Cinobufacini Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Inhibiting M1 Macrophage Polarization.

Abstract

Cinobufacini is a traditional Chinese medicine used clinically that has antitumor and anti-inflammatory effects. It improves colitis outcomes in the clinical setting, but the mechanism underlying its function yet to be uncovered. We investigated the protective effects and mechanisms of cinobufacini on colitis using a dextran sulfate sodium (DSS)-induced colitis mouse model, mainly focusing on the impact of macrophage polarization. Our results showed that cinobufacini dramatically ameliorated DSS-induced colitis in mice. Cinobufacini treatment reduced the infiltration of activated F4/80+ and/or CD68+ macrophages into the colon in DSS-induced colitis mice. More importantly, cinobufacini significantly decreased the quantity of M1 macrophages and the expression of proinflammatory cytokines such as interleukin-6, tumor necrosis factor α, and inducible nitric oxide synthase. Cinobufacini also increased the population of M2 macrophages and the expression of anti-inflammatory factors such as interleukin-10 and arginase-1 in DSS-induced colitis mice. Furthermore, our study demonstrated that cinobufacini inhibited M1 macrophage polarization in lipopolysaccharide-induced RAW 264.7 cells. Mechanistically, our in vivo and in vitro results showed that cinobufacini inhibition of M1 macrophage polarization may be associated with the suppression of nuclear factor κB activation. Our study suggests that cinobufacini could ameliorate DSS-induced colitis in mice by inhibiting M1 macrophage polarization.

• Authors: Si-Wei Wang, Yong-Feng Bai, Yuan-Yuan Weng, Xue-Yu Fan, Hui Huang, Fang Zheng, Yi Xu, Feng Zhang
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 368 Issue 3 Pg. 391-400 (03 2019) ISSN: 1521-0103 [Electronic] United States
• PMID: 30606760 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.

Chemical References

• Amphibian Venoms
• Inflammation Mediators
• huachansu
• Dextran Sulfate

Topics

• Amphibian Venoms (pharmacology, therapeutic use)
• Animals
• Cell Polarity (drug effects, physiology)
• Colitis (chemically induced, drug therapy)
• Dextran Sulfate (toxicity)
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Macrophages (drug effects, metabolism)
• Male
• Medicine, Chinese Traditional (methods)
• Mice
• Mice, Inbred ICR
• RAW 264.7 Cells