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Original Article

Korean J Physiol Pharmacol 2020; 24(2): 137-147

Published online March 1, 2020 https://doi.org/10.4196/kjpp.2020.24.2.137

Copyright © The Korean Journal of Physiology & Pharmacology.

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

Xu Zhang1, Qing-Hua Deng2,*, Jian-Hua Deng3, Sheng-Ju Wang1, and Qiu Chen1,*

1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu City 610072, Sichuan Province, 2Chongqing Medical and Pharmaceutical College, Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing City 401331, 3People's Hospital of Shizhu County, Chongqing City 409100, P.R. China

Correspondence to:*Qing-Hua Deng
E-mail: dengqinghua2000@163.com
*Qiu Chen
E-mail: chenqiu1005@cdutcm.edu.cn

Received: June 4, 2019; Revised: July 25, 2019; Accepted: July 26, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.

Keywords: Dehydrolovastatin, Inflammation, NF-ΚB, Statins, Ulcerative colitis