Exploration of the mechanism of Lithospermum erythrorhizon oil in treating atopic dermatitis based on network pharmacology and experimental validation of the PI3K-Akt pathway regulation
Objective: This study aimed to explore the molecular mechanisms of Lithospermum erythrorhizon oil in treating atopic dermatitis (AD), with a particular focus on its regulatory effect on the PI3K-Akt signaling pathway. Methods: Utilizing a network pharmacology approach integrated with experimental va...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844025000878 |
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| author | Weisheng Hu Yinlan Wang Yingjie Zhou Junbao Shi Zengyan Li Xiaoling Jiang Qinyuan Wu Changming Zhong Huilan Weng Sijie Ouyang Yuan Jing Xianxiang Cai Mingda Ye Ning Huang |
| author_facet | Weisheng Hu Yinlan Wang Yingjie Zhou Junbao Shi Zengyan Li Xiaoling Jiang Qinyuan Wu Changming Zhong Huilan Weng Sijie Ouyang Yuan Jing Xianxiang Cai Mingda Ye Ning Huang |
| author_sort | Weisheng Hu |
| collection | DOAJ |
| description | Objective: This study aimed to explore the molecular mechanisms of Lithospermum erythrorhizon oil in treating atopic dermatitis (AD), with a particular focus on its regulatory effect on the PI3K-Akt signaling pathway. Methods: Utilizing a network pharmacology approach integrated with experimental validation, we identified active components and potential targets of Lithospermum erythrorhizon oil via TCMSP, ChemSrc, PubChem, and PharmMapper. Common targets were selected by intersecting these with AD-related targets from GeneCards. A protein-protein interaction (PPI) network was built using STRING, and functional analysis Gene Ontology (GO) and pathway enrichment Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on Metascape. A Gene-miRNA regulatory network was constructed on miRTarBase and NetworkAnalyst, with miRNA functions annotated by miEAA. An AD mouse model induced by DNCB was established to evaluate Lithospermum erythrorhizon oil's therapeutic efficacy, its influence on inflammatory markers, and the PI3K-Akt pathway. Results: Fifteen common targets were found to be crucial in AD pathogenesis. The PPI network, constructed using STRING, revealed interactions among 13 nodes and 42 edges, with Cytoscape analysis highlighting 10 core targets. GO and KEGG analyses were significant in biological processes like cell migration and inflammatory response regulation, and in pathways such as IL-17 signaling and PI3K-Akt signaling. The Gene-miRNA network suggested Lithospermum erythrorhizon oil may regulate miRNAs like hsa-mir-124-3p and hsa-let-7b-5p. Experimental results showed that Lithospermum erythrorhizon oil significantly improved AD symptoms in mice, reduced IL-4 and IL-13 levels, and decreased p-PI3K, p-PI3K/PI3K, p-Akt, and p-Akt/Akt expression, inhibiting PI3K-Akt pathway activation. Conclusion: Lithospermum erythrorhizon oil exerts multi-target, multi-pathway therapeutic effects in AD, potentially through suppressing Th2-mediated immune responses and the PI3K-Akt signaling pathway, suggesting novel avenues for AD treatment strategies. |
| format | Article |
| id | doaj-art-5f6d5f51a2aa401e89731fcdaeb2302a |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Heliyon |
| spelling | doaj-art-5f6d5f51a2aa401e89731fcdaeb2302a2025-02-02T05:28:00ZengElsevierHeliyon2405-84402025-01-01112e41707Exploration of the mechanism of Lithospermum erythrorhizon oil in treating atopic dermatitis based on network pharmacology and experimental validation of the PI3K-Akt pathway regulationWeisheng Hu0Yinlan Wang1Yingjie Zhou2Junbao Shi3Zengyan Li4Xiaoling Jiang5Qinyuan Wu6Changming Zhong7Huilan Weng8Sijie Ouyang9Yuan Jing10Xianxiang Cai11Mingda Ye12Ning Huang13The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, ChinaThe Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, ChinaThe Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, ChinaThe Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, ChinaThe Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, ChinaThe Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, ChinaThe Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, ChinaThe Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, ChinaThe Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, China; Fujian Provincial Key Laboratory for Integrated Traditional Chinese and Western Medicine Dermatology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, ChinaSchool of Acupuncture and Tuina, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, ChinaSchool of Acupuncture and Tuina, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, ChinaThe Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, ChinaThe Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, ChinaThe Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, China; Fujian Provincial Key Laboratory for Integrated Traditional Chinese and Western Medicine Dermatology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350001, China; Corresponding author. Key Laboratory of Dermatology in Integrated Traditional Chinese and Western Medicine, The Second Affiliated Hospital of Fujian Traditional Chinese Medical University, Fujian, ChinaObjective: This study aimed to explore the molecular mechanisms of Lithospermum erythrorhizon oil in treating atopic dermatitis (AD), with a particular focus on its regulatory effect on the PI3K-Akt signaling pathway. Methods: Utilizing a network pharmacology approach integrated with experimental validation, we identified active components and potential targets of Lithospermum erythrorhizon oil via TCMSP, ChemSrc, PubChem, and PharmMapper. Common targets were selected by intersecting these with AD-related targets from GeneCards. A protein-protein interaction (PPI) network was built using STRING, and functional analysis Gene Ontology (GO) and pathway enrichment Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on Metascape. A Gene-miRNA regulatory network was constructed on miRTarBase and NetworkAnalyst, with miRNA functions annotated by miEAA. An AD mouse model induced by DNCB was established to evaluate Lithospermum erythrorhizon oil's therapeutic efficacy, its influence on inflammatory markers, and the PI3K-Akt pathway. Results: Fifteen common targets were found to be crucial in AD pathogenesis. The PPI network, constructed using STRING, revealed interactions among 13 nodes and 42 edges, with Cytoscape analysis highlighting 10 core targets. GO and KEGG analyses were significant in biological processes like cell migration and inflammatory response regulation, and in pathways such as IL-17 signaling and PI3K-Akt signaling. The Gene-miRNA network suggested Lithospermum erythrorhizon oil may regulate miRNAs like hsa-mir-124-3p and hsa-let-7b-5p. Experimental results showed that Lithospermum erythrorhizon oil significantly improved AD symptoms in mice, reduced IL-4 and IL-13 levels, and decreased p-PI3K, p-PI3K/PI3K, p-Akt, and p-Akt/Akt expression, inhibiting PI3K-Akt pathway activation. Conclusion: Lithospermum erythrorhizon oil exerts multi-target, multi-pathway therapeutic effects in AD, potentially through suppressing Th2-mediated immune responses and the PI3K-Akt signaling pathway, suggesting novel avenues for AD treatment strategies.http://www.sciencedirect.com/science/article/pii/S2405844025000878Atopic dermatitisLithospermum erythrorhizon oilNetwork pharmacologyExperimental validationMolecular mechanismPI3K-Akt signaling pathway |
| spellingShingle | Weisheng Hu Yinlan Wang Yingjie Zhou Junbao Shi Zengyan Li Xiaoling Jiang Qinyuan Wu Changming Zhong Huilan Weng Sijie Ouyang Yuan Jing Xianxiang Cai Mingda Ye Ning Huang Exploration of the mechanism of Lithospermum erythrorhizon oil in treating atopic dermatitis based on network pharmacology and experimental validation of the PI3K-Akt pathway regulation Heliyon Atopic dermatitis Lithospermum erythrorhizon oil Network pharmacology Experimental validation Molecular mechanism PI3K-Akt signaling pathway |
| title | Exploration of the mechanism of Lithospermum erythrorhizon oil in treating atopic dermatitis based on network pharmacology and experimental validation of the PI3K-Akt pathway regulation |
| title_full | Exploration of the mechanism of Lithospermum erythrorhizon oil in treating atopic dermatitis based on network pharmacology and experimental validation of the PI3K-Akt pathway regulation |
| title_fullStr | Exploration of the mechanism of Lithospermum erythrorhizon oil in treating atopic dermatitis based on network pharmacology and experimental validation of the PI3K-Akt pathway regulation |
| title_full_unstemmed | Exploration of the mechanism of Lithospermum erythrorhizon oil in treating atopic dermatitis based on network pharmacology and experimental validation of the PI3K-Akt pathway regulation |
| title_short | Exploration of the mechanism of Lithospermum erythrorhizon oil in treating atopic dermatitis based on network pharmacology and experimental validation of the PI3K-Akt pathway regulation |
| title_sort | exploration of the mechanism of lithospermum erythrorhizon oil in treating atopic dermatitis based on network pharmacology and experimental validation of the pi3k akt pathway regulation |
| topic | Atopic dermatitis Lithospermum erythrorhizon oil Network pharmacology Experimental validation Molecular mechanism PI3K-Akt signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2405844025000878 |
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