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

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

  • Phytomedicine. 2025 Nov 26:150:157623. doi: 10.1016/j.phymed.2025.157623.
Rui Li 1,  Boyu Pan 2,  Zeyang Liu 3,  Runfang Wang 4,  Xiaofeng Wang 5,  Shihui Cao 1,  Jie Zhang 6,  Bao Jin 7,  Liren Liu 8,  Chunnuan Wu 9
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
  • 2 Department of molecular pharmacology, Tianjin Medical University Cancer Institute and Hospital，National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
  • 3 Department of pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
  • 4 Otolaryngology department, Xilingol Mongolian Hospital, Xilinhot, Inner Mongolia Autonomous Region 026300, China.
  • 5 Department of Clinical Pharmacy, Xilingol Mongolian Hospital, Xilinhot, Inner Mongolia Autonomous Region 026300, China.
  • 6 Department of pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China. Electronic address: [email protected].
  • 7 Administrative department, Xilingol Mongolian Hospital, Xilinhot, Inner Mongolia Autonomous Region 026300, China. Electronic address: [email protected].
  • 8 Department of molecular pharmacology, Tianjin Medical University Cancer Institute and Hospital，National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. Electronic address: [email protected].
  • 9 Department of pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China. Electronic address: [email protected].
PMID: 41330183 DOI: 10.1016/j.phymed.2025.157623
Abstract

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.

Keywords

Ana Gaqi Nari (AGN); Gastric cancer (GC); Mongolian medicine; Multi-omics; Network Pharmacology.

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