Comparison of Neuroprotection and Regulating Properties on Gut Microbiota between Selenopeptide Val-Pro-Arg-Lys-Leu-SeMet and Its Native Peptide Val-Pro-Arg-Lys-Leu-Met In Vitro and In Vivo

作者：Wu, Shujian; Zhu, Zhenjun; Chen, Mengfei; Huang, Aohuan; Xie, Yizhen; Hu, Huiping; Zhang, Jumei; Wu, Qingping; Wang, Juan^*; Ding, Yu^*

来源：Journal of Agricultural and Food Chemistry, 2023, 71(32): 12203-12215.

DOI：10.1021/acs.jafc.3c02918

• selenopeptide
• native peptide
• neuroinflammation
• gut microbiota
• metabolite

Selenopeptides are promising candidates for interveningin neuroinflammation;however, the key role of selenium (Se) in selenopeptides remains poorlyunderstood. To address this gap, we compared the neuroprotective effectsof selenopeptide Val-Pro-Arg-Lys-Leu-SeMet (namely, Se-P1)and its native peptide Val-Pro-Arg-Lys-Leu-Met (namely, P1). Our resultsdemonstrate that Se-P1 treatment exhibits superior antioxidantand antineuroinflammatory effects in PC12 cells and lipopolysaccharide(LPS)-injured mice compared to P1. Moreover, the administration ofSe-P1 and P1 resulted in a shift in the gut microbiota composition.Notably, during LPS-induced injury, Se-P1 treatment demonstratedgreater stability in maintaining gut microbiota composition comparedto P1 treatment. Specifically, Se-P1 may have a positive impacton gut microbiota dysbiosis by modulating inflammatory-related bacteriasuch as enhancing Lactobacillus abundancewhile reducing that of Lachnospiraceae_NK4A136_group. Furthermore, the alteration of metabolites induced by Se-P1treatment exhibited a significant correlation with gut microbiota,subsequently modulating the inflammatory-related metabolic pathwaysincluding histidine metabolism, lysine degradation, and purine metabolism.These findings suggest that organic Se contributes to the bioactivitiesof Se-P1 in mitigating neuroinflammation in LPS-injured micecompared to P1. These findings hold significant value for the developmentof potential preventive or therapeutic strategies against neurodegenerativediseases and introduce novel concepts in selenopeptide nutrition andsupplementation recommendations.

• 单位
  y; 华南农业大学