Schisandrin B alleviates high-glucose diet-induced oxidative stress, inflammation, and tissue injury in zebrafish and is associated with alterations in intestinal microbiota

High-glucose diet (HGD) has been reported to alter gut microbiota and induce chronic inflammation and oxidative stress. In this study, we demonstrated that Schisandrin B (SchB) markedly attenuated HGD-induced physiological disturbances in zebrafish, with a focus on multiple tissues, including the liver, intestine, brain, and retina. The results showed that SchB attenuated oxidative stress, inflammatory responses, and tissue injury induced by HGD. SchB was associated with reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA) levels, as well as enhanced superoxide dismutase (SOD) activity. In addition, the mRNA expression levels of oxidative stress–related genes (Nrf2 and HO-1) and inflammatory markers (IL-1β, IL-8, TNF- α , and Myd88) were significantly modulated in SchB-treated groups. Intestinal microbiota analysis revealed that SchB was associated with increased microbial richness and diversity, as well as partial restoration of HGD-induced dysbiosis. Overall, these findings suggest that SchB exerts antioxidant and anti-inflammatory effects in zebrafish under high-glucose dietary conditions, and these protective effects are associated with improvements in gut microbiota structure.