Comparative Analysis of the Antioxidant, Antidiabetic, Antibacterial, Cytoprotective Potential and Metabolite Profile of Two Endophytic Penicillium spp

The current study assessed the metabolite abundance, alpha (α)-amylase and α-glucosidase inhibitory, antioxidant, and antibacterial activity of the ethyl acetate extract (EAE) of endophytic (PL) and (PR). A higher extract yield was found in EAE-PR with a total phenolic content of 119.87 ± 3.74 mg of GAE/g DW and a total flavonoid content of 16.26 ± 1.95 mg of QE/g DW. The EAE-PR inhibited α-amylase and scavenged ABTS+ radicals with a half-maximal inhibitory concentration (IC ) of 362.5 and 37.5 µg/mL, respectively. Compared with EAE-PL, EAE-PR exhibited higher antibacterial activity against Gram-positive and Gram-negative pathogens. Treatment with EAE-PR (1000 µg/mL) did not cause significant toxicity in the HEK-293 cell line compared to the control cells ( < 0.05). EAE-PR treatments (250-1000 µg/mL) showed higher cytoprotective effects toward H O -stressed HEK-293 cells compared with ascorbic acid (AA). The UHPLC-Q-TOF-MS/MS analysis revealed the presence of thiophene A (C H S), limonene (C H ), and phenylacetic acid (C H O ) in EAE-PR. Furthermore, these compounds demonstrated substantial interactions with diabetes (α-amylase and α-glucosidase), oxidative stress (NADPH-oxidase), and bacteria (D-alanine D-alanine ligase)-related enzymes/proteins evidenced in silico molecular docking analysis.