ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Integrative Analysis of Trichosanthes kirilowii Maxim Formula Granules' Anti-Triple-Negative Breast Cancer Mechanism via Network Pharmacology, Metabolomics, and Molecular Pharmacology
Yuzhen Gao 1,2
Yan Lu 3,2
Yaping Liu 4
Fen Liu 2
Jiaqi Zhang 3
Fei Xu 5
Zongwen Ji 4
Tian Fu 6
Shulong Shi 4
Shulong Jiang 7,8
1. Clinical Medical Laboratory Center, Jining No 1 People's Hospital, Jining, China
2. Shandong University of Traditional Chinese Medicine, Jinan, China
3. Clinical Laboratory Medicine Department, Jining No 1 People's Hospital, Jining, China
4. Department of Endocrinology, Jining No 1 People's Hospital, Jining, China
5. Vascular Surgery, Jining No 1 People's Hospital, Jining, China
6. Department of Respiratory and Critical Care Medicine, Jining No 1 People's Hospital, Jining, China
7. Jining Medical University, Jining, China
8. Jining No 1 People's Hospital, Jining, China
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Abstract
Background: Triple-negative breast cancer (TNBC) urgently needs effective therapies due to limited targeted options and unfavorable outcomes. We investigated Trichosanthes kirilowii Maxim formula granules (TKM) using integrated network pharmacology, metabolomics, and molecular pharmacology to clarify potential multi-target mechanisms relevant to TNBC. Methods: Liquid chromatography coupled with mass spectrometry was employed to identify the components of TKM formula granules. Network pharmacology-based prediction was used to uncover potential mechanisms by which TKM counteracts TNBC. Potential targets were identified, and pathway enrichment analysis was performed. Subsequently, TNBC cells and 4T1 tumor-bearing mice were used to verify the molecular mechanisms of TKM. Results: We identified 151 active compounds in TKM. Through network pharmacology analysis, 214 TNBC-related targets were found, with 28 core targets, including cell cycle and apoptosis regulators MYC, TP53, AKT1, CCND1, CASP3, PIK3CA, BCL2L1, and CDC42. The compound-target-pathway-disease network showed that schisandrin binds to many treatment targets with satisfactory docking performance, especially for MYC and AKT1. Experimentally, TKM was found to significantly promote apoptosis and induce G2/M-phase cell-cycle arrest in MDA-MB-231 cells. Western blot analysis showed that TKM suppressed PI3K/AKT and Wnt/β-catenin signaling pathways. Surface plasmon resonance experiment revealed that schisandrin binds to recombinant AKT1 with an equilibrium dissociation constant (K_D) of 1.525 × 10⁻⁴ M. According to untargeted metabolomics results, TKM can regulate amino acid, glycine, serine, and threonine metabolism, mineral absorption, protein digestion and absorption, central carbon metabolism, and arginine biosynthesis to exert therapeutic effects on TNBC. All findings were consistent with predicted targets and pathways. Conclusion: This study comprehensively explores the multi-target mechanisms of TKM against TNBC using network pharmacology, molecular pharmacology, and metabolomics approaches. These findings provide a foundation for future mechanistic investigations and may support the further preclinical development of TKM-based strategies for TNBC.
Summary
Keywords
LC-MS/MS, Metabolomics, Networkpharmacology, Surface Plasmon Resonance, Trichosanthes kirilowii Maxim, Triple-negative breast cancer
Received
01 July 2025
Accepted
23 January 2026
Copyright
© 2026 Gao, Lu, Liu, Liu, Zhang, Xu, Ji, Fu, Shi and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Tian Fu; Shulong Shi; Shulong Jiang
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