Bixin ameliorates high fat diet-induced cardiac injury in mice through inflammation and oxidative stress suppression

Diabetic cardiomyopathy is known as an essential complication of diabetes, a main reason leading to mortality for diabetic patients, and novel therapeutic strategies for treatment are urgently required. Bixin (BX), isolated from the seeds of Bixa orellana, is a carotenoid, possessing anti-inflammatory, anti-tumor and anti-oxidant activities. In our study, we attempted to calculate the role of bixin in cardiac injury progression, and reveal the possible molecular mechanism. Bixin treatment ameliorated cardiac dysfunction through inhibiting fibrosis, inflammation and Reactive Oxygen Species (ROS) generation. It reduced fibrosis levels via collagen deposition down-regulation. Inflammatory response was attenuated by reducing pro-inflammatory cytokines secretion via Toll-like Receptor 4/nuclear factor kappa B (TLR4/NF-κB) signaling pathway inactivation in mice induced by high fat diet. Also, in in vitro studies, lipopolysaccharide (LPS)-treated cardiac muscle cells exhibits pro-inflammatory cytokines over-expression, which was reduced by bixin through blocking TLR4/NF-κB pathway. Additionally, oxidative stress triggered by high fat in vivo and LPS in vitro was down-regulated for bixin administration via nuclear factor-E2-related factor 2 (Nrf2) signaling pathway activation. Our study suggested that bixin might be a novel and protective agent with therapeutic activity against cardiac injury by suppressing fibrosis, inflammation and oxidative stress.