Abstract: In this study, rare ginsenosides were obtained by enzymatic transformation of ginsenosides using β-glucosidase and were quantitatively analyzed. In addition, their protective effects against carbon tetrachloride (CCl4)-induced liver injury in mice were investigated. High performance liquid chromatography (HPLC) analysis indicated a substantial increase in rare ginsenoside content after enzymatic treatment, with the formation of new ginsenosides Rh1 and Rg6. Animal studies showed that administration of rare ginsenosides significantly attenuated CCl4-induced histopathological alterations in hepatic tissues. Western blot analysis further revealed that a high dose of rare ginsenosides exerted hepatoprotective effects through marked upregulation of peroxisome proliferator-activated receptor alpha (PPARα) expression and concurrent downregulation of proprotein convertase subtilisin/kexin type 9 (PCSK9), cytochrome P450 2E1 (CYP2E1) and cytochrome P450 1A2 (CYP1A2). Additionally, the high dose of rare ginsenosides modulated the gut microbiota composition by suppressing the proliferation of harmful bacteria (Bacteroidetes and Proteobacteria), enhancing the growth of beneficial bacteria (Allobaculum and Lactobacillus) within the Firmicutes phylum, and significantly elevating the Firmicutes/Bacteroidetes (F/B) ratio, ultimately restoring gut microbial homeostasis. In summary, these findings demonstrate that β-glucosidase-derived rare ginsenosides can effectively mitigate CCl4-induced hepatic injury in mice.

Key words: ginseng; rare ginsenosides; enzymatic transformation; chemical liver injury; gut microbiota