Plateau zokors (Eospalax baileyi) respond to secondary metabolites from the roots of Stellera chamaejasme by enhancing hepatic inflammatory factors and metabolic pathway genes.

Herbivores rarely consume toxic plants. An increase in the proportion of toxic plant secondary metabolites (PSMs) in poisonous plants can promote detoxification and related metabolic capacity of animals. Poisonous plants with thick taproots like Stellera chamaejasme (SC) are important stored food for the plateau zokor (Eospalax baileyi) during the winter and promote the development of detoxification mechanisms in this animal. In this study, plateau zokors were administered gavages of 0.2, 1.05, and 2.10 ml/kg SC water extracts. Serum samples were collected from plateau zokors to measure the levels of transaminases and oxidative stress. Transcriptome analysis was conducted to evaluate the differential genes of multiple metabolic pathways to investigate the relationship between the physiological processes and metabolic adaptation capacity of these animals in response to SC. After SC administration, plateau zokors showed significant hepatic granular degeneration and inflammatory reactions in the liver and aspartate aminotransferase, alanine aminotransferase, and malondialdehyde levels increased in a dose-dependent manner. Further, differential expression was also found in the plateau zokor livers, with most enrichment in inflammation and detoxification metabolism pathways. The metabolic adaptation responses in P450 xenobiotic clearance, bile secretion, and pancreatic secretion (Gusb, Hmgcr, Gstm1, Gstp1, and Eobag004630005095) were verified by mRNA network analysis as key factors related to the mechanism. Plateau zokors respond to SC PSMs through changes in liver physiology, biochemistry, and genes in multiple metabolic pathways, validating our hypothesis that plateau zokors can metabolize PSMs when they ingest toxic plants.