Cargando…

Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression

Ulcerative colitis (UC) is associated with intestinal immune imbalance and inflammatory response. Because dehydrolovastatin (DLVT), a derivative of lovastatin, has been recently shown to inhibit inflammation and relieve immune arthritis induced by chemical stimuli, we studied its effect and possible...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Xu, Deng, Qing-Hua, Deng, Jian-Hua, Wang, Sheng-Ju, Chen, Qiu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Physiological Society and The Korean Society of Pharmacology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043998/
https://www.ncbi.nlm.nih.gov/pubmed/32140037
http://dx.doi.org/10.4196/kjpp.2020.24.2.137
_version_ 1783501488033628160
author Zhang, Xu
Deng, Qing-Hua
Deng, Jian-Hua
Wang, Sheng-Ju
Chen, Qiu
author_facet Zhang, Xu
Deng, Qing-Hua
Deng, Jian-Hua
Wang, Sheng-Ju
Chen, Qiu
author_sort Zhang, Xu
collection PubMed
description Ulcerative colitis (UC) is associated with intestinal immune imbalance and inflammatory response. Because dehydrolovastatin (DLVT), a derivative of lovastatin, has been recently shown to inhibit inflammation and relieve immune arthritis induced by chemical stimuli, we studied its effect and possible mechanism on UC induced by dextran sulfate sodium. The BALB/c mice were classified into six groups: normal control group, model group, DLVT high dose group, DLVT low dose group, salazosulfapyridine (SASP) group and lovastatin (LVT) group. The disease activity indices of UC and pathological changes were investigated. The myeloperoxidase (MPO) activity in colon tissue and inflammatory factors such as IL-6, IL-10, IL-17, and TNF-α in the serum were analyzed by ELISA, while the expression of NF-κB p65 protein in colon tissue was detected by immunohistochemistry and western blot. DLVT relieved the disease activity indices and pathological damage of the UC mice. Furthermore, DLVT significantly decreased MPO activity and improved the imbalance of inflammatory cytokines through inhibiting the expression of NF-κB p65. Meanwhile, the positive drug of SASP has a similar effect to DLVT, but the effect of DLVT in both decreasing IL-17, TNF-α, and increasing IL-10 was significantly stronger than that of SASP. These results suggest that DLVT may ameliorates the symptoms of UC.
format Online
Article
Text
id pubmed-7043998
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher The Korean Physiological Society and The Korean Society of Pharmacology
record_format MEDLINE/PubMed
spelling pubmed-70439982020-03-06 Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression Zhang, Xu Deng, Qing-Hua Deng, Jian-Hua Wang, Sheng-Ju Chen, Qiu Korean J Physiol Pharmacol Original Article Ulcerative colitis (UC) is associated with intestinal immune imbalance and inflammatory response. Because dehydrolovastatin (DLVT), a derivative of lovastatin, has been recently shown to inhibit inflammation and relieve immune arthritis induced by chemical stimuli, we studied its effect and possible mechanism on UC induced by dextran sulfate sodium. The BALB/c mice were classified into six groups: normal control group, model group, DLVT high dose group, DLVT low dose group, salazosulfapyridine (SASP) group and lovastatin (LVT) group. The disease activity indices of UC and pathological changes were investigated. The myeloperoxidase (MPO) activity in colon tissue and inflammatory factors such as IL-6, IL-10, IL-17, and TNF-α in the serum were analyzed by ELISA, while the expression of NF-κB p65 protein in colon tissue was detected by immunohistochemistry and western blot. DLVT relieved the disease activity indices and pathological damage of the UC mice. Furthermore, DLVT significantly decreased MPO activity and improved the imbalance of inflammatory cytokines through inhibiting the expression of NF-κB p65. Meanwhile, the positive drug of SASP has a similar effect to DLVT, but the effect of DLVT in both decreasing IL-17, TNF-α, and increasing IL-10 was significantly stronger than that of SASP. These results suggest that DLVT may ameliorates the symptoms of UC. The Korean Physiological Society and The Korean Society of Pharmacology 2020-03 2020-02-20 /pmc/articles/PMC7043998/ /pubmed/32140037 http://dx.doi.org/10.4196/kjpp.2020.24.2.137 Text en Copyright © Korean J Physiol Pharmacol http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Zhang, Xu
Deng, Qing-Hua
Deng, Jian-Hua
Wang, Sheng-Ju
Chen, Qiu
Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression
title Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression
title_full Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression
title_fullStr Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression
title_full_unstemmed Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression
title_short Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression
title_sort lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing nf-κb and inflammatory cytokine expression
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043998/
https://www.ncbi.nlm.nih.gov/pubmed/32140037
http://dx.doi.org/10.4196/kjpp.2020.24.2.137
work_keys_str_mv AT zhangxu lovastatinderivativedehydrolovastatinamelioratesulcerativecolitisinmicebysuppressingnfkbandinflammatorycytokineexpression
AT dengqinghua lovastatinderivativedehydrolovastatinamelioratesulcerativecolitisinmicebysuppressingnfkbandinflammatorycytokineexpression
AT dengjianhua lovastatinderivativedehydrolovastatinamelioratesulcerativecolitisinmicebysuppressingnfkbandinflammatorycytokineexpression
AT wangshengju lovastatinderivativedehydrolovastatinamelioratesulcerativecolitisinmicebysuppressingnfkbandinflammatorycytokineexpression
AT chenqiu lovastatinderivativedehydrolovastatinamelioratesulcerativecolitisinmicebysuppressingnfkbandinflammatorycytokineexpression