A Highly Potent and Selective Histone Deacetylase 6 Inhibitor Prevents DSS-Induced Colitis in Mice.
Inflammatory bowel disease (IBD) is a refractory illness with remarkably increasing incidence rate all over the world. However, no desirable treatment scheme is available. Therefore, research and development of new drugs for treating IBD are urgently needed. Histone deacetylase 6 (HDAC6) is considered to be a pro-inflammatory factor, thus the inhibitors specifically-targeting HDAC6 may find their way in IBD treatment. In this study, we evaluated the anti-inflammatory activity of a novel potent and selective HDAC6 inhibitor, LTB2, in dextran sulfate sodium (DSS)-induced colitis mouse model. It was found that LTB2 treatment significantly alleviated DSS-induced colitis in mice, as evidenced by body weight, colon length, histological examination, and the disease activity index (DAI) scores of rectal bleeding and diarrhea. More importantly, it showed a better protective effect on the DSS-induced colitis mice than the commonly used mesalazine in the clinic. Our results demonstrated that selective HDAC6 inhibitors may have a good prospect for IBD treatment.
School of Pharmacy, Second Military Medical University.
Ting
T
Liu
School of Pharmacy, Second Military Medical University.
Renping
R
Wang
School of Pharmacy, Second Military Medical University.
Haojie
H
Xu
School of Pharmacy, Second Military Medical University.
Yunlong
Y
Song
School of Pharmacy, Second Military Medical University.
Yunpeng
Y
Qi
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D016264:Dextran Sulfate; D000073864:Histone Deacetylase 6 / Q000037:antagonists & inhibitors*; D008297:Male; D008810:Mice, Inbred C57BL
D000893:Anti-Inflammatory Agents; D016264:Dextran Sulfate; D000073864:Histone Deacetylase 6
anti-inflammatory activity; colitis; histone deacetylase 6 inhibitor; inflammatory bowel disease