Therapeutic effects of Saussurea graminea Dunn and its active compounds in sepsis-associated liver injury: Transcriptomics, metabolomics and experimental validation.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea graminea Dunn (SG), a traditional Chinese medicinal herb known as "Za Chi" in Tibet of China, is frequently utilized in the treatment of inflammatory diseases such as hepatitis. However, the active ingredients and mechanism of its therapeutic effect on Sepsis - associated liver injury (SALI) remain unclear. AIM OF THE STUDY: To elucidate the effect of SG in combating SALI, uncover its mechanism of action, and explore possible active compounds. MATERIALS AND METHODS: We established a SALI model by intraperitoneal injection of lipopolysaccharide to assess the efficacy of SG. Transcriptomics and metabolomics were employed to reveal its possible mechanism of action. Subsequently, Western blot, flow cytometry, confocal microscopy, quantitative PCR, HPLC-MS, and molecular docking were utilized to verify its mechanism and active ingredients. RESULTS: SG effectively counteracts SALI by inhibiting the cytokine storm. Transcriptomics indicates that SG regulates SALI through mitochondrial/TNF and metabolic pathways. Metabolomics demonstrates that arachidonic acid metabolism is involved in the process of SG treating SALI. HPLC-MS identified the main components of SG as chlorogenic acid, syringin, scopoletin, rutin, isochlorogenic acid, and narcissin, and these six compounds were confirmed as potential active components in the RAW264.7 inflammation model. CONCLUSION: SG and its active ingredients play a role in alleviating SALI by reducing the cytokine storm through mtDNA/TNF/arachidonic acid metabolism.