Kaempferol relieves the DSS-induced chronic colitis in C57BL/6J mice, alleviates intestinal angiogenesis, and regulates colonic microflora structure

Purpose: The progression of chronic colitis is accompanied by an increase in inflammation and intestinal angiogenesis. Kaempferol, a dietary flavonoid, has been shown to exhibit anti-inflammatory and anti-angiogenic properties. However, the anti-angiogenic effect of kaempferol in chronic colitis has...

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Main Authors: Ruyang Yu, Qilyu Zhou, Tianlong Liu, Ping Liu, Hong Li, Yifei Bian, Zhongjie Liu
Format: Article
Language:English
Published: Elsevier 2023-08-01
Series:Journal of Functional Foods
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1756464623002463
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author Ruyang Yu
Qilyu Zhou
Tianlong Liu
Ping Liu
Hong Li
Yifei Bian
Zhongjie Liu
author_facet Ruyang Yu
Qilyu Zhou
Tianlong Liu
Ping Liu
Hong Li
Yifei Bian
Zhongjie Liu
author_sort Ruyang Yu
collection DOAJ
description Purpose: The progression of chronic colitis is accompanied by an increase in inflammation and intestinal angiogenesis. Kaempferol, a dietary flavonoid, has been shown to exhibit anti-inflammatory and anti-angiogenic properties. However, the anti-angiogenic effect of kaempferol in chronic colitis has not been elucidated. The present study aimed to investigate the effects of kaempferol on intestinal angiogenesis and microflora of mice with chronic colitis. Methods: The dextran sulfate sodium (DSS)-induced chronic colitis mouse model was used in this study. The effects of kaempferol and 5-aminosalicylic acid (5-ASA) were evaluated by histopathology, ELISA, western blot, and immunohistochemistry. The integrity of the gut-vascular barrier (GVB) was studied using FITC-dextran and D-Lactate. The colonic flora of mice was analyzed using 16S rDNA sequencing. Results: Kaempferol supplementation could relieve the symptoms (weight loss, colonic pathological injury, hemogram index, etc.) of chronic colitis in mice, down-regulate the secretion of inflammatory factors (IL-1β, IL-6, TNF-α, and CRP), and modulate the expression of inflammatory regulatory proteins (COX-2, TRAF6, and IL-22BP) in colonic tissues. Moreover, kaempferol decreased the secretion of colonic VEGF and NO, high intestinal microvascular density (MVD), and abnormal expression of VEGFR2 caused by DSS. Our finding also indicated that kaempferol alleviates chronic colitis by maintaining GVB, suppressing pro-inflammatory flora (Verrucomicrobiota, Campilobacterota, and Desulfobacterota), and enhancing the abundance of beneficial flora (Actinobacteria, and Odoribacter). Conclusion: Kaempferol exerted its therapeutic effect on chronic colitis by alleviating the inflammation of the colon and intestinal angiogenesis, maintaining the integrity of GVB, and regulating colonic microflora. Our study demonstrated similar pharmacological effects of kaempferol to 5-ASA (drug of clinical application for intestinal inflammatory diseases), and revealed the potential of kaempferol treatment as a preventive strategy for chronic colitis.
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spelling doaj.art-5ed13f7c17754eea87cb8b5ffc9acf832023-08-09T04:32:26ZengElsevierJournal of Functional Foods1756-46462023-08-01107105646Kaempferol relieves the DSS-induced chronic colitis in C57BL/6J mice, alleviates intestinal angiogenesis, and regulates colonic microflora structureRuyang Yu0Qilyu Zhou1Tianlong Liu2Ping Liu3Hong Li4Yifei Bian5Zhongjie Liu6Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Ji’nan 250300, PR China; College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR ChinaCollege of Veterinary Medicine, China Agricultural University, Beijing 100193, PR ChinaCollege of Veterinary Medicine, China Agricultural University, Beijing 100193, PR ChinaCollege of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Lin’an 311300, PR ChinaBeijing Center for Disease Control and Prevention, Beijing 100013, PR ChinaInnovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Ji’nan 250300, PR China; Corresponding authors.College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China; Corresponding authors.Purpose: The progression of chronic colitis is accompanied by an increase in inflammation and intestinal angiogenesis. Kaempferol, a dietary flavonoid, has been shown to exhibit anti-inflammatory and anti-angiogenic properties. However, the anti-angiogenic effect of kaempferol in chronic colitis has not been elucidated. The present study aimed to investigate the effects of kaempferol on intestinal angiogenesis and microflora of mice with chronic colitis. Methods: The dextran sulfate sodium (DSS)-induced chronic colitis mouse model was used in this study. The effects of kaempferol and 5-aminosalicylic acid (5-ASA) were evaluated by histopathology, ELISA, western blot, and immunohistochemistry. The integrity of the gut-vascular barrier (GVB) was studied using FITC-dextran and D-Lactate. The colonic flora of mice was analyzed using 16S rDNA sequencing. Results: Kaempferol supplementation could relieve the symptoms (weight loss, colonic pathological injury, hemogram index, etc.) of chronic colitis in mice, down-regulate the secretion of inflammatory factors (IL-1β, IL-6, TNF-α, and CRP), and modulate the expression of inflammatory regulatory proteins (COX-2, TRAF6, and IL-22BP) in colonic tissues. Moreover, kaempferol decreased the secretion of colonic VEGF and NO, high intestinal microvascular density (MVD), and abnormal expression of VEGFR2 caused by DSS. Our finding also indicated that kaempferol alleviates chronic colitis by maintaining GVB, suppressing pro-inflammatory flora (Verrucomicrobiota, Campilobacterota, and Desulfobacterota), and enhancing the abundance of beneficial flora (Actinobacteria, and Odoribacter). Conclusion: Kaempferol exerted its therapeutic effect on chronic colitis by alleviating the inflammation of the colon and intestinal angiogenesis, maintaining the integrity of GVB, and regulating colonic microflora. Our study demonstrated similar pharmacological effects of kaempferol to 5-ASA (drug of clinical application for intestinal inflammatory diseases), and revealed the potential of kaempferol treatment as a preventive strategy for chronic colitis.http://www.sciencedirect.com/science/article/pii/S1756464623002463Chronic colitisIntestinal angiogenesisKaempferolGVBColonic microflora
spellingShingle Ruyang Yu
Qilyu Zhou
Tianlong Liu
Ping Liu
Hong Li
Yifei Bian
Zhongjie Liu
Kaempferol relieves the DSS-induced chronic colitis in C57BL/6J mice, alleviates intestinal angiogenesis, and regulates colonic microflora structure
Journal of Functional Foods
Chronic colitis
Intestinal angiogenesis
Kaempferol
GVB
Colonic microflora
title Kaempferol relieves the DSS-induced chronic colitis in C57BL/6J mice, alleviates intestinal angiogenesis, and regulates colonic microflora structure
title_full Kaempferol relieves the DSS-induced chronic colitis in C57BL/6J mice, alleviates intestinal angiogenesis, and regulates colonic microflora structure
title_fullStr Kaempferol relieves the DSS-induced chronic colitis in C57BL/6J mice, alleviates intestinal angiogenesis, and regulates colonic microflora structure
title_full_unstemmed Kaempferol relieves the DSS-induced chronic colitis in C57BL/6J mice, alleviates intestinal angiogenesis, and regulates colonic microflora structure
title_short Kaempferol relieves the DSS-induced chronic colitis in C57BL/6J mice, alleviates intestinal angiogenesis, and regulates colonic microflora structure
title_sort kaempferol relieves the dss induced chronic colitis in c57bl 6j mice alleviates intestinal angiogenesis and regulates colonic microflora structure
topic Chronic colitis
Intestinal angiogenesis
Kaempferol
GVB
Colonic microflora
url http://www.sciencedirect.com/science/article/pii/S1756464623002463
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