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Protective Effects of Oxyberberine in 5-Fluorouracil-Induced Intestinal Mucositis in the Mice Model

Berberine (BBR), a major active constituent of Rhizoma coptidis, was reported to exert beneficial effects on intestinal mucositis (IM) induced by 5-fluorouracil (5-FU). However, the bioavailability of BBR is extremely low, and its metabolites were perceived to contribute to its prominent pharmacolog...

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Autores principales: Huang, Ronglei, Ai, Gaoxiang, Zhong, Linjiang, Mai, Liting, Chen, Jian-Nan, Liu, Yuhong, Li, Yucui, Huang, Xiaoqi, Su, Ziren, Zhan, Janis Ya-Xian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170416/
https://www.ncbi.nlm.nih.gov/pubmed/35677366
http://dx.doi.org/10.1155/2022/1238358
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author Huang, Ronglei
Ai, Gaoxiang
Zhong, Linjiang
Mai, Liting
Chen, Jian-Nan
Liu, Yuhong
Li, Yucui
Huang, Xiaoqi
Su, Ziren
Zhan, Janis Ya-Xian
author_facet Huang, Ronglei
Ai, Gaoxiang
Zhong, Linjiang
Mai, Liting
Chen, Jian-Nan
Liu, Yuhong
Li, Yucui
Huang, Xiaoqi
Su, Ziren
Zhan, Janis Ya-Xian
author_sort Huang, Ronglei
collection PubMed
description Berberine (BBR), a major active constituent of Rhizoma coptidis, was reported to exert beneficial effects on intestinal mucositis (IM) induced by 5-fluorouracil (5-FU). However, the bioavailability of BBR is extremely low, and its metabolites were perceived to contribute to its prominent pharmacological activities. Oxyberberine (OBB) is a gut metabolite of BBR, which has been reported to have a superior anti-inflammatory effect in experimental colitis. However, its anti-inflammatory effects against 5-FU-induced IM mice have not yet been investigated. Hence, the purpose of this study was to reveal the protective effects of OBB on IM induced by 5-FU and investigate its potential underlying mechanism. The IM mice model was induced by receiving 5-FU (60 mg/kg, i.p.) for five days. Meanwhile, BBR (50 mg/kg) and OBB (12.5, 25, and 50 mg/kg) were given prior to 30 min intraperitoneal injection of 5-FU for seven days. Results indicated that OBB ameliorated body weight loss, anorexia, diarrhea, and histopathological damage in 5-FU-induced IM mice. After OBB administration, the amounts of MDA, SOD, and GSH altered by IM were remarkably restored. OBB was also observed to dramatically decrease the levels of TNF-α, IL-8, IL-6, COX-2, and iNOS and promote the release of IL-10. Besides, OBB distinctly upregulated the mRNA expressions of PCNA, ZO-1, occludin, and mucin-1, which could improve intestinal homeostasis in IM mice. OBB also blocked the activation of the upstream TLR4/MyD88 signaling pathway, and then it inhibited the phosphorylation of the NF-κB and MAPK pathways. Importantly, compared with BBR, OBB displayed a superior therapeutic effect to BBR in alleviating 5-FU-induced IM mice. These results indicated that OBB has considerable potential to become a novel candidate drug against IM.
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spelling pubmed-91704162022-06-07 Protective Effects of Oxyberberine in 5-Fluorouracil-Induced Intestinal Mucositis in the Mice Model Huang, Ronglei Ai, Gaoxiang Zhong, Linjiang Mai, Liting Chen, Jian-Nan Liu, Yuhong Li, Yucui Huang, Xiaoqi Su, Ziren Zhan, Janis Ya-Xian Evid Based Complement Alternat Med Research Article Berberine (BBR), a major active constituent of Rhizoma coptidis, was reported to exert beneficial effects on intestinal mucositis (IM) induced by 5-fluorouracil (5-FU). However, the bioavailability of BBR is extremely low, and its metabolites were perceived to contribute to its prominent pharmacological activities. Oxyberberine (OBB) is a gut metabolite of BBR, which has been reported to have a superior anti-inflammatory effect in experimental colitis. However, its anti-inflammatory effects against 5-FU-induced IM mice have not yet been investigated. Hence, the purpose of this study was to reveal the protective effects of OBB on IM induced by 5-FU and investigate its potential underlying mechanism. The IM mice model was induced by receiving 5-FU (60 mg/kg, i.p.) for five days. Meanwhile, BBR (50 mg/kg) and OBB (12.5, 25, and 50 mg/kg) were given prior to 30 min intraperitoneal injection of 5-FU for seven days. Results indicated that OBB ameliorated body weight loss, anorexia, diarrhea, and histopathological damage in 5-FU-induced IM mice. After OBB administration, the amounts of MDA, SOD, and GSH altered by IM were remarkably restored. OBB was also observed to dramatically decrease the levels of TNF-α, IL-8, IL-6, COX-2, and iNOS and promote the release of IL-10. Besides, OBB distinctly upregulated the mRNA expressions of PCNA, ZO-1, occludin, and mucin-1, which could improve intestinal homeostasis in IM mice. OBB also blocked the activation of the upstream TLR4/MyD88 signaling pathway, and then it inhibited the phosphorylation of the NF-κB and MAPK pathways. Importantly, compared with BBR, OBB displayed a superior therapeutic effect to BBR in alleviating 5-FU-induced IM mice. These results indicated that OBB has considerable potential to become a novel candidate drug against IM. Hindawi 2022-05-30 /pmc/articles/PMC9170416/ /pubmed/35677366 http://dx.doi.org/10.1155/2022/1238358 Text en Copyright © 2022 Ronglei Huang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Huang, Ronglei
Ai, Gaoxiang
Zhong, Linjiang
Mai, Liting
Chen, Jian-Nan
Liu, Yuhong
Li, Yucui
Huang, Xiaoqi
Su, Ziren
Zhan, Janis Ya-Xian
Protective Effects of Oxyberberine in 5-Fluorouracil-Induced Intestinal Mucositis in the Mice Model
title Protective Effects of Oxyberberine in 5-Fluorouracil-Induced Intestinal Mucositis in the Mice Model
title_full Protective Effects of Oxyberberine in 5-Fluorouracil-Induced Intestinal Mucositis in the Mice Model
title_fullStr Protective Effects of Oxyberberine in 5-Fluorouracil-Induced Intestinal Mucositis in the Mice Model
title_full_unstemmed Protective Effects of Oxyberberine in 5-Fluorouracil-Induced Intestinal Mucositis in the Mice Model
title_short Protective Effects of Oxyberberine in 5-Fluorouracil-Induced Intestinal Mucositis in the Mice Model
title_sort protective effects of oxyberberine in 5-fluorouracil-induced intestinal mucositis in the mice model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170416/
https://www.ncbi.nlm.nih.gov/pubmed/35677366
http://dx.doi.org/10.1155/2022/1238358
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