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Total Flavonoids of Glycyrrhiza uralensis Alleviates Irinotecan-Induced Colitis via Modification of Gut Microbiota and Fecal Metabolism

Irinotecan (CPT-11)-induced gastrointestinal toxicity strongly limits its anticancer efficacy. Glycyrrhiza uralensis Fisch., especially flavonoids, has strong anti-inflammatory and immunomodulatory activities. Herein, we investigate the protective effect of the total flavonoids of G. uralensis (TFGU...

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Autores principales: Yue, Shi-Jun, Qin, Yi-Feng, Kang, An, Tao, Hui-Juan, Zhou, Gui-Sheng, Chen, Yan-Yan, Jiang, Jian-Qin, Tang, Yu-Ping, Duan, Jin-Ao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138048/
https://www.ncbi.nlm.nih.gov/pubmed/34025639
http://dx.doi.org/10.3389/fimmu.2021.628358
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author Yue, Shi-Jun
Qin, Yi-Feng
Kang, An
Tao, Hui-Juan
Zhou, Gui-Sheng
Chen, Yan-Yan
Jiang, Jian-Qin
Tang, Yu-Ping
Duan, Jin-Ao
author_facet Yue, Shi-Jun
Qin, Yi-Feng
Kang, An
Tao, Hui-Juan
Zhou, Gui-Sheng
Chen, Yan-Yan
Jiang, Jian-Qin
Tang, Yu-Ping
Duan, Jin-Ao
author_sort Yue, Shi-Jun
collection PubMed
description Irinotecan (CPT-11)-induced gastrointestinal toxicity strongly limits its anticancer efficacy. Glycyrrhiza uralensis Fisch., especially flavonoids, has strong anti-inflammatory and immunomodulatory activities. Herein, we investigate the protective effect of the total flavonoids of G. uralensis (TFGU) on CPT-11–induced colitis mice from the perspective of gut microbiota and fecal metabolism. The body weight and colon length of mice were measured. Our results showed that oral administration of TFGU significantly attenuated the loss of body weight and the shortening of colon length induced by CPT-11. The elevated disease activity index and histological score of colon as well as the up-regulated mRNA and protein levels of TNF-α, IL-1β, and IL-6 in the colonic tissue of CPT-11–treated mice were significantly decreased by TFGU. Meanwhile, TFGU restored the perturbed gut microbial structure and function in CPT-11–treated mice to near normal level. TFGU also effectively reversed the CPT-11–induced fecal metabolic disorders in mice, mainly call backing the hypoxanthine and uric acid in purine metabolism. Spearman’s correlation analysis further revealed that Lactobacillus abundance negatively correlated with fecal uric acid concentration, suggesting the pivotal role of gut microbiota in CPT-11–induced colitis. Since uric acid is a ligand of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, TFGU was further validated to inhibit the activation of NLRP3 inflammasome by CPT-11. Our findings suggest TFGU can correct the overall gut microbial dysbiosis and fecal metabolic disorders in the CPT-11–induced colitis mice, underscoring the potential of using dietary G. uralensis as a chemotherapeutic adjuvant.
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spelling pubmed-81380482021-05-22 Total Flavonoids of Glycyrrhiza uralensis Alleviates Irinotecan-Induced Colitis via Modification of Gut Microbiota and Fecal Metabolism Yue, Shi-Jun Qin, Yi-Feng Kang, An Tao, Hui-Juan Zhou, Gui-Sheng Chen, Yan-Yan Jiang, Jian-Qin Tang, Yu-Ping Duan, Jin-Ao Front Immunol Immunology Irinotecan (CPT-11)-induced gastrointestinal toxicity strongly limits its anticancer efficacy. Glycyrrhiza uralensis Fisch., especially flavonoids, has strong anti-inflammatory and immunomodulatory activities. Herein, we investigate the protective effect of the total flavonoids of G. uralensis (TFGU) on CPT-11–induced colitis mice from the perspective of gut microbiota and fecal metabolism. The body weight and colon length of mice were measured. Our results showed that oral administration of TFGU significantly attenuated the loss of body weight and the shortening of colon length induced by CPT-11. The elevated disease activity index and histological score of colon as well as the up-regulated mRNA and protein levels of TNF-α, IL-1β, and IL-6 in the colonic tissue of CPT-11–treated mice were significantly decreased by TFGU. Meanwhile, TFGU restored the perturbed gut microbial structure and function in CPT-11–treated mice to near normal level. TFGU also effectively reversed the CPT-11–induced fecal metabolic disorders in mice, mainly call backing the hypoxanthine and uric acid in purine metabolism. Spearman’s correlation analysis further revealed that Lactobacillus abundance negatively correlated with fecal uric acid concentration, suggesting the pivotal role of gut microbiota in CPT-11–induced colitis. Since uric acid is a ligand of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, TFGU was further validated to inhibit the activation of NLRP3 inflammasome by CPT-11. Our findings suggest TFGU can correct the overall gut microbial dysbiosis and fecal metabolic disorders in the CPT-11–induced colitis mice, underscoring the potential of using dietary G. uralensis as a chemotherapeutic adjuvant. Frontiers Media S.A. 2021-05-07 /pmc/articles/PMC8138048/ /pubmed/34025639 http://dx.doi.org/10.3389/fimmu.2021.628358 Text en Copyright © 2021 Yue, Qin, Kang, Tao, Zhou, Chen, Jiang, Tang and Duan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Yue, Shi-Jun
Qin, Yi-Feng
Kang, An
Tao, Hui-Juan
Zhou, Gui-Sheng
Chen, Yan-Yan
Jiang, Jian-Qin
Tang, Yu-Ping
Duan, Jin-Ao
Total Flavonoids of Glycyrrhiza uralensis Alleviates Irinotecan-Induced Colitis via Modification of Gut Microbiota and Fecal Metabolism
title Total Flavonoids of Glycyrrhiza uralensis Alleviates Irinotecan-Induced Colitis via Modification of Gut Microbiota and Fecal Metabolism
title_full Total Flavonoids of Glycyrrhiza uralensis Alleviates Irinotecan-Induced Colitis via Modification of Gut Microbiota and Fecal Metabolism
title_fullStr Total Flavonoids of Glycyrrhiza uralensis Alleviates Irinotecan-Induced Colitis via Modification of Gut Microbiota and Fecal Metabolism
title_full_unstemmed Total Flavonoids of Glycyrrhiza uralensis Alleviates Irinotecan-Induced Colitis via Modification of Gut Microbiota and Fecal Metabolism
title_short Total Flavonoids of Glycyrrhiza uralensis Alleviates Irinotecan-Induced Colitis via Modification of Gut Microbiota and Fecal Metabolism
title_sort total flavonoids of glycyrrhiza uralensis alleviates irinotecan-induced colitis via modification of gut microbiota and fecal metabolism
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138048/
https://www.ncbi.nlm.nih.gov/pubmed/34025639
http://dx.doi.org/10.3389/fimmu.2021.628358
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