Therapeutic and Safety Evaluation of Enhydra fluctuans Lour. and Ipomoea aquatica Forssk. as Acetylcholinesterase, Butyrylcholinesterase, β‐Secretase, and CytochromeP450 Inhibitors Using In Vitro and UPLC–QTOF–MS‐Based Molecular Docking and Dynamic Simulation Study

Considering the multi‐targeted drug approach, Enhydra fluctuans and Ipomoea aquatica were comprehensively investigated for their acetylcholinesterase, butyrylcholinesterase, and β‐secretase enzyme inhibitory potential, which are linked to Alzheimer's disease. The results showed that I. aquatica produced more prominent anti‐cholinesterase potential compared to E. fluctuans . But E. fluctuans showed more potent BACE1 inhibitory potential compared to I. aquatica . For the safety study, the extracts were tested for heavy metal content estimation, CYP450 isozyme inhibitory potential, and cytotoxicity in human hepatocellular carcinoma cells. Antioxidant capacity, total phenolics, and total flavonoids were significantly correlated with the anti‐cholinesterase activity, where I. aquatica showed more protuberant potential compared to E. fluctuans . The UPLC–QTOF–MS analysis tentatively identified phytometabolites from the phenylethanoid glycosides and chlorogenic acids class in both the extracts. Further, in silico toxicity prediction, molecular docking, and dynamic simulation studies provided additional evidence on the safety profile and interaction potential of phytometabolites with AChE, BChE, and BACE1 enzymes.