Antioxidant, anti-inflammatory, cytotoxicity and larvicidal activities of Ziziphus oenopolia leaves: in vitro and in silico studies

The present study investigated the phytochemical composition, in vitro and in silico biological activities, and insecticidal properties of Ziziphus oenopolia (L) Mill. leaf extracts. The LC-MS profile of Ziziphus oenopolia leaves extract, which identified major phytochemical classes of fatty acids, flavonoids, and phenolic acids. The GC-MS profile, including n-hexadecanoic acid, phytol, and 9,12,15-octadecatrienoic acid, which were predicted by PASS and ADMET profiling to exhibit strong antioxidant, anti-inflammatory, cytotoxic, and larvicidal activities. The hydroalcoholic extract demonstrated the highest biological efficacy across multiple assays. In vitro antioxidant evaluation revealed strong DPPH and ABTS radical scavenging activities with IC₅₀ values of 41.04 and 43.54 µg/mL, respectively. The extract also showed significant protein anti-denaturation effects against bovine serum albumin and egg albumin (IC₅₀ = 315.53 and 311.60 µg/mL), significant cytotoxicity (EC₅₀ = 173.92 µg/mL), and strong larvicidal activity (LC₅₀ = 126.09 µg/mL for Aedes aegypti and 136.01 µg/mL for Tribolium castaneum ), all exhibiting dose-dependent inhibition. In silico molecular docking further supported these findings, revealing strong binding affinities of the phytoconstituents toward human peroxiredoxin 5 as an antioxidant target, COX-2 (PDB: 1PXX) as an anti-inflammatory target, EGFR (PDB: 2EB3) as an anticancer target, and juvenile hormone binding protein (PDB: 5V13) as a larvicidal target. Overall, Z. oenopolia may contribute to the development of natural antioxidants and anti-inflammatory agents for mitigating oxidative stress-related and chronic inflammatory diseases.