Targeting the AGE-RAGE/NF-κB Pathway: An Integrative Study Decoding the Anti-Colitis Effect of Five-Flavor Sophora Flavescens Enteric-Coated Capsule
Abstract
1. Introduction
2. Material and Methods
2.1. Reagents
2.2. Network Pharmacology Analysis
2.3. Animals and Experimental Design
2.4. ELISA
2.5. HE Staining
2.6. IHC Staining
2.7. Western Blot
2.8. qRT-PCR
2.9. Cell Culture and Viability Assay
2.10. Nitric Oxide (NO) Assay
2.11. Patient Grouping
2.12. Clinical Data Collection and Analysis
2.13. Clinical Efficacy Evaluation
2.14. Statistical Analysis
3. Results
3.1. Network Pharmacology Analysis
3.1.1. Identification of Putative Targets for FSEC and UC
3.1.2. Identification of FSEC-UC Targets and Screening of Core Genes
3.1.3. GO Analysis and KEGG Pathway Enrichment Analysis
3.2. Therapeutic Effects of FSEC on UC in Mice
3.2.1. FSEC Ameliorates DSS-Induced Colitis in Mice
3.2.2. FSEC Attenuates Cytokine Expression in the Colon and Serum of DSS-Induced Mice
3.2.3. FSEC Attenuates UC-Induced Inflammation via Modulation of the AGE-RAGE/NF-κB Signaling Pathway
3.3. FSEC Ameliorates Macrophage Inflammation via the AGE-RAGE/NF-κB Pathway
3.4. Efficacy and Safety of FSEC in the Treatment of Mild-to-Moderate UC
3.4.1. Baseline Characteristics
3.4.2. Clinical Remission Rates and Mucosal Healing Rates
3.4.3. Interobserver Agreement Analysis
3.4.4. Statistical Robustness Analyses for Primary Comparisons
3.4.5. Comparison of Laboratory Parameters Related to UC at Baseline and After Treatment
3.4.6. Changes in Laboratory Parameters Related to UC at Baseline and After Treatment
3.4.7. Adverse Events
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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| Variables | FSEC Group (n = 30) | MECT Group (n = 30) | CTFM Group (n = 30) | p Value |
|---|---|---|---|---|
| Age (years) | 47.23 ± 15.55 | 50.57 ± 16.33 | 54.07 ± 16.96 | 0.27 |
| Gender-male (n) | 17 | 15 | 20 | 0.42 |
| Duration of UC (month) | 24.00 (9.50, 44.50) | 24.00 (1.00, 61.75) | 27.00 (2.00, 93.75) | 0.68 |
| BMI | 21.70 (19.58, 22.75) | 21.85 (20.43, 23.65) | 21.64 (20.40, 23.68) | 0.82 |
| Non-smoker (n) | 23 | 29 | 25 | 0.08 |
| No EIMs (n) | 26 | 26 | 25 | 0.91 |
| Disease extent (n) | 0.07 | |||
| E1 | 5 | 10 | 2 | |
| E2 | 10 | 12 | 13 | |
| E3 | 15 | 8 | 15 | |
| Clinical course (n) | 0.22 | |||
| First episode | 6 | 12 | 8 | |
| Chronic continuous | 24 | 18 | 22 | |
| Severity (n) | 0.18 | |||
| Mild | 14 | 16 | 8 | |
| Moderate | 16 | 14 | 21 |
| Parameter | FSEC Group (n = 30) | MECT Group (n = 30) | CTFM Group (n = 30) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Pre | Post | p | Pre | Post | p | Pre | Post | p | |
| WBC | 6.17 ± 1.76 | 6.53 ± 2.77 | 0.49 | 6.46 ± 2.01 | 5.77 ± 1.35 | <0.05 | 7.02 ± 2.65 | 6.51 ± 1.84 | 0.28 |
| NE | 3.77 ± 1.26 | 3.86 ± 2.11 | 0.81 | 3.62 ± 1.46 | 3.60 ± 0.96 | 0.95 | 4.45 ± 2.00 | 4.13 ± 1.75 | 0.27 |
| RBC | 4.36 ± 0.45 | 4.45 ± 0.38 | 0.34 | 4.47 ± 0.59 | 4.57 ± 0.53 | 0.31 | 4.25 ± 0.46 | 4.43 ± 0.63 | 0.10 |
| HB | 127.13 ± 15.73 | 128.63 ± 10.94 | 0.51 | 132.50 ± 17.99 | 135.43 ± 15.15 | 0.15 | 122.00 ± 16.82 | 126.10 ± 10.04 | 0.052 |
| PLT | 250.77 ± 54.73 | 283.07 ± 54.58 | <0.05 | 241.86 ± 61.81 | 248.62 ± 58.73 | 0.94 | 265.70 ± 73.90 | 270.03 ± 67.18 | 0.71 |
| CRP | 8.14 ± 6.91 | 4.90 ± 5.15 | <0.05 | 5.63 ± 4.78 | 3.77 ± 3.26 | <0.05 | 21.89 ± 34.68 | 8.47 ± 12.58 | <0.05 |
| ESR | 17.07 ± 16.61 | 8.60 ± 5.74 | <0.05 | 15.62 ± 11.79 | 9.14 ± 7.94 | <0.05 | 24.60 ± 24.85 | 15.76 ± 18.88 | <0.05 |
| ALB | 39.31 ± 3.38 | 41.00 ± 2.16 | <0.05 | 39.73 ± 3.48 | 41.65 ± 2.64 | <0.05 | 36.62 ± 5.74 | 39.89 ± 3.55 | <0.05 |
| Parameter | FSEC Group (n = 30) | MECT Group (n = 30) | CTFM Group (n = 30) | p |
|---|---|---|---|---|
| WBC | −0.49 (−1.14, 0.82) | 0.65 (−0.54, 1.49) | 0.08 (−1.07, 1.35) | 0.22 |
| NE | −0.05 (−0.58.1.10) | −0.24 (−0.91, 0.50) | 0.33 (−0.72, 1.36) | 0.53 |
| RBC | −0.09 ± 0.50 | −0.09 ± 0.54 | −0.17 ± 0.56 | 0.80 |
| HB | −1.50 ± 12.27 | −2.48 ± 10.80 | −4.10 ± 11.06 | 0.68 |
| PLT | −29.5 (−61.00, −1.75) | −8.00 (−30.50, 33.00) | −13.50 (−38.75, 41.00) | 0.05 |
| CRP | 3.24 ± 6.11 | 1.85 ± 3.55 | 13.41 ± 24.46 | <0.05 |
| ESR | 5.00 (0.00, 12.25) | 6.00 (1.50, 11.35) | 4.50 (−0.25, 23.00) | 0.98 |
| ALB | −1.69 ± 3.64 | −1.91 ± 3.09 | −3.26 ± 5.49 | 0.32 |
| Gene Name | Full Name | Main Functions | Correlation with UC |
|---|---|---|---|
| ICAM1 [31] | Intercellular Adhesion Molecule-1 | It mediates leukocyte adhesion and transmigration across the endothelium. | Alicaforsen, an antisense oligonucleotide targeting ICAM-1, has been evaluated in clinical trials for UC, although with limited efficacy as a systemic therapy. |
| CXCL2 [32] | C-X-C motif chemokine | A potent chemoattractant directing neutrophil migration to sites of inflammation. | Identified as a genetic risk marker in IBD transcriptome analysis, suggesting involvement in neutrophil-driven intestinal inflammation. |
| HMOX1 [33] | Heme Oxygenase 1 | A cytoprotective enzyme that degrades heme into antioxidant products, exerting anti-inflammatory and anti-apoptotic effects. | Modulates intestinal inflammation by protecting colonic mucosa from oxidative injury; its pharmacological activation attenuates experimental colitis. |
| F3 [34,41] | Coagulation factor III (Tissue factor) | Activation of the extrinsic coagulation pathway may contribute to local microthrombus formation, exacerbating mucosal injury. | TF-dependent PAR-2 activation in colonic epithelial cells leads to local keratinocyte-derived chemokine production, triggering granulocyte influx, leading to inflammation and organ damage. |
| THBD [35,42] | Thrombomodulin | Glycomembrane protein and activator protein C system in vascular endothelial cells exert anticoagulant, anti-inflammatory, and endothelial protective effects. | It was significantly increased in patients with active IBD. It may play a regulatory role in fibrin deposition in inflammatory sites and/or in the progression of inflammatory processes. |
| PLAU [36] | Plasminogen activator, urokinase | Protein-coding genes convert plasminogen into plasmin. Involved in tumor cell invasion and metastasis. | PLAU is one of the potential therapeutic targets predicted by network pharmacology. |
| SLC6A4 [37,43] | Solute carrier family 6-member 4 | It encodes serotonin transporter (SERT), regulates 5-hydroxytryptamine reuptake and affects the function of ‘brain-gut axis’. | 5-HT inhibits intestinal inflammation through the 5-HT7R/RIPK1 pathway |
| MAOB [44] | Monoamine oxidase B | Metabolize monoamine neurotransmitters such as 5-hydroxytryptamine and dopamine | To control 5-HT degradation by regulating MAOB activity, attention should be paid to avoid excessive accumulation of 5-HT caused by MAOB inhibition. |
| DPP4 [38] | Dipeptidyl peptidase 4 | A serine protease, widely involved in blood glucose regulation, immune response and cell signal transduction. | IBD potential biomarkers, its inhibitors significantly reduce colonic inflammation by inhibiting GLP-2 degradation. DPP4 gene knockout induces different outcomes in different species, indicating the complexity of DPP4 function. |
| CYP3A4 [39] | Cytochrome P450 3A4 | It is an important member of the cytochrome P450 enzyme system, mainly involved in drug metabolism, and its expression is decreased in the inflammatory state. | Intestinal inflammation inhibits the expression of intestinal P450 and changes the pharmacokinetics of some drugs. |
| APOB [40] | Apolipoprotein B | The main structural proteins of low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) are responsible for lipid transport and metabolism. | Given that UC is often accompanied by dyslipidemia, impaired APOB function may disrupt intestinal lipid absorption or transport, thereby exacerbating inflammation. |
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Hu, B.; Wang, X.; Chen, X.; Li, T.; Li, C.; Zhang, Y.; Wang, Y.; Mao, J. Targeting the AGE-RAGE/NF-κB Pathway: An Integrative Study Decoding the Anti-Colitis Effect of Five-Flavor Sophora Flavescens Enteric-Coated Capsule. Biomedicines 2026, 14, 1236. https://doi.org/10.3390/biomedicines14061236
Hu B, Wang X, Chen X, Li T, Li C, Zhang Y, Wang Y, Mao J. Targeting the AGE-RAGE/NF-κB Pathway: An Integrative Study Decoding the Anti-Colitis Effect of Five-Flavor Sophora Flavescens Enteric-Coated Capsule. Biomedicines. 2026; 14(6):1236. https://doi.org/10.3390/biomedicines14061236
Chicago/Turabian StyleHu, Baihui, Xiaocong Wang, Xiuli Chen, Tong Li, Chuqiao Li, Yapu Zhang, Yingde Wang, and Jingwei Mao. 2026. "Targeting the AGE-RAGE/NF-κB Pathway: An Integrative Study Decoding the Anti-Colitis Effect of Five-Flavor Sophora Flavescens Enteric-Coated Capsule" Biomedicines 14, no. 6: 1236. https://doi.org/10.3390/biomedicines14061236
APA StyleHu, B., Wang, X., Chen, X., Li, T., Li, C., Zhang, Y., Wang, Y., & Mao, J. (2026). Targeting the AGE-RAGE/NF-κB Pathway: An Integrative Study Decoding the Anti-Colitis Effect of Five-Flavor Sophora Flavescens Enteric-Coated Capsule. Biomedicines, 14(6), 1236. https://doi.org/10.3390/biomedicines14061236

