Integrative network pharmacology, machine learning, and experimental validation reveal the protective potential and potential molecular mechanisms of orientin in DSS-induced colitis
4 affiliations
- 1Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000, People's Republic of China; Department of Gastrointestinal Surgery, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, 434020, People's Republic of China
- 2Department of Pharmacy, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, 434020, People's Republic of China
- 3Department of Gastrointestinal Surgery, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, 434020, People's Republic of China
- 4Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000, People's Republic of China; Corresponding author.
Abstract
Background: Ulcerative colitis (UC) is a chronic and recurring inflammatory disease affecting the colonic epithelium. Orientin, a natural flavonoid C-glycoside, shows various anti-inflammatory and antioxidant properties. However, the effects of orientin on UC and the related molecular mechanisms have not been thoroughly studied. Methods: UC-related genes were identified from GeneCards, OMIM, and TTD and analyzed using the GSE87466 dataset, followed by GO and KEGG enrichment analyses. Four machine-learning algorithms were applied to identify candidate targets. Molecular docking and 100-ns molecular dynamics simulations followed by MM-PBSA binding free-energy analysis were performed for the identified target–Orientin complexes. ROC was used to evaluate model performance. In vivo, DSS-induced colitis mice were treated orally with Orientin (10 mg/kg/day), and disease severity, histopathological changes, target gene expression, and pro-inflammatory cytokines were evaluated. Results: Four central targets, such as ABCB1, PPARGC1A, FAP and LYN, were selected by all the machine learning techniques. The AUC values of the four-gene model in the training set and the validation set were all greater than 0.8. In vivo experiments show that Orientin can considerably attenuate DSS-induced weight loss, reduce the Disease Activity Index (DAI), reverse DSS-induced colon shortening and decrease the histopathological damage caused by DSS. Additionally, Orientin can restore the abnormal mRNA levels of ABCB1, PPARGC1A, FAP and LYN. It can also decrease the high mRNA expression levels of IL - 6, IL - 1β and TNF-α in the colonic tissues, which are induced by DSS. Conclusion: The results of this study show that Orientin has protective effects on colitis caused by DSS via a multi-target regulatory process. ABCB1 and PPARGC1A may represent important candidate targets of Orientin.
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BibTeX
@article{zeng2026integrative,
title = {{Integrative network pharmacology, machine learning, and experimental validation reveal the protective potential and potential molecular mechanisms of orientin in DSS-induced colitis}},
author = {Fang Zeng and Danyun Wei and Zilong Zhang and Lei Zhou and Yongbin Zheng},
journal = {Journal of Radiation Research and Applied Sciences},
year = {2026},
month = oct,
doi = {10.1016/j.jrras.2026.102779},
url = {https://doi.org/10.1016/j.jrras.2026.102779},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrative network pharmacology, machine learning, and experimental validation reveal the protective potential and potential molecular mechanisms of orientin in DSS-induced colitis
AU - Fang Zeng
AU - Danyun Wei
AU - Zilong Zhang
AU - Lei Zhou
AU - Yongbin Zheng
PY - 2026
DA - 2026/10/30
JO - Journal of Radiation Research and Applied Sciences
DO - 10.1016/j.jrras.2026.102779
UR - https://doi.org/10.1016/j.jrras.2026.102779
AB - Background: Ulcerative colitis (UC) is a chronic and recurring inflammatory disease affecting the colonic epithelium. Orientin, a natural flavonoid C-glycoside, shows various anti-inflammatory and antioxidant properties. However, the effects of orientin on UC and the related molecular mechanisms have not been thoroughly studied. Methods: UC-related genes were identified from GeneCards, OMIM, and TTD and analyzed using the GSE87466 dataset, followed by GO and KEGG enrichment analyses. Four machine-learning algorithms were applied to identify candidate targets. Molecular docking and 100-ns molecular dynamics simulations followed by MM-PBSA binding free-energy analysis were performed for the identified target–Orientin complexes. ROC was used to evaluate model performance. In vivo, DSS-induced colitis mice were treated orally with Orientin (10 mg/kg/day), and disease severity, histopathological changes, target gene expression, and pro-inflammatory cytokines were evaluated. Results: Four central targets, such as ABCB1, PPARGC1A, FAP and LYN, were selected by all the machine learning techniques. The AUC values of the four-gene model in the training set and the validation set were all greater than 0.8. In vivo experiments show that Orientin can considerably attenuate DSS-induced weight loss, reduce the Disease Activity Index (DAI), reverse DSS-induced colon shortening and decrease the histopathological damage caused by DSS. Additionally, Orientin can restore the abnormal mRNA levels of ABCB1, PPARGC1A, FAP and LYN. It can also decrease the high mRNA expression levels of IL - 6, IL - 1β and TNF-α in the colonic tissues, which are induced by DSS. Conclusion: The results of this study show that Orientin has protective effects on colitis caused by DSS via a multi-target regulatory process. ABCB1 and PPARGC1A may represent important candidate targets of Orientin.
SN - 2314-7164
SN - 1687-8507
ER -