CONCLUSION:We concluded that CSD alleviated DSS-induced UC by inhibiting cGAS, thus regulating macrophage polarization.

BACKGROUND Circular RNAs (circRNAs) are involved in the pathogenesis of many diseases through competing endogenous RNA (ceRNA) regulatory mechanisms. AIM To investigate a circRNA-related ceRNA regulatory network and a new predictive model by circRNA to understand the diagnostic mechanism of circRNAs in ulcerative colitis (UC). METHODS We obtained gene expression profiles of circRNAs, miRNAs, and mRNAs in UC from the Gene Expression Omnibus dataset. The circRNA-miRNA-mRNA network was constructed based on circRNA-miRNA and miRNA-mRNA interactions. Functional enrichment analysis was performed to identify the biological mechanisms involved in circRNAs. We identified the most relevant differential circRNAs for diagnosing UC and constructed a new predictive nomogram, whose efficacy was tested with the C-index, receiver operating characteristic curve (ROC), and decision curve analysis (DCA). RESULTS A circRNA-miRNA-mRNA regulatory network was obtained, containing 12 circRNAs, three miRNAs, and 38 mRNAs. Two optimal prognostic-related differentially expressed circRNAs, hsa_circ_0085323 and hsa_circ_0036906, were included to construct a predictive nomogram. The model showed good discrimination, with a C-index of 1(> 0.9, high accuracy). ROC and DCA suggested that the nomogram had a beneficial diagnostic ability. CONCLUSION This novel predictive nomogram incorporating hsa_circ_0085323 and hsa_circ_0036906 can be conveniently used to predict the risk of UC. The circRNa-miRNA-mRNA network in UC could be more clinically significant.

Objective: Analyzing the chemical composition and blood-entry components of Nourishing Blood Diuretic Formula (NBDF) by Liquid Chromatography-Mass Spectrometry (LC-MS), and analyzing the mechanism of NBDF in the treatment of chronic renal failure by combining network pharmacology and molecular docking technology. Methods: The prototype components were obtained by LC-MS, and the targets of the prototype components and the targets for the treatment of chronic renal failure (CRF) were predicted by network pharmacology to obtain the common targets of the drug and the disease, which were then subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and molecular docking was carried out between the compounds of the prototype components and the key targets, so as to screen out the active ingredients, the targets and the signaling pathways that were closely related to the efficacy of NBDF. Results: Synthesizing the test information, 125 compounds were identified from the solution of NBDF, and 48 blood-entry components were identified from rat plasma containing the drug, including 6 prototypical components, and 102 potential targets of action, 515 GO entries, and 133 KEGG pathways were obtained from the web-based pharmacological analyses, and molecular docking was performed to obtain the binding of the 6 prototypical component compounds and the 9 key targets, and the formononetin, emodin, epicatechin, chlorogenic acid, sennoside A, and astragaloside III were hypothesized to be the active components of NBDF in the treatment of CRF. Conclusion: This study initially demonstrated that Nourishing Blood and Diuretic Formula exert its therapeutic effects on CRF through multicomponents, multitargets, and multimethods, and elucidated its pharmacological material basis and therapeutic mechanism.