Abstract
In the current study, a synthetic vinegar solvent (10% acetic acid) was employed to extract bioactive contents of Silybum marianum, and further in-vitro and in-silico methods were validated to authenticate its pharmacological behavior. The GC-MS profiling of Vinegar extract of Silybum marianum (VESM) revealed a diverse array of bioactives, including polyphenols, alkaloids, fatty acids, and sugar derivatives. According to the results of the DPPH assay, VESM exhibited strong antioxidant potential (67.6 ± 0.76%) that was nearly equivalent to the synthetic antioxidant BHA (65.1 ± 0.71%). The antimicrobial activity of VESM demonstrated higher inhibitory activity against Aspergillus fumigatus (36 ± 0.41 mm) and Staphylococcus aureus (27 ± 0.3 mm) as compared to fluconazole (21 ± 0.79) and gentamicin (19 ± 0.81), respectively. Furthermore, α-amylase inhibition assays revealed significant antidiabetic activity (61.31 ± 1.81%), compared to acarbose. In-silico molecular docking studies highlighted strong binding interactions between major polyphenols-particularly Phenol, 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methyl]-and target enzymes involved in microbial infection and glucose metabolism. The findings of this study clearly validate the pharmacological potential of VESM and support its application as a multifunctional, sustainable nutraceutical or herbal remedy for mitigating oxidative stress, microbial infections, and diabetes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-026-00553-3.