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Tanshinone ⅡA participates in the treatment of endometriosis by regulating adhesion, invasion, angiogenesis and inhibition of PI3K/Akt/mTOR signaling pathway

Endometriosis (EMs) is a common gynecological disorder characterized by abnormal growth of the endometrial stroma and glands outside the uterus. Tanshinone IIA, the active component of Chinese medicine Danshen (Salvia miltiorrhiza Bge.), has a number of pharmacological effects such as anti-inflammat...

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Autores principales: Zhang, Xiaoxiao, Li, Shumiao, Chen, Zhenzhen, Liang, Wei, Pei, Shuting, Gou, Feiyue, Jia, Zhicheng, Geng, Zhaoyang, Gong, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568248/
https://www.ncbi.nlm.nih.gov/pubmed/37800602
http://dx.doi.org/10.3892/mmr.2023.13108
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author Zhang, Xiaoxiao
Li, Shumiao
Chen, Zhenzhen
Liang, Wei
Pei, Shuting
Gou, Feiyue
Jia, Zhicheng
Geng, Zhaoyang
Gong, Xin
author_facet Zhang, Xiaoxiao
Li, Shumiao
Chen, Zhenzhen
Liang, Wei
Pei, Shuting
Gou, Feiyue
Jia, Zhicheng
Geng, Zhaoyang
Gong, Xin
author_sort Zhang, Xiaoxiao
collection PubMed
description Endometriosis (EMs) is a common gynecological disorder characterized by abnormal growth of the endometrial stroma and glands outside the uterus. Tanshinone IIA, the active component of Chinese medicine Danshen (Salvia miltiorrhiza Bge.), has a number of pharmacological effects such as anti-inflammation and anti-oxidation and serves a significant role in the treatment of EMs. In the present study, network pharmacology and experimental validation were used to elucidate the potential mechanism of tanshinone IIA for treating EMs. Several databases were used to collect information on EMs and tanshinone IIA and cross-targets for tanshinone IIA and EMs finally obtained. A total of 64 common targets were found between tanshinone IIA and EMs. Subsequently, a protein-protein interaction network was constructed, a total of 14 core targets were screened for enrichment analysis. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. The network pharmacology showed that intercellular adhesion molecule (ICAM)-1, MMP-9 and VEGF are the core targets while PI3K/AKT pathway and mTOR pathway are the main signaling pathways through which tanshinone IIA regulates relevant biological processes to intervene in EMs. Finally, the therapeutic role and mechanism of tanshinone IIA on EMs was verified in vivo. Female Sprague-Dawley rats were treated by autologous transplantation to establish EMs. Serum inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The expression of ICAM-1, MMP-9 and VEGF in ectopic endometrial tissues of rats was determined by immunohistochemical. The expression of PI3K/Akt/mTOR pathway-related proteins and genes was detected by western blotting and quantitative PCR. It was found that tanshinone IIA treatment significantly decreased the formation of ectopic endometrium by reducing serum levels of TNF-α and IL-1β, and down regulating the levels of ICAM-1, MMP-9 and VEGF in ectopic uterine tissue. In addition, tanshinone IIA can also block the activation of PI3K/Akt/mTOR signaling pathway by reducing the expression of related proteins and genes. In conclusion, tanshinone IIA can regulate adhesion, invasion and angiogenesis, thereby improving the pathological morphology of ectopic endometrium and inhibiting the formation of ectopic lesions. The PI3K/Akt/mTOR signaling pathway may play a key role in controlling this process.
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spelling pubmed-105682482023-10-13 Tanshinone ⅡA participates in the treatment of endometriosis by regulating adhesion, invasion, angiogenesis and inhibition of PI3K/Akt/mTOR signaling pathway Zhang, Xiaoxiao Li, Shumiao Chen, Zhenzhen Liang, Wei Pei, Shuting Gou, Feiyue Jia, Zhicheng Geng, Zhaoyang Gong, Xin Mol Med Rep Articles Endometriosis (EMs) is a common gynecological disorder characterized by abnormal growth of the endometrial stroma and glands outside the uterus. Tanshinone IIA, the active component of Chinese medicine Danshen (Salvia miltiorrhiza Bge.), has a number of pharmacological effects such as anti-inflammation and anti-oxidation and serves a significant role in the treatment of EMs. In the present study, network pharmacology and experimental validation were used to elucidate the potential mechanism of tanshinone IIA for treating EMs. Several databases were used to collect information on EMs and tanshinone IIA and cross-targets for tanshinone IIA and EMs finally obtained. A total of 64 common targets were found between tanshinone IIA and EMs. Subsequently, a protein-protein interaction network was constructed, a total of 14 core targets were screened for enrichment analysis. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. The network pharmacology showed that intercellular adhesion molecule (ICAM)-1, MMP-9 and VEGF are the core targets while PI3K/AKT pathway and mTOR pathway are the main signaling pathways through which tanshinone IIA regulates relevant biological processes to intervene in EMs. Finally, the therapeutic role and mechanism of tanshinone IIA on EMs was verified in vivo. Female Sprague-Dawley rats were treated by autologous transplantation to establish EMs. Serum inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The expression of ICAM-1, MMP-9 and VEGF in ectopic endometrial tissues of rats was determined by immunohistochemical. The expression of PI3K/Akt/mTOR pathway-related proteins and genes was detected by western blotting and quantitative PCR. It was found that tanshinone IIA treatment significantly decreased the formation of ectopic endometrium by reducing serum levels of TNF-α and IL-1β, and down regulating the levels of ICAM-1, MMP-9 and VEGF in ectopic uterine tissue. In addition, tanshinone IIA can also block the activation of PI3K/Akt/mTOR signaling pathway by reducing the expression of related proteins and genes. In conclusion, tanshinone IIA can regulate adhesion, invasion and angiogenesis, thereby improving the pathological morphology of ectopic endometrium and inhibiting the formation of ectopic lesions. The PI3K/Akt/mTOR signaling pathway may play a key role in controlling this process. D.A. Spandidos 2023-09-29 /pmc/articles/PMC10568248/ /pubmed/37800602 http://dx.doi.org/10.3892/mmr.2023.13108 Text en Copyright: © Zhang et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhang, Xiaoxiao
Li, Shumiao
Chen, Zhenzhen
Liang, Wei
Pei, Shuting
Gou, Feiyue
Jia, Zhicheng
Geng, Zhaoyang
Gong, Xin
Tanshinone ⅡA participates in the treatment of endometriosis by regulating adhesion, invasion, angiogenesis and inhibition of PI3K/Akt/mTOR signaling pathway
title Tanshinone ⅡA participates in the treatment of endometriosis by regulating adhesion, invasion, angiogenesis and inhibition of PI3K/Akt/mTOR signaling pathway
title_full Tanshinone ⅡA participates in the treatment of endometriosis by regulating adhesion, invasion, angiogenesis and inhibition of PI3K/Akt/mTOR signaling pathway
title_fullStr Tanshinone ⅡA participates in the treatment of endometriosis by regulating adhesion, invasion, angiogenesis and inhibition of PI3K/Akt/mTOR signaling pathway
title_full_unstemmed Tanshinone ⅡA participates in the treatment of endometriosis by regulating adhesion, invasion, angiogenesis and inhibition of PI3K/Akt/mTOR signaling pathway
title_short Tanshinone ⅡA participates in the treatment of endometriosis by regulating adhesion, invasion, angiogenesis and inhibition of PI3K/Akt/mTOR signaling pathway
title_sort tanshinone ⅱa participates in the treatment of endometriosis by regulating adhesion, invasion, angiogenesis and inhibition of pi3k/akt/mtor signaling pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568248/
https://www.ncbi.nlm.nih.gov/pubmed/37800602
http://dx.doi.org/10.3892/mmr.2023.13108
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