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 (alpha)-amylase and alpha-glucosidase inhibitory, antioxidant, and antibacterial activity of the ethyl acetate extract (EAE) of endophytic Penicillium lanosum (PL) and Penicillium radiatolobatum (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 alpha-amylase and scavenged ABTS+ radicals with a half-maximal inhibitory concentration (IC50) of 362.5 and 37.5 mu g/mL, respectively. Compared with EAE-PL, EAE-PR exhibited higher antibacterial activity against Gram-positive and Gram-negative pathogens. Treatment with EAE-PR (1000 mu g/mL) did not cause significant toxicity in the HEK-293 cell line compared to the control cells (p < 0.05). EAE-PR treatments (250-1000 mu g/mL) showed higher cytoprotective effects toward H2O2-stressed HEK-293 cells compared with ascorbic acid (AA). The UHPLC-Q-TOF-MS/MS analysis revealed the presence of thiophene A (C13H8S), limonene (C10H16), and phenylacetic acid (C8H8O2) in EAE-PR. Furthermore, these compounds demonstrated substantial interactions with diabetes (alpha-amylase and alpha-glucosidase), oxidative stress (NADPH-oxidase), and bacteria (D-alanine D-alanine ligase)-related enzymes/proteins evidenced in silico molecular docking analysis.