The main active component Kaji-ichigoside F1 of the ethnic medicine Rosa roxburghii Tratt prevents acetaminophen-induced acute liver injury by modulating microbial metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Kaji-ichigoside F1 (KF1), the main active component of the Guizhou ethnic medicinal material Rosa roxburghii Tratt, is widely used in China due to its anti-inflammatory properties. However, the protective effects of KF1 against drug-induced liver injury and its potential mechanisms are not yet understood.

AIM OF THE STUDY: We aimed to investigate the effects of KF1 on acute liver injury (ALI) and explore its underlying mechanisms, particularly its role in modulating the gut microbiota to inhibit ALI development.

MATERIALS AND

METHODS

KF1 was prepared via 80 % ethanol extraction, silica gel column chromatography, and Sephadex LH-20 column chromatography. Mouse models of ALI were established using acetaminophen (APAP) treatment, with or without KF1 (5 and 10 mg/kg). 16S rRNA gene sequencing, metabolomics, and transcriptomics approaches were employed to explore the inhibitory effect of KF1 on ALI. Additionally, the role of the gut microbiota was investigated through antibiotic treatment and fecal microbiota transplantation experiments.

RESULTS

Treatment with KF1 significantly altered the gut microbiota composition, notably increasing the abundance of the probiotic Akkermansia muciniphila (A. muciniphila). Furthermore, A. muciniphila enhanced the levels of beneficial metabolites, including inosine. Notably, inosine significantly suppressed inflammatory factors and improved APAP-induced ALI. Transcriptomic analysis revealed that inosine inhibited key signaling pathways, including MAPK, PI3K-AKT, JAK-STAT3, IL-17, TNF, and cytokine-cytokine receptor interactions. Importantly, the preventive effect of KF1 is dependent on microbial mechanisms.

CONCLUSION

KF1 protects against ALI by modulating the gut microbiota and associated metabolites, thereby promoting a more favorable state and inhibiting pro-inflammatory pathways.