Elucidating the molecular mechanisms of the mongolian medicine Ana Gaqi Nari in gastric cancer treatment through a multi-omics-guided experimental validation.

BACKGROUND

Gastric cancer (GC) remains a global health challenge with limited therapeutic options, highlighting the need for novel treatments. Traditional Mongolian medicine Ana Gaqi Nari (AGN) offers promising anti-cancer potential, but its molecular mechanisms remain poorly understood. Multi-omics approaches provide an unprecedented opportunities to decode complex herbal formulations and bridge traditional knowledge with modern systems biology.

PURPOSE: To elucidate AGN's molecular mechanisms in GC treatment using an integrative strategy combining network pharmacology, multi-omics analyses, and experimental validation, while identifying bioactive compounds and therapeutic targets.

METHODS

We employed integrative multi-omics approaches to predict AGN's bioactive components and targets, followed by molecular docking and binding assays. In vitro and in vivo models assessed AGN's effects on apoptosis, pyroptosis, and pro-survival pathways. Multi-omics profiling characterized AGN's impact on GC metabolism and inflammation. Xenograft studies compared AGN's efficacy and safety to standard chemotherapy.

RESULTS

Multi-omics analysis identified piperine as AGN's primary bioactive compound, exhibitING strong binding to d-amino acid oxidase (DAO) (-10.3 kcal/mol), a novel GC target associated with poor prognosis. AGN demonstrated dual anti-cancer effects by inducing both apoptosis and pyroptosis while suppressing pro-survival AKT/ERK signaling. AGN remodeled amino acid and lipid metabolism, disrupting GC's metabolic plasticity, and antagonized IL-17A-mediated inflammation. In xenograft models, AGN showed dose-dependent tumor suppression comparable to standard chemotherapy with superior safety profiles. DAO and IL-17A emerged as potential biomarkers for patient stratification.

CONCLUSION

This study reveals AGN as a multi-target GC therapy DAO modulation, IL-17A suppression, metabolic reprogramming, and programmed cell death induction. By integrating multi-omics and ethnopharmacology, we provide a framework for modernizing traditional herbal medicines into evidence-based therapies, positioning AGN as a potential candidate for precision GC treatment.