Mechanistic study of a triterpenoid-enriched fraction derived from Cynomorium songaricum against NAFLD: An integrative elucidation.

BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is a growing global health concern linked to metabolic dysfunction and inflammation. Traditional Chinese Medicine (TCM), with its emphasis on restoring balance and harmony within the body, is well-suited to address the heterogeneity of NAFLD. Effective strategies to manage NAFLD remain limited, emphasizing the need for novel bioactive compounds with therapeutic potential.

PURPOSE: This study aimed to investigate the protective effects of a triterpenoid-enriched fraction (CST) derived from Cynomorium songaricum and its active compounds on NAFLD and to elucidate their underlying mechanisms.

METHODS

CST composition was analyzed using UHPLC/ESI-LTQ-Orbitrap-MS. Anti-inflammatory and lipid-lowering effects were assessed through in vitro and in vivo experiments. Integration of RNA-seq and novel network pharmacology identified key molecular targets, while molecular docking confirmed interactions of oleanolic acid (OLA) and ursolic acid (UA) with IKBKB and TACE, crucial components of the NF-κB pathway.

RESULTS

CST, OLA and UA significantly reduced lipid accumulation and downregulated inflammatory markers, including TNF-α and lipogenesis-related genes in vitro. In vivo, these compounds reduced lipid accumulation and modulated NF-κB activation, demonstrating robust anti-inflammatory and lipid-regulating effects.

CONCLUSION

CST exhibits promising bioactive properties in managing NAFLD. IKBKB and TACE mediate CST's protective effects against NAFLD by suppressing NF-κB target genes, reducing TNF-α, and inhibiting lipogenesis. These findings provide a foundation for developing CST and its active components, OLA and UA, as potential therapeutic agents for NAFLD.