Alleviation of excessive intestinal reactive oxygen species induced by circadian rhythm disruption through the Astaxanthin@Spirulina platensis complex

Circadian rhythm plays a crucial role in maintaining intestinal homeostasis, and conversely, the remodeling of gut microbiota can help regulate circadian rhythm. Although traditional therapeutic strategies involving oral small-molecule drugs can modulate the intestinal health in circadian rhythm disruption (CRD), they are limited by restricted efficacy, dependence, and side effects. Herein, astaxanthin (AXT) and Spirulina platensis (SP) were used to prepare an innovative complex (AXT@SP) by a simple one-step synthesis method to alleviate the excessive intestinal reactive oxygen species (ROS) in CRD. The AXT@SP successfully achieved efficient loading of AXT with the drug loading efficiency of 34.56% and extended the retention time of AXT in the intestine for more than 12 h. As expected, AXT@SP reduced the intestinal ROS generation by 40.7%, restored the circadian oscillation of antioxidant-related indicators, protected the intestinal immune barrier, and reshaped the gut microbiota composition in the intestine of CRD mice. Importantly, AXT@SP restored the circadian peak of γ-aminobutyric acid during the physiological sleeping phase and regulated the phase advance of cortisol at ZT12. Our results suggested that AXT@SP could be exploited as a promising strategy for regulating CRD-related intestinal homeostasis via the gut-brain axis.