The Flavonoid Extract of Polygonum viviparum L. Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Regulating Intestinal Flora Homeostasis and Uric Acid Levels Through Inhibition of PI3K/AKT/NF-κB/IL-17 Signaling Pathway
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Preparation and Identification of TFPV
2.3. Cell Culture
2.4. Cell Viability Assay and Establishment of LPS-Induced Inflammatory Model in IPEC-J2 Cells
2.5. Animals
2.6. Establishment of LPS-Induced Intestinal Inflammation Model in Mice
2.7. Network Pharmacology Analysis
2.8. Establishment of Ulcerative Colitis Model in Mice
2.9. Histopathological Evaluation
2.10. Enzyme-Linked Immunosorbent (ELISA) Assay
2.11. Immunohistochemical (IHC) Analysis
2.12. RNA Extraction and Quantitative Real-Time PCR Analysis (RT-qPCR)
2.13. Western Blotting Analysis
2.14. 16S rRNA Gene-Based Microbial Community Analysis
2.15. Metabolomic Analysis
2.16. Statistical Analysis
3. Results
3.1. Identification of Components in TFPV
3.2. TFPV Can Effectively Alleviate Inflammation of LPS-Induced IPEC-J2 Cells
3.3. TFPV Improves LPS-Induced Intestinal Inflammation in Mice by Enhancing the Intestinal Barrier Function
3.4. Targets Prediction of TFPV for UC by Network Pharmacology
3.5. TFPV Alleviates DSS-Induced UC in Mice by Regulating Intestinal Inflammatory Levels and Enhancing Intestinal Barrier Function
3.6. TFPV Enhances the Diversity of the Intestinal Microbiota and Reverses the DSS-Induced Dysbiosis in Mice
3.7. TFPV Regulates Purine Metabolism and Reduces Uric Acid Levels in Mice with DSS-Induced UC
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
| ADP | Adenosine Diphosphate |
| AKT | Protein Kinase B |
| BP | Biological Processes |
| CC | Cellular Components |
| DAI | Disease Activity Index |
| dGMP | 2′-Deoxyguanosine 5′-Monophosphate |
| DSS | Dextran sulfate sodium |
| ELISA | Enzyme-Linked Immunosorbent |
| FC | Fold Change |
| H&E | Hematoxylin and Eosin |
| IBD | Inflammatory Bowel Disease |
| IHC | Immunohistochemical |
| IL-6 | Interleukin-6 |
| IL-10 | Interleukin-10 |
| IL-1β | Interleukin-1 Beta |
| IL-17 | Interleukin-17 |
| LPS | Lipopolysaccharide |
| LC-MS | Liquid Chromatography-Mass Spectrometry |
| MF | Molecular Functions |
| MAPK | Mitogen-Activated Protein Kinase |
| NF-κB | Nuclear Factor-κB |
| OPLS-DA | Orthogonal Projections to Latent Structures-Discriminant Analysis |
| PI3K | Phosphatidylinositol 3-Kinase |
| RT-qPCR | RNA Extraction And Quantitative Real-Time PCR Analysis |
| TFPV | Total Flavonoids of Polygonum viviparum L. |
| TJ | Tight Junctions |
| TNF-α | Tumor Necrosis Factor Alpha |
| UA | Uric Acid |
| UC | Ulcerative Colitis |
| VIP | Variable Importance In Projection |
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| Gene | Primer Sequences (5′ to 3′) | Fragment Size (bp) | |
|---|---|---|---|
| β-actin | Forward | TTCTAGGCGGACTTGCAGC | 128 |
| Reverse | GCTTCTCAGCAGACAGGAGG | ||
| Claudin-1 | Forward | TCTTTCTTATTTCAGGTCTGGCT | 91 |
| Reverse | ACTGGGGTCATGGGGTCATA | ||
| Occludin | Forward | CAGGTGCACCCTCCAGATTG | 111 |
| Reverse | TGGACTTTCAAGAGGCCTGG | ||
| ZO-1 | Forward | GAAATACCTGACGGTGCTGC | 99 |
| Reverse | GAGGATGGCGTTACCCACAG | ||
| IL-6 | Forward | AAGCTGCAGTCACAGAACGA | 136 |
| Reverse | TGGACGGCATCAATCTCAGG | ||
| IL-10 | Forward | CGGCCCAGTGAAGAGTTTCT | 98 |
| Reverse | GGCAACCCAGGTAACCCTTA | ||
| IL-1β | Forward | CCAATTCAGGGACCCTACCC | 174 |
| Reverse | GTTTTGGGTGCAGCACTTCAT | ||
| TNF-α | Forward | GGCCCAAGGACTCAGATCAT | 82 |
| Reverse | CTGTCCCTCGGCTTTGACAT | ||
| NO | Name | Formula | Mass (Da) | [M-H]- | Error (ppm) | Rt (min) |
|---|---|---|---|---|---|---|
| 1 | DTXSID601174808 | C16H23NO9S2 | 437.49 | 436.07 | 1.18 | 0.645 |
| 2 | N2-(1-Deoxy-I(2)-D-fructopyranos-1-yl)-L-arginine | C12H24N4O7 | 336.34 | 335.15 | 1.6 | 0.662 |
| 3 | Cotinine N-glucuronide | C16H20N2O7 | 352.34 | 351.12 | 2.6 | 1.062 |
| 4 | beta-Glucogallin | C13H16O10 | 332.26 | 331.06 | 0.9 | 1.508 |
| 5 | Erioflorin methacrylate | C25H22FNO3 | 403.45 | 402.15 | 1 | 1.913 |
| 6 | Esculin * | C15H16O9 | 340.28 | 339.07 | 1.18 | 2.551 |
| 7 | Pentoxifylline | C13H18N4O3 | 278.31 | 277.13 | 0.6 | 3.36 |
| 8 | Kaempferin * | C21H20O10 | 432.38 | 431.09 | 0.7 | 4.201 |
| 9 | Gallic acid | C7H6O5 | 170.12 | 169.01 | 0.5 | 5.273 |
| 10 | Luteolin * | C15H10O6 | 286.23 | 285.04 | 0.71 | 5.146 |
| 11 | Bispyribac | C19H18N4O8 | 430.37 | 429.10 | 0.79 | 5.991 |
| 12 | Procodazole | C10H10N2O2 | 190.2 | 189.07 | 0.8 | 6.285 |
| 13 | Galangin * | C15H10O5 | 270.24 | 269.05 | 0.8 | 6.514 |
| 14 | Querciturone * | C21H18O13 | 478.36 | 477.07 | 0.08 | 7.635 |
| 15 | Paucin | C23H32O10 | 468.49 | 467.19 | 0.1 | 9.163 |
| 16 | Melanoxetin * | C15H10O7 | 302.24 | 301.03 | 0.18 | 9.878 |
| 17 | Tetradecanoic acid | C14H28O2 | 228.37 | 227.20 | 0.3 | 10.49 |
| 18 | DTXSID401101613 | C44H64O16 | 848.97 | 847.41 | 0.32 | 11.529 |
| 19 | Hexadecanamide | C16H33NO | 255.44 | 254.25 | 0.5 | 12.169 |
| 20 | Furanodiene | C15H20O | 216.32 | 215.14 | 0.2 | 14.889 |
| 21 | Acrovestone | C32H42O8 | 554.67 | 553.28 | 0.22 | 15.832 |
| 22 | 10-Gingerol | C21H34O4 | 350.49 | 349.28 | 0.25 | 16.734 |
| 23 | L-Ascorbyl 6-Stearate | C24H42O7 | 442.59 | 441.28 | 0.27 | 18.252 |
| 24 | Stearyl citrate | C24H46O8 | 462.62 | 461.31 | 0.63 | 19.631 |
| 25 | Misoprostol acid | C21H36O5 | 368.51 | 367.25 | 0.45 | 21.257 |
| 26 | (6S,7R)-2-azaspiro [5.5] undecan-7-ol | C10H19NO | 169.26 | 168.14 | 0.68 | 21.635 |
| 27 | Phorbol 12-tiglate 13-decanoate | C35H52O8 | 600.78 | 599.36 | 0.4 | 22.949 |
| 28 | Irehine | C23H39NO | 345.56 | 344.29 | 0.69 | 23.265 |
| 29 | beta-Sitosterol | C29H50O | 414.73 | 413.38 | 0.27 | 25.321 |
| 30 | 1,1′-(1,4-Dihydro-4-nonyl-3,5-pyridinediyl) bis [1-decanone] | C34H61NO2 | 515.85 | 514.46 | 0.31 | 25.739 |
| 31 | Uvaricin | C39H68O7 | 648.95 | 647.49 | 1 | 27.043 |
| 32 | 1,2-Di-O-palmitoyl-3-O-(6-sulfoquinovopyranosyl) glycerol | C41H78O12S | 795.12 | 793.51 | 0.32 | 27.13 |
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Liu, H.; Yang, Z.; Chen, Q.; Zhang, H.; Liu, Y.; Wu, D.; Shao, D.; Wang, S.; Hao, B. The Flavonoid Extract of Polygonum viviparum L. Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Regulating Intestinal Flora Homeostasis and Uric Acid Levels Through Inhibition of PI3K/AKT/NF-κB/IL-17 Signaling Pathway. Antioxidants 2025, 14, 1206. https://doi.org/10.3390/antiox14101206
Liu H, Yang Z, Chen Q, Zhang H, Liu Y, Wu D, Shao D, Wang S, Hao B. The Flavonoid Extract of Polygonum viviparum L. Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Regulating Intestinal Flora Homeostasis and Uric Acid Levels Through Inhibition of PI3K/AKT/NF-κB/IL-17 Signaling Pathway. Antioxidants. 2025; 14(10):1206. https://doi.org/10.3390/antiox14101206
Chicago/Turabian StyleLiu, Haoyu, Zhen Yang, Qian Chen, Hongjuan Zhang, Yu Liu, Di Wu, Dan Shao, Shengyi Wang, and Baocheng Hao. 2025. "The Flavonoid Extract of Polygonum viviparum L. Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Regulating Intestinal Flora Homeostasis and Uric Acid Levels Through Inhibition of PI3K/AKT/NF-κB/IL-17 Signaling Pathway" Antioxidants 14, no. 10: 1206. https://doi.org/10.3390/antiox14101206
APA StyleLiu, H., Yang, Z., Chen, Q., Zhang, H., Liu, Y., Wu, D., Shao, D., Wang, S., & Hao, B. (2025). The Flavonoid Extract of Polygonum viviparum L. Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Regulating Intestinal Flora Homeostasis and Uric Acid Levels Through Inhibition of PI3K/AKT/NF-κB/IL-17 Signaling Pathway. Antioxidants, 14(10), 1206. https://doi.org/10.3390/antiox14101206

