A novel and reactive oxygen species (ROS) responsive astaxanthin phenylboronic acid derivative (AstaD-PBA) was constructed by grafting phenylboronic acid (PBA) onto astaxanthin succinate diester (AstaD), and its chemical structure and physicochemical property were identifi ed. AstaD-PBA could effectively improve the ROS quenching ability in the lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model. Then, the bioactivity of AstaD-PBA was studied by 4 zebrafi sh ROS-responsive infl ammatory models induced by LPS, copper (Cu²⁺), high-fat diet, and dextran sodium sulfate (DSS). The results suggest that AstaD-PBA might have high biosafety and the best effect on ulcerative colitis (UC) induced by DSS. Furtherly, AstaD-PBA signifi cantly alleviated and treated weight loss and colonic shrinkage, inhibited infl ammatory cytokines, and maintained microbiota homeostasis to improve UC in C57BL/6J mice. Alistipes and Oscillibacter were expected to be considered UC marker fl ora according to the Metastats analysis and Pearson correlation Mantel test (P < 0.01) of 16S rRNA gene sequencing data. In conclusion, AstaD-PBA has been promised to be a functional compound to improve UC and maintain intestinal microbiota homeostasis.

Autophagy directly regulates the amyloid-peptides (Aβ) clearance, and its dysfunction occurs in the early pathogenesis of Alzheimer’s disease (AD). We previously reported that docosahexaenoic acid-acylated astaxanthin monoester (AST-DHA) showed neuroprotection against AD pathology. However, its in-depth mechanism and autophagic responses in AD brains are poorly understood. Herein, SH-SY5Y cells overexpressing the APP gene were established to preliminarily evaluate the actions of AST-DHA on reducing Aβ_1-42 levels and regulating autophagy. In microglial BV2 cells, AST-DHA and free astaxanthin (F-AST) recovered p62 and LC3II/I levels, and restored autophagy flux by rescuing the late phase of microglial autophagy. Notably, autophagic inhibitor bafilomycin A1 blunted the abilities of AST-DHA to reduce Aβ_1-42 and fibral Aβ, suggesting that AST-DHA probably promoted Aβ clearance in a microglial autophagy-dependent manner. Further studies in APP/PS1 mice verified that dietary AST-DHA and F-AST promoted Aβ phagocytosis via microglial autophagy. Significant decreases of Iba1 and p62 levels were observed around Aβ plaque in the hippocampus and cortex using triple fluorescence staining. Furthermore, AST-DHA exhibited superior performance over F-AST in restoring autophagic dysfunction, ameliorating Aβ burden and cognitive deficit. Our findings suggest a possible mechanism of AST-DHA in improving AD by which it restores microglial autophagy to facilitate cerebral Aβ clearance. It supports the future application of AST-DHA as an autophagic regulator in maintaining brain function.