[Metabolomics-based insights into dryness-moistening and toxicity-attenuating mechanism of salt-processed Psoraleae Fructus in rat model of kidney-Yin deficiency].

This study aims to investigate, from the perspective of pathologic-symptom toxicology, the effects of salt processing on Psoraleae Fructus(BGZ)-induced liver injury in a rat model of kidney-Yin deficiency(Yin) and to elucidate the underlying mechanisms through metabolomics. A Yin model was established in rats and treated with BGZ or salt-processed BGZ(YBGZ). Yin manifestations were evaluated based on body weight, anal temperature, and the serum cyclic adenosine monophosphate(cAMP)/cyclic guanosine monophosphate(cGMP) ratio. Liver injury was assessed based on serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels, as well as histopathological changes of the liver. Untargeted metabolomics was employed to characterize the hepatic metabolic alterations induced by BGZ and YBGZ, and the proposed mechanisms were further validated by integrating indices related to energy metabolism and inflammatory responses. Compared with BGZ, YBGZ markedly alleviated Yin symptoms, reduced serum ALT and AST levels, and mitigated hepatic inflammatory infiltration. Metabolomic profiling identified 17 differential metabolites co-regulated by BGZ and YBGZ, mainly enriched in pathways including glycolysis/gluconeogenesis, arachidonic acid metabolism, and sphingolipid metabolism, which were closely associated with hepatic energy metabolism and inflammation. Mechanism verification showed that YBGZ significantly downregulated the expression of glucose transporter 1(GLUT1), hexokinase 2(HK2), and pyruvate kinase M2(PKM2) in the liver, and correspondingly decreased serum lactate dehydrogenase(LDH) and lactic acid(LA) levels. In addition, YBGZ suppressed the levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α), while elevating the anti-inflammatory cytokine interleukin-10(IL-10) level. Collectively, salt processing alleviates BGZ-induced liver injury under the Yin condition by modulating glycolytic metabolism and inflammatory responses in the liver.