Pi3k/akt/mtor Signaling in Cancer · Journal article
Biomedical Chromatography · August 17, 2026
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This is a preclinical metabolomics-guided natural product discovery study in which two Polygonum species showed metabolome heterogeneity and selective extracts (PB-EA and PV-NB) inhibited triple-negative breast cancer cell lines in vitro and suppressed tumor growth in a mouse xenograft model. An isolated compound (crataegunin D) demonstrated IC50 values of 20.65–24.91 μM against human and murine TNBC cells and showed predicted binding to EGFR and CDK receptors, but no mechanism, safety, or efficacy data in humans are provided.
Preclinical metabolomics-guided phytochemical isolation and bioactivity screening with molecular docking. Two wild plant species (Polygonum bistorta and Polygonum viviparum) evaluated for antibreast cancer metabolome composition and activity. Cell-based studies used murine 4T1 TNBC cells and human MDA-MB-231 cells. Animal studies used 4T1-Luc orthotopic xenograft mouse model.. Intervention: Ethyl acetate extract of P. bistorta (PB-EA) and n-butanol extract of P. viviparum (PV-NB); isolated compound crataegunin D and 7 other phytochemicals.. Compared with: Model control groups (in vivo); untreated cells (in vitro).. Not stated..
Phytochemical analysis identified 209 metabolites across two Polygonum species, with flavonoids (45 compounds) predominant. PB-EA and PV-NB extracts showed strongest cytotoxicity with IC50 values of 23.28 ± 0.90 and 39.11 ± 2.36 μg/mL against 4T1 cells. Both extracts significantly suppressed tumor growth in 4T1-Luc orthotopic xenograft model (p < 0.001, p < 0.01).
No toxicity, pharmacokinetics, or in vivo safety data provided for isolated compounds. PB-EA and PV-NB extracts showed strongest cytotoxicity with IC50 values of 23.28 ± 0.90 and 39.11 ± 2.36 μg/mL against 4T1 cells.
This work identifies promising natural product leads for TNBC but remains at the preclinical stage; crataegunin D and related compounds warrant further mechanistic validation and safety profiling before any clinical translation. The metabolome heterogeneity between plant species is noteworthy for natural product chemistry but does not yet inform clinical practice.
Early-stage natural product discovery using in vitro and mouse xenograft models with molecular docking; results are promising but preclinical and lack human data or regulatory validation.
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This work identifies promising natural product leads for TNBC but remains at the preclinical stage; crataegunin D and related compounds warrant further mechanistic validation and safety profiling before any clinical translation. The metabolome heterogeneity between plant species is noteworthy for natural product chemistry but does not yet inform clinical practice.
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ABSTRACT The rise of triple‐negative breast cancer (TNBC) warrants the urgent need to identify novel therapies. Herein, untargeted metabolomics‐guided isolation revealed the metabolome fingerprints of Polygonum bistorta (PB) and Polygonum viviparum (PV) in correlation with their TNBC inhibitory activity. Phytochemical analysis annotated 209 metabolites, with flavonoids (45 compounds) as the major class, followed by phenolic acids (25), tannins (24), and hydroxycinnamic acids (18). Multivariate data analysis identified chlorogenic acid, 6‐ O ‐galloylarbutin, and procyanidin B1 as key markers of PV, whereas naringenin‐ O ‐glucoside, catechin, and crataegunin D characterized PB. Among different polar extracts, ethyl acetate extract of PB (PB‐EA) and the n ‐butanol extract of PV (PV‐NB) exhibited the strongest cytotoxicity against 4T1 cells, with IC 50 values of 23.28 ± 0.90 and 39.11 ± 2.36 μg/mL, respectively. Subsequently, the same extracts significantly suppressed tumor growth in the 4T1‐Luc orthotopic xenograft mouse model compared with their respective model groups ( p < 0.001, p < 0.01). Bioassay‐guided isolation yielded 8 compounds, including crataegunin D, which isolated from Polygonaceae plants for the first time, displaying IC 50 values of 24.91 ± 2.43 and 20.65 ± 1.77 μM against 4T1 and MDA‐MB‐231 cells, respectively. Molecular docking revealed binding free energies (ΔG) ranging from −52 to −48 kcal/mol targeting EGFR and CDK receptors.
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