Chemical exploration of different extracts from Phytolacca americana leaves and their potential utilization for global health problems: in silico and network pharmacology validation

Phytolacca americana L. is of great interest as a traditional additive in various folk remedies in several countries, including Turkey. We aimed to determine the chemical profile (assisted by high-Performance liquid chromatography-electrospray ionization-tandem mass apectrometry (HPLC-ESI-MS/MS) experiments of three extracts obtained by different polarity solvents viz. ethyl acetate (to extract semipolar compounds), methanol and water (to extract highly polar metabolites) from P. americana leaves. Their anti-diabetic effects were investigated in vitro by assessing their inhibition toα-amylase and α-glucosidase. Assessment of the neuroprotective potential of the three extracts was carried out against acetyl-(AChE) and butyryl-(BChE) cholinesterase enzymes. HPLC-ESI-MS/MS experiments showed a total of 17 chromatographic peaks primarily classified to six flavonoids, two saponins, and six fatty acids. Antioxidant assays revealed remarkable activity for the ethyl acetate and methanol extracts. The BChE inhibition was considerably more significant (4.08 mg galantamine equivalent (GALAE)/g) for the ethyl acetate extract, whereas the methanol extract had good inhibitory efficacy for AChE (2.05 mg GALAE/g). Through network pharmacology, the compounds’ mechanism of action of targeted key gene in their associated diseases were identified. The hubb gene signal transducer and activator of transcription 3 (STAT3) and tumour necrosis factor (TNFα) where the P. americana compound’s site of action in inflammation bowel disease. The results offer possibilities for the prospective application of P. americana in metabolic regulation, blood glucose control, and as a source of bioactive compounds with cholinesterase enzyme inhibitory characteristics which could be of relevance in the cosmetic or pharmaceutical industry for combating melanogenesis.