Syzygium aromaticum (L.) Merr. & L.M.Perry mitigates iron-mediated oxidative brain injury via in vitro, ex vivo, and in silico approaches

Abstract

Clove (Syzygium aromaticum) has been identified as a spice high in phytochemicals that could be exploited in drug development. The purpose of this study is to investigate the neuroprotective effect of S. aromaticum on Fe2+-mediated oxidative brain damage via in vitro, ex vivo, and in silico studies. We assessed the in vitro antioxidant activities of aqueous S. aromaticum (ASAE) using standard procedures. Oxidative damage was induced in rat brain tissues by incubating them with FeSO4 and treating them with different concentrations of ASAE. Biochemical parameters like CAT, SOD, GSH, MDA, and NO levels, cholinergic and purinergic enzyme activity, glucose-6-phosphatase (G6Pase), and fructose-1,6-bisphosphatase (F-1,6-BPase) were all measured in the brain tissues. Inducing brain tissue damage reduced GSH levels, SOD, CAT, and ENTPDase activity while increasing MDA and NO levels, ATPase, G6Pase, and F-1,6-BPase activity (p < .05). These levels and activities returned to near-normal levels after ASAE treatment (p < .05). In a molecular docking investigation, the two leading phytochemicals for AChE were ellagic acid and stigmasterol, with ellagic acid having a greater binding affinity for the BChE enzyme. Stigmasterol also had more binding energy than the BACE-1 protein. In addition, cholesterol had the highest binding energy to MAO-B and BACE-1. Rhamnetin exhibited strong binding to both BChE and the Na+/K+ ATPase. The analysis of the trajectories of led phytochemicals complexed to respective proteins in comparison with the unbound proteins revealed high degree of stability in 100 ns molecular dynamics. These data imply that ASAE can protect against oxidative brain damage by preventing oxidative stress, modifying cholinergic and purinergic activity, and controlling gluconeogenesis.