Dihydrosamidin: the basic khellactone ester derived from <i>Phlojodicarpus komarovii</i> and its impact on neurotrophic factors, energy and antioxidant metabolism after rat cerebral ischemia–reperfusion injury

Dihydrosamidin (DHS), a khellactone 3'-<i>O</i>-isovaleroyl-4'-<i>O</i>-acetyl ester, is naturally found in Apiaceae plants yet remains underexplored in biomedical research. Employing HPLC-PDA-MS analysis, the profiling of coumarins in <i>Phlojodicarpus komarovii</i> revealed its significant presence, reaching DHS concentrations of 95 mg/g. DHS administering at a dosage of 80 mg/kg during bilateral transient occlusion of the common carotid artery in Wistar rats prevented neuronal death and decreased neuron-specific enolase levels in the blood serum, increases neurotrophic factors and vascular endothelial growth factor A levels in brain lysate. DHS influenced energy metabolism by reducing the lactate, enhancing the activity of pyruvate kinase and increasing the activities of NADH dehydrogenase and succinate dehydrogenase in brain cells. DHS reduced levels of malondialdehyde and increased activities of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, along with increased levels of reduced glutathione in brain homogenate. Thus, DHS administration promotes neuroplasticity, modulates glycolysis and oxidative phosphorylation and enhances antioxidant defences.