Korean J Physiol Pharmacol.  2020 Mar;24(2):137-147. 10.4196/kjpp.2020.24.2.137.

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

Affiliations
  • 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu City 610072, Sichuan Province, P.R. China. chenqiu1005@cdutcm.edu.cn
  • 2Chongqing Medical and Pharmaceutical College, Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing City 401331, P.R. China. dengqinghua2000@163.com
  • 3People's Hospital of Shizhu County, Chongqing City 409100, P.R. China.

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.

Keyword

Dehydrolovastatin; Inflammation; NF-κB; Statins; Ulcerative colitis

MeSH Terms

Animals
Arthritis
Blotting, Western
Colitis, Ulcerative*
Colon
Cytokines
Dextran Sulfate
Enzyme-Linked Immunosorbent Assay
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Immunohistochemistry
Inflammation
Interleukin-10
Interleukin-17
Interleukin-6
Lovastatin*
Mice*
Peroxidase
Sulfasalazine
Ulcer*
Cytokines
Dextran Sulfate
Interleukin-10
Interleukin-17
Interleukin-6
Lovastatin
Peroxidase
Sulfasalazine
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