Pharmacological Potential of Fraxinus hookeri and Its Essential Oil: An Integrated In Vitro and In Silico Investigation of Antioxidant, DNA-Protective and Cytotoxic Effects

Genus Fraxinusspecies has a long history in folk medicine worldwide, being utilized to address a wide array of pharmacological conditions, including anti-cancer, anti-diabetic, rheumatic pain, neuroprotective, immunosuppressive, anti-inflammatory and anti-obesity properties. Given the widespread regional application of Fraxinus for therapeutic purposes, this research, for the first time, explored the in vitro activities of F. hookeri fractions and analyzed their essential oil composition. The oils were analyzed by GC-MS for phytochemical composition. Cytotoxicity against Artemia salina and A-549 and HepG2 cell lines was assessed using the MTT assay. The antioxidant potential was evaluated with the DPPH assay and genotoxicity was tested on H2O2-induced DNA damage in human lymphocytes using the Comet assay. The compounds' interactions with BCL2 and EGFR were determined using molecular docking. GC-MS analysis identified 12 bioactive phytochemicals, with linoleic acid ethyl ester (34.46%) being the most abundant, followed by 9,12-octadecadienoic acid (17.21%), nn-Hexadecanoic acid (8.12%), hexadecanoic acid ethyl ester (7.41%). The MTT assay revealed significant growth inhibition of human hepatocellular and lung carcinoma cell lines, with IC50 values for FHNH at 113 +/- 2.87 mu mu g/mL and 120 +/- 2.96 mu mu g/mL. FHCF and FHNH showed high cytotoxicity against brine shrimps, with mortality rates of 80% and 73% at 1000 mu mu g/mL, respectively. FHME demonstrated the highest DPPH scavenging ability (70.64 +/- 3.03%). FHNH showed the highest protective efficacy against H2O2-induced DNA damage in lymphocytes, with significantly lower DNA damage (tail-DNA length 3 +/- 0.54 mu mu m) than control. nn-Hexadecanoic acid and 9,12-Octadecadienoic acid were the best-docked ligands with BCL2 and EGFR. F. hookeri exhibits significant antioxidant, genotoxic and cytotoxic activities, making it a promising candidate for anticancer strategies and pharmacological applications. Its essential oils contain bioactive components valuable for nutraceuticals and biomedical uses.