Search Results (1,131)

Background:Scutellaria baicalensis (Scu) extract has been traditionally used in the treatment of stroke-related syndromes, yet its underlying molecular mechanisms, particularly those involving ferroptosis, remain to be fully elucidated. Purpose: This study aims to validate the hypothesis that Scu extract improves cerebral ischemia-reperfusion injury (CIRI) by inhibiting ferroptosis through the PI3K/AKT signaling pathway. Methods: This study employed middle cerebral artery occlusion (MCAO) in male Sprague-Dawley (SD) rats and oxygen–glucose deprivation/reoxygenation (OGD/R) models to evaluate the protective effects of Scu extract against CIRI. Multiple approaches were integrated to elucidate the underlying mechanisms. Furthermore, a range of experimental techniques, including neurological function assessment, TTC staining, histopathological analysis, biochemical assays, qPCR, transmission electron microscopy (TEM), reactive oxygen species (ROS) detection, Western blotting, and immunofluorescence, were used to comprehensively validate its neuroprotective effects. Results: Scu extract significantly improved neurological outcomes and attenuated brain injury in MCAO rats. Proteomic analysis revealed significant enrichment of ferroptosis-related pathways, which was supported by reduced mitochondrial damage, decreased iron accumulation, and restoration of the SLC7A11/GPX4 axis. Subsequently, UPLC/Q-TOF-MS analysis revealed that four major bioactive components were absorbed in MCAO rats. KEGG pathway analysis based on network pharmacology further indicated that the PI3K/AKT signaling pathway is a key regulatory target. Notably, pharmacological inhibition of PI3K with LY294002 markedly abolished the anti-ferroptotic effects of Scu extract, which was further confirmed in vitro. Conclusions: This study demonstrates that Scu extract confers neuroprotection against CIRI in MCAO rats potentially through inhibiting ferroptosis via activation of the PI3K/AKT pathway. Full article

This study focuses on the synthesis of glucovanillin mediated by UGT109A1 and its mechanism against Type 2 Diabetes Mellitus (T2DM). Recombinant UGT109A1 successfully synthesized glucovanillin from vanillin using UDP-Glc as the sugar donor. Through network pharmacology, 140 potential targets were identified. Seven key targets were further screened using LASSO and SVM-RFE algorithms. Among these, SLC5A1 and ADK showed strong diagnostic potential, with AUC values ranging from 0.85 to 0.89. Immune infiltration analysis linked these core targets to M2 macrophages. Single-cell transcriptomics revealed that ADK is widely expressed but enriched in B cells, while TLR9 is confined to plasmacytoid dendritic cells (pDCs). Cell-to-cell communication analysis identified a pDC-to-B cell signaling axis. In vitro assays demonstrated that glucovanillin exhibits concentration-dependent inhibitory activity against α-glucosidase with moderate potency, with an IC₅₀ of 413.84 ± 12.80 μM. Molecular docking, 200 ns molecular dynamics simulations (MD), and MM/PBSA calculations showed that glucovanillin binds more strongly to α-glucosidase (−7.4 kcal/mol) than vanillin (−5.4 kcal/mol). Therefore, the glycosylation mediated by UGT109A1 enhanced the bioactivity and targeting specificity of vanillin. In summary, glucovanillin exerts anti-T2DM effects through a dual mechanism involving α-glucosidase inhibition and regulation of key targets, making it a promising lead compound for T2DM treatment. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by β-amyloid (Aβ) accumulation and a breakdown of mitochondrial homeostasis. Vitamin K2 (VK2) has emerged as a potential neuroprotective agent, yet the specific molecular cascades linking its intervention to the restoration of mitochondrial integrity remain poorly understood. This study utilizes an AD Drosophila model to investigate the efficacy of VK2 and elucidates its multidimensional regulatory mechanisms. Behavioral analysis showed that VK2 significantly rescued locomotor impairments, improving both vertical climbing and horizontal walking performance. Crucially, VK2 intervention achieved a systemic rescue of mitochondrial health: transmission electron microscopy (TEM) confirmed the preservation of mitochondrial ultrastructure and cristae density, while biochemical assays demonstrated a robust recovery of bioenergetic markers, including ATP levels and the NAD⁺/NADH ratio. Furthermore, VK2 treatment stabilized the mitochondrial membrane potential (MMP) and effectively attenuated the accumulation of reactive oxygen species (ROS). To identify the molecular drivers of this recovery, an unbiased integration of human clinical transcriptomic data and network pharmacology prioritized the EGFR-Ras-ERK signaling axis as a central hub. In vivo validation confirmed that VK2 suppresses the pathological overactivation of this cascade. VK2 reduced EGFR phosphorylation in parallel with the effects observed for the EGFR inhibitor Gefitinib. Collectively, our findings show that VK2 ameliorates locomotor deficits and mitochondrial dysfunction in Aβ42-expressing flies and that these effects are associated with suppression of the EGFR-Ras-ERK signaling axis. Further studies are required to establish direct target engagement and pathway causality. Full article

Palmatine chloride (berbericinine, C₂₁H₂₂ClNO₄) is a protoberberine alkaloid found in several plants, including Rhizoma Coptidis, Cortex Phellodendri, Rhizoma Corydalis, Guduchi (Tinospora cordifolia), and Tinospora sagittata roots. Palmatine chloride (PA) is known as an inhibitor of dopamine generation. However, its effect on endoplasmic reticulum (ER) stress-related macrophage activation caused by endotoxin (lipopolysaccharide) is not yet well known. In this study, the effects of PA on pyroptotic responses of mouse macrophages (RAW 264.7) activated by endotoxin were investigated using Griess reagent assay for nitric oxide (NO) production, fluo-4 assay for cytosolic calcium release, dihydrorhodamine 123 assay for hydrogen peroxide production, multiple cytokine assay for cytokine production, real-time PCR for inflammatory gene transcriptions, and flow cytometry assay for p38 MAPK activation. Preliminary experiments using THP-1 human monocytic cells demonstrated that PA was not cytotoxic and significantly reduced basal NO production. Results revealed that PA significantly reduced excessive production levels of NO, hydrogen peroxide, pro-inflammatory cytokines (such as interleukin (IL)-6, CCL3 (MIP-1α), and CSF2 (GM-CSF)), and cytosolic calcium release in endotoxin-stimulated RAW 264.7, but significantly increased the production of anti-inflammatory cytokine IL-10. PA inhibited endotoxin-induced transcripts of Chop, Stat1, Fas, and c-Fos in activated RAW 264.7. It also decreased p38 MAPK phosphorylation and level of Fas in RAW 264.7 stimulated by endotoxin. To further interpret these findings, a network pharmacology-informed analysis based on large-scale literature mining was performed, supporting the multi-target regulatory role of PA in ER stress-related pathways. Briefly, PA exerts anti-inflammatory effects on endotoxin-stimulated RAW 264.7 via the calcium-CHOP pathway, consequently reducing endotoxin-induced production of pro-inflammatory mediators (NO, cytokines, etc.) and relieving ER stress-related pyroptotic cascade. Full article

Inflammatory bowel disease (IBD) poses a significant global health burden with rising incidence, particularly in Asia. This study employed an integrative network pharmacology approach combined with molecular docking to elucidate the therapeutic mechanism of ganoderic acid A (GAA) against IBD. Potential GAA targets were retrieved from pharmacogenomic databases, while IBD-related genes were curated from OMIM and GeneCards databases. Weighted gene co-expression network analysis of IBD transcriptomic datasets (GSE38713, GSE126124) identified disease-associated modules, with the yellow module exhibiting the strongest positive correlation. Functional enrichment analyses demonstrated significant involvement of overlapping targets in lipid metabolism, the inflammatory response, and the mitogen-activated protein kinase (MAPK) signaling cascade pathway. We identified 14 IBD-GAA-ferroptosis-related genes and 54 key module genes. Intersection analysis revealed 5 overlapping targets, including tumor necrosis factor-α(TNF-α), peroxisome proliferators-activated receptor γ (PPARγ), MAPK14, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic α (PIK3CA), and Caspase 3 (CASP3). Molecular docking confirmed high-affinity binding of GAA to these targets, with binding energies ranging from −7.3 to −10 kcal/mol. Crucially, experimental evaluation demonstrated the pivotal role of GAA in alleviating disease pathology. GAA treatment suppressed the significantly elevated levels of TNF-α and p-MAPK14 in the organoids using a cytokine/LPS-induced IBD model. These findings collectively suggest a potential involvement of GAA in pathways associated with ferroptosis regulation, although direct experimental evidence for ferroptosis markers remains to be established. The observed multi-target effects on immune regulation and cellular proliferation/differentiation provide a foundation for further mechanistic investigation. Full article

Hepatocellular carcinoma (HCC) is a lethal malignancy requiring novel therapeutic interventions. While Polyporus umbellatus exhibits anti-tumor properties, its specific bioactive pharmacophores and molecular mechanisms remain elusive. This study integrated network pharmacology, computational simulation, and experimental validation to decipher the anti-HCC efficacy of Polyporus umbellatus. Screening identified 11 bioactive sterols, with intersection analysis revealing 63 core targets. Clinical data stratified Checkpoint Kinase 1 (CHEK1) as a critical high-risk oncogene associated with poor prognosis. Molecular dynamics simulations (100 ns) demonstrated that polyporusterone E, a key constituent, forms a thermodynamically stable complex with CHEK1 via high-affinity hydrogen bonding. In vitro assays in HepG2 and HuH-7 cells confirmed that CHEK1 overexpression drives proliferation and metastasis, while its silencing reverses these phenotypes. Crucially, treatment with Polyporus umbellatus extract and purified polyporusterone E significantly compromised HCC cell viability and downregulated CHEK1 expression at transcriptional and translational levels. These findings suggest that polyporusterone E may downregulate CHEK1 expression and modulate CHEK1-associated signaling in HCC cells, providing preliminary evidence for the molecular basis of Polyporus umbellatus and highlighting its potential as a complementary therapeutic strategy for HCC management. Full article

Diabetic nephropathy (DN) is a severe diabetic complication with substantial clinical burden. The complex pathogenesis of DN has hindered the development of targeted therapies, creating an urgent need to develop novel strategies that directly address its underlying inflammatory and fibrotic mechanisms. Coreopsis tinctoria (CE) is an edible plant rich in polyphenols, but its mechanism against DN remains understood. An integrated framework combining network pharmacology and machine learning was developed to prioritize active polyphenols and their targets. A multi-layer perceptron classifier, trained on 3.16 million compound–target pairs from Binding DB, predicted interactions between 36 CE polyphenols and 12,030 DN-associated genes. The top 100 targets were subjected to KEGG enrichment analysis, and the identified pathways were validated in a high-fat diet/STZ-induced DN rat model. The MLP model achieved superior performance (AUC-ROC = 0.9219, AP = 0.9592). Five lead polyphenols (flavonoids/chalcones) showed high predicted activity. KEGG analysis revealed enrichment in PI3K-Akt, calcium signaling, metabolic pathways, and cellular senescence. In vivo, CE treatment (150–600 mg/kg/day) dose-dependently improved glucose/lipid metabolism and renal function, and ameliorated histopathological damage, including glomerular hypertrophy, fibrosis, and mesangial expansion. Mechanistically, CE suppressed NFκB/TGFβ/Smad signaling, restored PPARγ and Nrf2/HO-1/FoxO1 antioxidant defenses, and inhibited apoptosis via Bcl-2/Bax regulation. CE exerts multi-target renoprotective effects through coordinated modulation of metabolic, inflammatory, fibrotic, and antioxidant pathways, supporting its potential as a functional food ingredient for DN management. Full article

Background/Objectives: Telomeres are critical biomarkers of biological aging, with shortened leukocyte telomere length strongly linked to all-cause mortality and age-related disease risk. Although exercise modulates telomere dynamics, the field’s evolution from descriptive measurements to mechanistic inquiries involving redox biology and epigenetics remains incompletely mapped. This study systematically characterized the global research landscape of telomere–exercise science over 25 years to establish a strategic evidence base for precision exercise prescription. Methods: A bibliometric analysis was conducted on 858 publications from the Web of Science Core Collection (2000–2025). CiteSpace and VOSviewer were used for keyword co-occurrence analysis, strategic thematic mapping, and citation burst detection to visualize global research trends and identify emerging frontiers. Results: Annual publication volume grew from 2 (2000) to 71 (2025), with a compound annual growth rate of 15.4%. China emerged as one of the leading global contributors. Thematic analysis revealed a paradigm shift from descriptive leukocyte telomere length studies toward mechanistic investigations of oxidative stress, mitochondrial homeostasis, and epigenetic clocks. Keyword network analysis confirmed oxidative stress and inflammation as central hubs, mediating telomere protection via redox regulation and non-canonical telomerase functions. Conclusions: Exercise preserves telomere integrity primarily through redox–mitochondrial homeostasis, hormesis-driven antioxidant upregulation, and non-canonical telomerase activation. For aging populations and individuals at metabolic risk, aerobic training and high-intensity interval training (HIIT) are recommended as first-line non-pharmacological interventions for healthspan extension. Leukocyte telomere length and telomerase activity should be integrated as biomarkers in preventive medicine practice. Future large-scale randomized controlled trials incorporating multi-omics approaches and sex-stratified analyses are warranted to establish individualized dose–response guidelines for precision exercise prescription. Full article

Developing functional foods that address both oxidative stress and physiological challenges like dysphagia is a critical frontier in personalized nutrition. This study investigates the multi-component synergy of Fu Ling Yin Zi (FLYZ), a traditional dietary therapy, and translates its functional properties into a 3D-printed dysphagia-friendly food. Using response surface methodology, the optimal FLYZ formulation was established at a 5:1:5 ratio of Poria cocos (Schw.) Wolf., Amygdalus communis Vas, and Citrus reticulata. Network pharmacology and molecular docking suggested that FLYZ’s active compounds (e.g., nobiletin, stigmasterol, tangeretin, l-SPD, glabridin, estrone) may mitigate oxidative stress via multiple targets (PTGS2, AKT1, TNF, ESR1, MMP9, and MAOA), with pathway analysis pointing to a potential role of the AKT1/GSK3β/HIF-1α axis. Subsequent in vitro cellular assays demonstrated that FLYZ enhanced antioxidant enzyme activities, reduced intracellular ROS, and modulated the expression of associated genes, supporting a potential link to this pathway. To actualize these functional benefits for patients with swallowing difficulties, a novel 3D-printing ink incorporating FLYZ and walnut oil within a hydrogel matrix (3% xanthan gum, 3% pectin, 1.5% carrageenan) was developed. The printed constructs exhibited excellent shape fidelity and, based on standardized IDDSI fork and spoon tests, were categorized as level 4 (pureed/extremely thick). Furthermore, a simulated in vitro digestion model showed that the colloidal network significantly protected FLYZ’s polyphenols and flavonoids, markedly improving their bioaccessibility and post-digestion antioxidant capacity. Collectively, this work establishes an integrated approach that combines predictive molecular profiling with advanced 3D food printing, thereby supporting the development of future foods tailored for personalized nutrition. Full article

Skin aging is associated with oxidative stress, extracellular matrix degradation, and dysregulation of melanogenesis, leading to wrinkles, loss of elasticity, and hyperpigmentation. Natural plant-derived compounds have attracted increasing interest as multifunctional cosmetic ingredients due to their antioxidant and anti-aging properties. Mai-Kae-Den-Klong (MKDK), a traditional Thai longevity herbal formula composed of Albizia procera (Roxb.) Benth., Cyperus rotundus L., Diospyros rhodocalyx Kurz, Piper nigrum L., Streblus asper Lour., and Tinospora crispa (L.) Hook.f. & Thomson, has historically been used to promote vitality and healthy aging; however, its potential application as a cosmetic anti-aging ingredient remains scientifically unexplored. Therefore, this study investigated the anti-aging potential of MKDK extract using integrated enzyme-based bioassays and in silico approaches. Phytochemical profiling of the ethanolic extract was performed using LC-MS analysis, revealing diverse bioactive constituents, including flavonoids, phenolic glycosides, alkaloids, and terpenoids, with (−)-epicatechin, procyanidin B1, and piperine identified as major metabolites. Antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays, while inhibitory activities against tyrosinase, collagenase, elastase, and hyaluronidase were assessed to determine skin anti-aging potential. The extract exhibited strong antioxidant activity, with IC₅₀ values of 17.23 ± 2.11 µg/mL for DPPH and 11.87 ± 1.77 µg/mL for ABTS assays. In addition, the extract demonstrated inhibitory effects against tyrosinase (IC₅₀ = 41.25 ± 1.56 µg/mL), elastase (IC₅₀ = 49.51 ± 3.69 µg/mL), collagenase (IC₅₀ = 61.54 ± 2.88 µg/mL), and hyaluronidase (IC₅₀ = 63.74 ± 6.32 µg/mL), suggesting multifunctional anti-aging properties associated with skin brightening and extracellular matrix preservation. Network pharmacology analysis predicted multiple aging-related signaling pathways, particularly the FoxO signaling pathway, which is associated with oxidative stress regulation and longevity. Molecular docking analysis further demonstrated favorable binding affinities of procyanidin B1, epicatechin, and piperine toward skin-aging-related enzymes, supporting their potential contribution to the observed bioactivities. Overall, these findings suggest that MKDK possesses promising cosmeceutical potential as a natural multifunctional anti-aging ingredient and provides scientific support for the application of traditional Thai herbal formulations in cosmetic and skin health products. Full article

The fruit of Crataegi fructus (CF) is a traditional “medicine food” herb widely used for its lipid-lowering properties, but its active ingredients and mechanisms against metabolic dysfunction-associated fatty liver disease (MAFLD) remain poorly understood. This study employed an integrated multi-omics approach, combining serum metabolomics, liver transcriptomics, weighted gene co-expression network analysis (WGCNA), network pharmacology, and molecular docking, to systematically investigate the effects of CF extract (CFE) in a high-fat diet (HFD)-induced mouse model of MAFLD. Our analysis revealed that CFE treatment significantly reduced body weight gain (p < 0.01), improved glucose tolerance and insulin sensitivity (p < 0.01), and alleviated hepatic steatosis, as evidenced by reduced lipid accumulation and decreased NAS scores (p < 0.001). Metabolomics analysis showed that CFE reversed HFD-induced disturbances in serum fatty acids, glycerophospholipids, and bile acid metabolites. Transcriptomics further revealed that the AMPK and PPAR signalling pathways were critically involved in the regulation of lipid metabolism by which CFE alleviated MAFLD. Consistently, CFE treatment resulted in significant upregulation of AMPK and PPARα expression (p < 0.001) and downregulation of CD36 and DPP4 (p < 0.001), as confirmed by Western blotting and qPCR. Furthermore, integration of WGCNA and network pharmacology pinpointed chlorogenic acid (CA), ursolic acid (UA), and oleanolic acid (OA) as the primary bioactive components, and their lipid-lowering effects were validated in FFA-treated THLE-2 cells. In conclusion, this study offers preliminary insights into the lipid-lowering mechanisms of CFE via regulation of the AMPK/PPARα/CD36/DPP4 signalling pathway and support its further development as a functional food ingredient for MAFLD prevention. Full article

Obesity has emerged as a significant global public health challenge, yet the clinical utility of existing anti-obesity drugs is often constrained by limited efficacy and adverse safety profiles. Rheum tanguticum Maxim. ex Balf., a traditional medicinal plant, has shown potential in modulating glucose and lipid metabolism; however, its specific anti-obesity mechanisms remain poorly characterized. In this study, the chemical profile of the 60% ethanol-eluted fraction of R. tanguticum (RTE) was characterized via UPLC-QTOF/MS, followed by network pharmacology analysis to predict regulatory targets and enriched pathways. Subsequently, a high-fat diet (HFD)-induced obese mouse model was established to evaluate the anti-obesity effects of RTE by monitoring body weight, Lee’s index, fat-to-body weight ratio, serum lipid profiles, and liver histopathological changes. A total of 14 major compounds, primarily anthraquinone glycosides, were identified. Integrated network analysis identified 10 hub targets, including TNF, EGFR, and TP53. In vivo experiments demonstrated that RTE significantly attenuated body weight gain and reduced Lee’s index, fat-to-body ratios, and serum levels of TC, TG, and LDL-C. Furthermore, RTE treatment markedly alleviated hepatic steatosis and inflammatory infiltration in obese mice. These findings suggest that RTE exerts potent anti-obesity effects through a multi-target and multi-pathway mechanism that regulates lipid metabolism and suppresses inflammation. This study improves our understanding of the pharmacological value of R. tanguticum and provides a scientific basis for its development as a functional food ingredient or therapeutic agent against obesity. Full article

The influenza A virus (IAV) has been responsible for multiple seasonal epidemics and poses a pandemic threat, and the growing number of variant strains constitutes a persistent threat to humanity. This study aimed to identify anti-influenza compounds from a traditional Chinese medicine (TCM) monomer library using a machine learning approach, with calmodulin as a hypothesis-driven target. The antiviral efficacy of the compounds with the highest predicted binding scores from virtual screening was evaluated using integrated computational and experimental approaches. A pre-trained protein language model (ConPLex) was employed for virtual screening. Molecular docking was used to predict binding characteristics, and network pharmacology was applied to generate hypotheses on multi-target mechanisms. The cytotoxicity and anti-H1N1 activity of the selected compounds were assessed in vitro, followed by in vivo evaluation of survival, lung pathology, viral load, and inflammatory mediators in a lethal mouse infection model. Sodium deoxycholate (NaDC) and deoxycholic acid (DCA) were identified as promising lead compounds. Both exhibited dose-dependent inhibition of viral replication in vitro with low cytotoxicity. Treatment with NaDC and DCA significantly improved survival rates and reduced lung pathology in H1N1-infected mice. Treatment was associated with suppression of nuclear factor kappa-B (NF-κB) activation, reduced pro-inflammatory cytokines, and elevated interleukin-10 (IL-10) levels. Molecular docking predictions indicated that NaDC and DCA exhibit moderate binding affinity for calmodulin, with binding energies of −8.38 kcal/mol and −7.61 kcal/mol, respectively. Furthermore, network pharmacology analysis suggested that these compounds may modulate pathways related to viral infection, inflammation, and immune regulation. NaDC and DCA demonstrate anti-influenza activity both in vitro and in vivo, reducing viral replication and alleviating inflammatory lung injury. These findings position NaDC and DCA as promising lead compounds for anti-influenza drug development and provide a foundation for further mechanistic validation. Full article

With the increasing demand for sustainable animal production, the utilization of agricultural and processing by-products as functional feed ingredients has gained growing attention. However, the application of Xiasangju processing residues, a by-product generated during the industrial processing of the traditional Chinese herbal formula Xiasangju, in poultry nutrition remains poorly understood. This study aimed to evaluate the nutritional composition, bioactive components, and potential functional effects of Xiasangju processing by-products as a dietary supplement for late-laying hens. Chemical composition was characterized using LC-MS and conventional nutritional analysis, while potential anti-inflammatory mechanisms were predicted via network pharmacology. A total of 288 Jingfen laying hens (55 weeks old) were randomly assigned to four dietary treatments supplemented with 0, 0.5%, 1.0%, or 1.5% Xiasangju processing by-products for 56 days. Results showed that 11 major active compounds were identified, including relatively high levels of linarin and rosmarinic acid, along with abundant crude protein, fiber, minerals, and amino acids. Dietary supplementation at 1.5% was associated with higher egg production rate, egg weight, and yolk color without obvious adverse effects on organ indices or serum biochemical parameters. This treatment was also associated with lower inflammatory gene expression, including IL-6 and COX-2 in the ileum and NF-κB, IL-6, COX-2, and TNF-α in the cecum. No significant effects were observed on antioxidant status in yolk or liver, or intestinal morphology. Integrated analyses using network pharmacology, molecular docking, and in vitro COX-2 inhibition suggested that anti-inflammatory-related responses may involve COX-2-related pathways, while 16S rRNA sequencing indicated changes in gut microbiota composition. In conclusion, Xiasangju processing by-products may serve as a potential functional feed ingredient for late-laying hens, with 1.5% inclusion showing favorable overall performance under the conditions of this study. These effects may be associated with the combined contribution of residual nutrients and bioactive compounds in the residues. Full article

Background: Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus. EJPs (Erjing Pills) are believed in Traditional Chinese Medicine to have the effects of a nourishing essence and a brightening of the eyes, but the specific effect on DR remains unclear. This study aims to investigate the therapeutic effects and underlying mechanisms of EJPs on DR. Methods: The chemical profile of EJPs was characterized by UHPLC-MS. Network pharmacology and molecular docking were employed to predict its active ingredients and potential targets. A DR rat model was induced by streptozotocin. Retinal morphology and function were assessed by OCT, FFA, and H&E staining. The expressions of proteins and mRNAs related to the AGE-RAGE pathway, oxidative stress, inflammation, and tight junctions were detected by Western blot, qPCR, and ELISA. Results: LC-MS and network pharmacology analysis identified 638 common targets between EJPs and DR, with core targets including SRC, AKT1, and MAPK1, primarily enriched in the AGE-RAGE signaling pathway. Molecular docking confirmed strong binding (binding energy < −5.0 kcal/mol) between key EJP constituents and core targets. In vivo, EJP treatment significantly alleviated retinal vascular leakage, improved retinal thickness, and alleviated histopathological damage. In addition, EJPs downregulated the AGEs-RAGE/NF-κB axis and pro-inflammatory cytokines while enhancing antioxidant defenses and tight junction proteins in the retinas of DR rats. Conclusions: EJPs ameliorate DR by protecting the blood–retinal barrier and modulating the AGE-RAGE/oxidative stress/inflammation network, demonstrating a multi-component, multi-target, and multi-pathway mechanism. This study provides a mechanistic basis for the potential application of EJPs in DR management. Full article