Fisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis

Kangfeng Jiang,1,2,&ast; Jing Yang,3,&ast; Guanhong Xue,1,&ast; Ailing Dai,4 Haichong Wu1 1Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, People’s Republic of China; 2Department of Clinical Veterinary Medicine, College of V...

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Autores principales:	Jiang K, Yang J, Xue G, Dai A, Wu H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	fisetin endometritis inflammation oxidative stress tlr4/nrf2 Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/920137ee1d544f29932bc0bcf748def7
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spelling	oai:doaj.org-article:920137ee1d544f29932bc0bcf748def72021-12-02T14:35:44ZFisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis1178-7031https://doaj.org/article/920137ee1d544f29932bc0bcf748def72021-07-01T00:00:00Zhttps://www.dovepress.com/fisetin-ameliorates-the-inflammation-and-oxidative-stress-in-lipopolys-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Kangfeng Jiang,1,2,&ast; Jing Yang,3,&ast; Guanhong Xue,1,&ast; Ailing Dai,4 Haichong Wu1 1Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, People’s Republic of China; 2Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Yunnan Agricultural University, Kunming, Yunnan, 650201, People’s Republic of China; 3State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, People’s Republic of China; 4College of Life Sciences of Longyan University, Longyan, 364012, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haichong Wu Tel +86 571-88982091Email haichongwu@zju.edu.cnPurpose: Fisetin is a natural flavone of polyphenol, which widely exists in many fruits and vegetables and has many pharmacological activities. However, the mechanism involved remains largely unknown. Here, we investigate the mechanisms of fisetin on the inflammatory response and oxidative stress in LPS-induced endometritis model and bovine endometrial epithelial cell line (BEND).Methods: The function of fisetin was analyzed by network pharmacology. Effects of increasing doses of fisetin on inflammation and oxidative stress are studied in BALB/c mice with LPS-induced endometritis. The underlying mechanisms of antioxidant activity of fisetin were further explored in LPS-stimulated BEND cells.Results: The results showed that fisetin significantly alleviated LPS-induced inflammatory injury and oxidative stress both in vivo and in vitro. Further studies found that fisetin greatly inhibited the LPS stimulated TLR4 expression and nuclear translocation of nuclear factor-κB (NF-κB), thus reducing the pro-inflammatory mediators secretion. Silencing TLR4 reduced LPS-induced inflammatory responses. Moreover, we observed that fisetin evidently decreased ROS production but activated Nrf2/HO-1 pathway in LPS-stimulated BEND cells. To further explore the role of Nrf2 in fisetin-induced HO-1 protein expression, the specific siRNA was used to silence Nrf2 expression. Silencing Nrf2 abrogated the inhibitory effects of fisetin on LPS-induced pro-inflammatory cytokines TNF-α, IL-1β secretion, NADPH oxidase-4 (Nox4) and ROS production.Conclusion: In conclusion, fisetin effectively protected against LPS-induced oxidative stress and inflammatory responses which may be closely correlated to inhibition of TLR4-mediated ROS/NF-κB and activation of the Nrf2/HO-1 pathway.Keywords: fisetin, endometritis, inflammation, oxidative stress, TLR4/Nrf2Jiang KYang JXue GDai AWu HDove Medical Pressarticlefisetinendometritisinflammationoxidative stresstlr4/nrf2PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 2963-2978 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	fisetin endometritis inflammation oxidative stress tlr4/nrf2 Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	fisetin endometritis inflammation oxidative stress tlr4/nrf2 Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Jiang K Yang J Xue G Dai A Wu H Fisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis
description	Kangfeng Jiang,1,2,&ast; Jing Yang,3,&ast; Guanhong Xue,1,&ast; Ailing Dai,4 Haichong Wu1 1Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, People’s Republic of China; 2Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Yunnan Agricultural University, Kunming, Yunnan, 650201, People’s Republic of China; 3State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, People’s Republic of China; 4College of Life Sciences of Longyan University, Longyan, 364012, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haichong Wu Tel +86 571-88982091Email haichongwu@zju.edu.cnPurpose: Fisetin is a natural flavone of polyphenol, which widely exists in many fruits and vegetables and has many pharmacological activities. However, the mechanism involved remains largely unknown. Here, we investigate the mechanisms of fisetin on the inflammatory response and oxidative stress in LPS-induced endometritis model and bovine endometrial epithelial cell line (BEND).Methods: The function of fisetin was analyzed by network pharmacology. Effects of increasing doses of fisetin on inflammation and oxidative stress are studied in BALB/c mice with LPS-induced endometritis. The underlying mechanisms of antioxidant activity of fisetin were further explored in LPS-stimulated BEND cells.Results: The results showed that fisetin significantly alleviated LPS-induced inflammatory injury and oxidative stress both in vivo and in vitro. Further studies found that fisetin greatly inhibited the LPS stimulated TLR4 expression and nuclear translocation of nuclear factor-κB (NF-κB), thus reducing the pro-inflammatory mediators secretion. Silencing TLR4 reduced LPS-induced inflammatory responses. Moreover, we observed that fisetin evidently decreased ROS production but activated Nrf2/HO-1 pathway in LPS-stimulated BEND cells. To further explore the role of Nrf2 in fisetin-induced HO-1 protein expression, the specific siRNA was used to silence Nrf2 expression. Silencing Nrf2 abrogated the inhibitory effects of fisetin on LPS-induced pro-inflammatory cytokines TNF-α, IL-1β secretion, NADPH oxidase-4 (Nox4) and ROS production.Conclusion: In conclusion, fisetin effectively protected against LPS-induced oxidative stress and inflammatory responses which may be closely correlated to inhibition of TLR4-mediated ROS/NF-κB and activation of the Nrf2/HO-1 pathway.Keywords: fisetin, endometritis, inflammation, oxidative stress, TLR4/Nrf2
format	article
author	Jiang K Yang J Xue G Dai A Wu H
author_facet	Jiang K Yang J Xue G Dai A Wu H
author_sort	Jiang K
title	Fisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis
title_short	Fisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis
title_full	Fisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis
title_fullStr	Fisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis
title_full_unstemmed	Fisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis
title_sort	fisetin ameliorates the inflammation and oxidative stress in lipopolysaccharide-induced endometritis
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/920137ee1d544f29932bc0bcf748def7
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Fisetin Ameliorates the Inflammation and Oxidative Stress in Lipopolysaccharide-Induced Endometritis

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