ORIGINAL RESEARCH article
Front. Immunol.
Sec. Mucosal Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1623080
This article is part of the Research TopicNatural Constituents and Mucosal Immunity: Immune Protection and Treatment of Mucosal Barriers and Microbial Flora Using Omics Technologies and Gene SequencingView all 13 articles
Network pharmacology to explore the novel anti-inflammatory mechanism of naringenin in intestinal ischemia/reperfusion injury
Provisionally accepted- 1Lanzhou University, Lanzhou, China
- 2lanzhou, gansu, China
- 3Liaocheng Hospital of Chinese Medicine, shandong, China
- 4Taian City Central Hospital, shandong, China
- 5Taian City Central Hospital, shandsong, China
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Naringenin (Nar), a common flavanone abundant in citrus fruits and tomatoes, is common in diets. Although Nar can alleviate intestinal ischemia/reperfusion injury (IRI), the exact anti-inflammatory mechanisms are unclear and require further study.In this study, we employed a comprehensive research strategy that integrated network pharmacology analysis with both in vitro and in vivo experimental validations to systematically elucidate Nar's anti-inflammatory mechanisms in intestinal IRI. Network pharmacology uncovered 88 common anti-inflammatory targets for Nar in intestinal IRI. Among these, TNF, IL6, AKT1, IL1B, TP53, STAT3, and PTGS2 were identified as hub genes. Validation experiments demonstrated that Nar induced anti-inflammatory responses through downregulating calprotectin, IL-1β, IL-6, and TNF-α, while promoting IL-10 secretion. Additionally, Nar pretreatment significantly downregulated PTGS2 and phosphorylated STAT3 (p-STAT3). Further mechanistic investigations were conducted using the YAP inhibitor verteporfin (VP) in vitro and in vivo. Nar pretreatment activated YAP, thereby enhancing its anti-inflammatory effects. Conversely, inhibiting YAP activation with VP increased p-STAT3 and enhanced inflammatory responses, diminishing Nar's efficacy. This study demonstrated that Nar inhibited intestinal inflammatory responses by activating YAP, which suppressed p-STAT3 expression, and provided a theoretical basis for Nar's clinical application in intestinal IRI.
Keywords: Intestinal ischemia/reperfusion injury, Network Pharmacology, Naringenin, Inflammation, YAP, stat3
Received: 05 May 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 Hou, Wang, Tan, Liu, Li, Han, Leng and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Min Hou, Lanzhou University, Lanzhou, China
Yufang Leng, Lanzhou University, Lanzhou, China
Zaiqi Yang, Taian City Central Hospital, shandong, China
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