Metabolite Profiling and Network Pharmacology of Persimmon Vinegar (Diospyros kaki) Compounds, with in silico Validation for Non-Small Cell Lung Cancer Therapy.

objectiveNon-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, with complex mechanisms, drug resistance, and significant side effects from conventional chemotherapy, all of which hinder effective treatment. Diospyros kaki (persimmon) vinegar, produced through spontaneous fermentation, has enhanced flavonoid content that may increase its pharmacological activity; however, its molecular mechanisms against NSCLC remain unclear. This is the first study to map the molecular mechanisms of persimmon vinegar compounds against NSCLC by integrating metabolite profiling, network pharmacology, and molecular docking validation.

methodsCompounds were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and screened for pharmacological properties, followed by network pharmacology and molecular docking to explore potential targets against NSCLC.

resultTwenty-two compounds were identified, with three key compounds benzoyl arginine amine, indoline, and exocarpic acid, implicated in the NSCLC pathway (hsa05223). Twenty-seven target genes were associated with this pathway. Benzoyl arginine amine exhibited a binding affinity of -86.9707 kcal/mol for CDK6 (PDB ID: 8I0M) and -120.017 kcal/mol for HRAS (PDB ID: 3K8Y), greater than their native ligand, suggesting its potential to inhibit CDK6 activity, block the G1/S phase transition, and suppress cancer cell proliferation via the E2F pathway. Its interaction with HRAS may inhibit the MAPK pathway, which is critical for cancer progression.

conclusionThese findings provide preliminary evidence for the potential of persimmon vinegar compounds as leads for NSCLC drug development, warranting further in vitro and in vivo studies.