Proteomic analysis reveals proteins and pathways associated with the effects of Hippophae rhamnoides L. total flavonoids on ameliorating excessive erythropoiesis in high-altitude polycythemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The total flavonoids of Hippophae rhamnoides L. (TFH) exert significant antioxidant effects against hypoxia, which decreases the hematological index of high-altitude polycythemia (HAPC) mice. However, the underlying mechanisms remain unclear.

AIM OF THE STUDY: The aim of this study was to explore the targets and pathways of TFH in inhibiting excessive erythropoiesis in HAPC mice.

MATERIALS AND

METHODS

Comprehensive techniques, including biochemical index detection, morphological examination, proteomics, and western blotting, were used to explore the targets and pathways through which TFH inhibits excessive erythropoiesis in HAPC mice.

RESULTS

Gene ontology annotation of differentially expressed proteins identified substantial enrichment in reactive oxygen species (ROS) metabolic processes, mitochondrial assembly, and aerobic oxidation. Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment in peroxisome chemicals, carcinogenesis-ROS, and oxidative phosphorylation. Western blotting demonstrated that the expression of Sestrin1 (Sesn1) and nuclear factor erythroid 2-related factor 2 (Nrf2) increased, whereas that of Kelch-like ECH-associated protein 1 (Keap1) and hypoxia-inducible factor-2 alpha (HIF-2α) decreased.

CONCLUSIONS

TFH could promote HIF-2α protein degradation by activating the Sesn1/Keap1/Nrf2 signaling pathway to scavenge ROS, thereby inhibiting erythropoietin (Epo) production.