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 1 and/or CD68 1 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 a, 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 kB activation. Our study suggests that cinobufacini could ameliorate DSS-induced colitis in mice by inhibiting M1 macrophage polarization.

Excretory/Secretory Products From Trichinella spiralis Adult Worms Attenuated DSS-Induced Colitis in Mice by Driving PD-1-Mediated M2 Macrophage Polarization

“…Activated macrophages are functionally divided into two main categories: the M1 type (the classical-activated macrophage) and the M2 type (the alternatively activated macrophage) (11). Although M1-type macrophages release proinflammatory cytokines and enhance inflammatory responses, they also cause injury to host tissue (12). On the contrary, M2-type macrophages release antiinflammatory cytokines and help maintain tissue immune homeostasis, thus avoiding overactive inflammation (13,14).…”

Cinobufacini ameliorates experimental colitis via modulating the composition of gut microbiota

“…Cinobufacini (Huachansu), an aqueous extract from the skin of the Bufo toad, is a traditional Chinese medicine widely used in clinic with anti-tumor and anti-inflammatory effects[10]. In previous study, our team found that cinobufacini could relief DSS-induced colitis in mice[11], but the underlying mechanism is still elusive. Bufadienolides, the principal bioactive components of cinobufacini, have been reported to have strong antimicrobial activity in vitro[12].…”

Neohesperidin enhances PGC-1α-mediated mitochondrial biogenesis and alleviates hepatic steatosis in high fat diet fed mice

“…The liver tissues sections were deparrafinized and antigen retrieval were also performed as previously described 19 . MaxVision HRP-Polymer antiRabbit IHC Kit (MXB Biotechnologies, Fuzhou, China) was used to develop signal.…”

“…The protein extraction method was according to our previous study 19 , 22 . Equal amounts of proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).…”