Prunella vulgaris L. ve Etkili Bileşiklerinin Alzheimer Hastalığında Nöroprotektif Etkilerinin in vitro Yöntemlerle Araştırılması

Abstract

Alzheimer's disease (AD) manifests as a progressive cognitive disorder, precipitated by the accumulation of soluble amyloid species into insoluble amyloid plaques. This aggregation increases oxidative stress, leading to neuroinflammation in neuronal cells and functional disturbances at cholinergic synapses. Current therapeutic measures for AD are confined to a limited number of drugs offering only symptomatic relief, thus highlighting the importance of discovering new drug molecules. Given that the most effective drugs for AD are of plant origin, plants are considered significant resources in the search for new drug molecules. Considering that the most effective drugs used for AH are of plant origin, plants are thought to be an important source in the search for new drug molecules. Based on this, the role of Prunella vulgaris L., a plant containing numerous phenolic acids that has been widely used in our country, especially internally as an anti-inflammatory agent as a folk medicine, and additionally, has been the subject of some studies due to its antioxidant and anti-inflammatory properties, in the treatment of AH has been investigated using in vitro methods. H2O2-induced neurotoxicity model in SH-SY5Y (human neuroblastoma) cells were used to determine the potential neuroprotective effects of the aqueous ethanolic extract and isolated pure compounds on AD. For this purpose, a total of 5 compounds were isolated from the aerial parts of P. vulgaris using various chromatographic methods from an 80% ethanolic extract. These compounds were elucidated as rosmarinic acid (P-1), ursolic acid (P-2), kaempherol-3-O-rutinoside (P-3), quercetin 3-O-glucoside (P-4), and rutin (P-5) by means of NMR and mass spectrometry techniques. It was determined that the viability of cells treated with H2O2 (500 μM) decreased to 40%. Rosmarinic acid, ursolic acid, and rutin at a concentration of 10 μM each were found to alleviate this cell damage induced by H2O2, increasing cell viability to 54%, 63%, and 73%, respectively. When the extract was used, it was observed that cell viability reached 92% at a concentration of 50 μg/ml. In addition, the inhibitory effects of the extract and pure compounds on acetylcholinesterase and butyrylcholinesterase enzymes were investigated. When the inhibition of butyrylcholinesterase enzyme was examined, the concentrations (IC50) of rosmarinic acid and ursolic acid inhibiting 50% of the enzyme were found to be 15.65 and 42.68 µM, respectively. The results obtained are important in terms of contributing to the literature with evidence supporting the traditional use of Prunella species and their neuroprotective effects.