Huoshan Dendrobium Zengye Jiedu Formula mitigates radiation-induced oral mucositis and improves oral immune microenvironment by targeting the EGFR/PI3K/AKT pathway: evidence from network pharmacology, molecular docking, and experimental validation

IntroductionRadiation-induced oral mucositis (RIOM) manifests as mucosal ulceration, pain, and dysphagia, disrupting treatment and quality of life. Its pathogenesis involves inflammatory imbalance and immune dysregulation, driven by microbial infiltration and cytokine storms. Current therapies remai...

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Main Authors: Chang Liu, Xinru Liu, Jiabao Liu, Hao Zhang, Pengcheng Zhang, Xingxing Huo, Hang Song, Yongfu Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559400/full
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author Chang Liu
Xinru Liu
Jiabao Liu
Hao Zhang
Pengcheng Zhang
Xingxing Huo
Hang Song
Yongfu Zhu
Yongfu Zhu
Yongfu Zhu
author_facet Chang Liu
Xinru Liu
Jiabao Liu
Hao Zhang
Pengcheng Zhang
Xingxing Huo
Hang Song
Yongfu Zhu
Yongfu Zhu
Yongfu Zhu
author_sort Chang Liu
collection DOAJ
description IntroductionRadiation-induced oral mucositis (RIOM) manifests as mucosal ulceration, pain, and dysphagia, disrupting treatment and quality of life. Its pathogenesis involves inflammatory imbalance and immune dysregulation, driven by microbial infiltration and cytokine storms. Current therapies remain inadequate, necessitating deeper exploration of immune-microbial interactions for effective interventions.MethodsBioactive components of Huoshan Dendrobium Zengye Jiedu Formula (HDZJF) and RIOM-related targets were retrieved from public databases. Core therapeutic targets and pathways were systematically analyzed via protein-protein interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Molecular docking evaluated interactions between HDZJF components and key targets. A rat RIOM model validated HDZJF efficacy by assessing mucositis severity, inflammatory cytokines, and EGFR/PI3K/AKT pathway protein expression.ResultsA total of 102 bioactive components and 379 potential targets for RIOM were identified. GO and KEGG enrichment analyses suggest that HDZJF exerts therapeutic effects on RIOM by modulating processes such as angiogenesis, inflammation, and apoptosis through pathways like PI3K-AKT. Molecular docking confirmed strong binding affinities between HDZJF components and key targets. In vivo, HDZJF reduced inflammation, promoted mucosal healing, improved body weight, and modulated protein expression related to EGFR/PI3K/AKT.DiscussionThe findings highlight HDZJF's capacity to alleviate RIOM by targeting the EGFR/PI3K/AKT pathway, thereby suppressing inflammatory responses and apoptotic processes. These results underscore HDZJF's translational potential for RIOM treatment and justify further clinical investigation into its therapeutic utility.
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spelling doaj-art-bf6c6cf8d65f4760846127a20e2f64f62025-08-20T02:58:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15594001559400Huoshan Dendrobium Zengye Jiedu Formula mitigates radiation-induced oral mucositis and improves oral immune microenvironment by targeting the EGFR/PI3K/AKT pathway: evidence from network pharmacology, molecular docking, and experimental validationChang Liu0Xinru Liu1Jiabao Liu2Hao Zhang3Pengcheng Zhang4Xingxing Huo5Hang Song6Yongfu Zhu7Yongfu Zhu8Yongfu Zhu9The First Clinical Medical College, Anhui University of Chinese Medicine, Hefei, ChinaThe First Clinical Medical College, Anhui University of Chinese Medicine, Hefei, ChinaThe First Clinical Medical College, Anhui University of Chinese Medicine, Hefei, ChinaThe First Clinical Medical College, Anhui University of Chinese Medicine, Hefei, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaExperimental Center of Clinical Research, Scientific Research Department, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, ChinaCollege of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, ChinaThe First Clinical Medical College, Anhui University of Chinese Medicine, Hefei, ChinaDepartment of Oncology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, ChinaGuo-jun Hu Inheritance Talent Training Office, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, ChinaIntroductionRadiation-induced oral mucositis (RIOM) manifests as mucosal ulceration, pain, and dysphagia, disrupting treatment and quality of life. Its pathogenesis involves inflammatory imbalance and immune dysregulation, driven by microbial infiltration and cytokine storms. Current therapies remain inadequate, necessitating deeper exploration of immune-microbial interactions for effective interventions.MethodsBioactive components of Huoshan Dendrobium Zengye Jiedu Formula (HDZJF) and RIOM-related targets were retrieved from public databases. Core therapeutic targets and pathways were systematically analyzed via protein-protein interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Molecular docking evaluated interactions between HDZJF components and key targets. A rat RIOM model validated HDZJF efficacy by assessing mucositis severity, inflammatory cytokines, and EGFR/PI3K/AKT pathway protein expression.ResultsA total of 102 bioactive components and 379 potential targets for RIOM were identified. GO and KEGG enrichment analyses suggest that HDZJF exerts therapeutic effects on RIOM by modulating processes such as angiogenesis, inflammation, and apoptosis through pathways like PI3K-AKT. Molecular docking confirmed strong binding affinities between HDZJF components and key targets. In vivo, HDZJF reduced inflammation, promoted mucosal healing, improved body weight, and modulated protein expression related to EGFR/PI3K/AKT.DiscussionThe findings highlight HDZJF's capacity to alleviate RIOM by targeting the EGFR/PI3K/AKT pathway, thereby suppressing inflammatory responses and apoptotic processes. These results underscore HDZJF's translational potential for RIOM treatment and justify further clinical investigation into its therapeutic utility.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559400/fullradiation-induced oral mucositispharmacological mechanismnetwork pharmacologymolecular dockingexperimental validation
spellingShingle Chang Liu
Xinru Liu
Jiabao Liu
Hao Zhang
Pengcheng Zhang
Xingxing Huo
Hang Song
Yongfu Zhu
Yongfu Zhu
Yongfu Zhu
Huoshan Dendrobium Zengye Jiedu Formula mitigates radiation-induced oral mucositis and improves oral immune microenvironment by targeting the EGFR/PI3K/AKT pathway: evidence from network pharmacology, molecular docking, and experimental validation
Frontiers in Immunology
radiation-induced oral mucositis
pharmacological mechanism
network pharmacology
molecular docking
experimental validation
title Huoshan Dendrobium Zengye Jiedu Formula mitigates radiation-induced oral mucositis and improves oral immune microenvironment by targeting the EGFR/PI3K/AKT pathway: evidence from network pharmacology, molecular docking, and experimental validation
title_full Huoshan Dendrobium Zengye Jiedu Formula mitigates radiation-induced oral mucositis and improves oral immune microenvironment by targeting the EGFR/PI3K/AKT pathway: evidence from network pharmacology, molecular docking, and experimental validation
title_fullStr Huoshan Dendrobium Zengye Jiedu Formula mitigates radiation-induced oral mucositis and improves oral immune microenvironment by targeting the EGFR/PI3K/AKT pathway: evidence from network pharmacology, molecular docking, and experimental validation
title_full_unstemmed Huoshan Dendrobium Zengye Jiedu Formula mitigates radiation-induced oral mucositis and improves oral immune microenvironment by targeting the EGFR/PI3K/AKT pathway: evidence from network pharmacology, molecular docking, and experimental validation
title_short Huoshan Dendrobium Zengye Jiedu Formula mitigates radiation-induced oral mucositis and improves oral immune microenvironment by targeting the EGFR/PI3K/AKT pathway: evidence from network pharmacology, molecular docking, and experimental validation
title_sort huoshan dendrobium zengye jiedu formula mitigates radiation induced oral mucositis and improves oral immune microenvironment by targeting the egfr pi3k akt pathway evidence from network pharmacology molecular docking and experimental validation
topic radiation-induced oral mucositis
pharmacological mechanism
network pharmacology
molecular docking
experimental validation
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559400/full
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