Phytochemical analysis and neuroprotective potential of Achillea santolina L. fractions

Phytochemical characterization, and biological assessment of the neuroprotective activities of Achillea santolina L. methanolic extract (AS), its methylene chloride fraction (MF), butanol fraction (BF) and their isolated compounds were investigated. Twenty-two compounds were identified and quantified in AS using HPLC. Luteolin and kaempferol were isolated from MF. Isovitexin and kaempferol 3-O-glucoside were isolated from BF. The anti-inflammatory activity of the isolated compounds was determined by employing cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitory assays. Neuroprotective activities of AS, MF and BF were investigated against monosodium glutamate (MSG) induced neurotoxicity in rats. Brain damage amended significantly as indicated by the decreased lactate dehydrogenase and tumor necrosis factor. Brain oxidative status was restored as indicated by increased glutathione and decreased lipid peroxidation. AS, MF and BF markedly attenuated histopathological alterations in cerebral cortex and downregulated expression of COX-2, IL-1B, IL-10 genes. The affinity of the isolated compounds for Human Heme Oxygenase-1, 5-LOX, Kelch-like ECH-associated protein and COX-2 was studied. Molecular dynamics simulation and ADME study proved that isovitexin has stable conformations and binding patterns with the active sites of the studied enzymes. For the first time, the neuroprotective potential of AS, fractions and isolated compounds was determined supported by anti-inflammatory study.