Network pharmacology and in vivo and in vitro experiments to determine the mechanism behind the effects of Jiawei Yanghe decoction via TLR4/Myd88/NF-κB against mastitis

Background: In the Qing dynasty, Yanghe decoction was as a therapeutic soup for effectively treating chronic inflammatory disorders. It was used as a therapeutic soup for effectively treating chronic inflammatory disorders. In the clinical use of Yanghe decoction, the adjustment of the medication fo...

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Main Authors: Jing Zhao, Liuyan Xu, Lingyan Lv, Liuyi Wang, Xuan Wang, Chen Liang, Chunhui Wang, Yan Qiu, Xiaohua Pei
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S240584402308427X
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author Jing Zhao
Liuyan Xu
Lingyan Lv
Liuyi Wang
Xuan Wang
Chen Liang
Chunhui Wang
Yan Qiu
Xiaohua Pei
author_facet Jing Zhao
Liuyan Xu
Lingyan Lv
Liuyi Wang
Xuan Wang
Chen Liang
Chunhui Wang
Yan Qiu
Xiaohua Pei
author_sort Jing Zhao
collection DOAJ
description Background: In the Qing dynasty, Yanghe decoction was as a therapeutic soup for effectively treating chronic inflammatory disorders. It was used as a therapeutic soup for effectively treating chronic inflammatory disorders. In the clinical use of Yanghe decoction, the adjustment of the medication for a variety of inflammatory diseases have therapeutic effect, including mastitis. Therefore, Jiawei Yanghe decoction (JWYHD) may be used to treat inflammatory breast diseases. Methods: First, LM- and JWYHD-related components were retrieved from the database and analysis platform. Next, protein–protein interaction networks were constructed to screen the key targets, and gene ontology and Kyoto encyclopedia of gene and genome enrichment analyses were performed to predict the potential biological functions and mechanisms of JWYHD. Simultaneously, the JWYHD samples were collected and analyzed by UPLC–HRMS. Finally, in vivo and in vitro experiments were conducted to construct animal and cellular inflammation models of mastitis with LPS. Pathological changes in the mammary tissues were detected. Enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and Western blotting was performed to determine the mRNA and protein levels of inflammatory cytokines and toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B signaling pathway in the breast tissues to elucidate the potential underlying mechanisms of anti-mastitis effects of JWYHD from different aspects. Results: In total, 103 compounds were detected in JWYHD by UPLC–HRMS. 691 active ingredients of JWYHD were screened by network pharmacology, and 47 LM-related targets were identified. The PPI network analysis of the targets revealed the 5 core targets. The KEGG enrichment results established the NF-κB signaling pathways as the core. After JWYHD intervention, low inflammatory enrichment and mild inflammatory damage in breast tissues were observed. Furthermore, JWYHD treatment affected mammary gland inflammatory cytokines and the TLR4/Myd88/NF-κB signaling pathway by considerably reducing the respective protein levels and gene expression; thus, JWYHD alleviated LM symptoms. Conclusions: We hypothesized and demonstrated the anti-inflammatory effects of JWYHD by cytokine regulation via the TLR4/Myd88/NF-κB signaling pathway. In conclusion, JWYHD showed its potential in LM treatment and in treating other acute and chronic inflammatory diseases.
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spelling doaj.art-c36480dc03624be6b26f839d2a5f44cb2023-12-02T07:01:31ZengElsevierHeliyon2405-84402023-11-01911e21219Network pharmacology and in vivo and in vitro experiments to determine the mechanism behind the effects of Jiawei Yanghe decoction via TLR4/Myd88/NF-κB against mastitisJing Zhao0Liuyan Xu1Lingyan Lv2Liuyi Wang3Xuan Wang4Chen Liang5Chunhui Wang6Yan Qiu7Xiaohua Pei8Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, 100029, ChinaBeijing University of Chinese Medicine Third Affiliated Hospital, Beijing, 100029, ChinaBeijing University of Chinese Medicine Third Affiliated Hospital, Beijing, 100029, ChinaXiamen University, Xiamen, 361102, ChinaBeijing University of Chinese Medicine Third Affiliated Hospital, Beijing, 100029, ChinaDongfang Hospital Beijing University of Chinese Medicine, Beijing, 100078, ChinaFangshan Hospital Beijing University of Chinese Medicine, Beijing, 102488, ChinaEye Institute of Xiamen University, Xiamen, 361102, China; Corresponding author.Xiamen Hospital of Beijing University of Traditional Chinese Medicine, Xiamen, 361015, China; Corresponding author.Background: In the Qing dynasty, Yanghe decoction was as a therapeutic soup for effectively treating chronic inflammatory disorders. It was used as a therapeutic soup for effectively treating chronic inflammatory disorders. In the clinical use of Yanghe decoction, the adjustment of the medication for a variety of inflammatory diseases have therapeutic effect, including mastitis. Therefore, Jiawei Yanghe decoction (JWYHD) may be used to treat inflammatory breast diseases. Methods: First, LM- and JWYHD-related components were retrieved from the database and analysis platform. Next, protein–protein interaction networks were constructed to screen the key targets, and gene ontology and Kyoto encyclopedia of gene and genome enrichment analyses were performed to predict the potential biological functions and mechanisms of JWYHD. Simultaneously, the JWYHD samples were collected and analyzed by UPLC–HRMS. Finally, in vivo and in vitro experiments were conducted to construct animal and cellular inflammation models of mastitis with LPS. Pathological changes in the mammary tissues were detected. Enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and Western blotting was performed to determine the mRNA and protein levels of inflammatory cytokines and toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B signaling pathway in the breast tissues to elucidate the potential underlying mechanisms of anti-mastitis effects of JWYHD from different aspects. Results: In total, 103 compounds were detected in JWYHD by UPLC–HRMS. 691 active ingredients of JWYHD were screened by network pharmacology, and 47 LM-related targets were identified. The PPI network analysis of the targets revealed the 5 core targets. The KEGG enrichment results established the NF-κB signaling pathways as the core. After JWYHD intervention, low inflammatory enrichment and mild inflammatory damage in breast tissues were observed. Furthermore, JWYHD treatment affected mammary gland inflammatory cytokines and the TLR4/Myd88/NF-κB signaling pathway by considerably reducing the respective protein levels and gene expression; thus, JWYHD alleviated LM symptoms. Conclusions: We hypothesized and demonstrated the anti-inflammatory effects of JWYHD by cytokine regulation via the TLR4/Myd88/NF-κB signaling pathway. In conclusion, JWYHD showed its potential in LM treatment and in treating other acute and chronic inflammatory diseases.http://www.sciencedirect.com/science/article/pii/S240584402308427XLactation mastitisJiawei Yanghe decoctionNetwork pharmacologyMolecular dockingLPSTLR4/Myd88/NF-κB
spellingShingle Jing Zhao
Liuyan Xu
Lingyan Lv
Liuyi Wang
Xuan Wang
Chen Liang
Chunhui Wang
Yan Qiu
Xiaohua Pei
Network pharmacology and in vivo and in vitro experiments to determine the mechanism behind the effects of Jiawei Yanghe decoction via TLR4/Myd88/NF-κB against mastitis
Heliyon
Lactation mastitis
Jiawei Yanghe decoction
Network pharmacology
Molecular docking
LPS
TLR4/Myd88/NF-κB
title Network pharmacology and in vivo and in vitro experiments to determine the mechanism behind the effects of Jiawei Yanghe decoction via TLR4/Myd88/NF-κB against mastitis
title_full Network pharmacology and in vivo and in vitro experiments to determine the mechanism behind the effects of Jiawei Yanghe decoction via TLR4/Myd88/NF-κB against mastitis
title_fullStr Network pharmacology and in vivo and in vitro experiments to determine the mechanism behind the effects of Jiawei Yanghe decoction via TLR4/Myd88/NF-κB against mastitis
title_full_unstemmed Network pharmacology and in vivo and in vitro experiments to determine the mechanism behind the effects of Jiawei Yanghe decoction via TLR4/Myd88/NF-κB against mastitis
title_short Network pharmacology and in vivo and in vitro experiments to determine the mechanism behind the effects of Jiawei Yanghe decoction via TLR4/Myd88/NF-κB against mastitis
title_sort network pharmacology and in vivo and in vitro experiments to determine the mechanism behind the effects of jiawei yanghe decoction via tlr4 myd88 nf κb against mastitis
topic Lactation mastitis
Jiawei Yanghe decoction
Network pharmacology
Molecular docking
LPS
TLR4/Myd88/NF-κB
url http://www.sciencedirect.com/science/article/pii/S240584402308427X
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