Abstract. In the present study, we aimed to determine the effects of herbs or spices on the expression of presenilin 1, a molecule involved in γ-secretase activity and the generation of amyloid-β peptide in Alzheimer's disease. Western blot analysis revealed that presenilin 1 protein expression was down-regulated by stimulation with turmeric or cinnamon extracts in vitro, while the effects on presenilin 1 gene expression examined by reverse transcriptase-polymerase chain reaction were unaltered. Our results showed that curcumin, a component of turmeric, induced the down-regulation of presenilin 1 protein in Jurkat and K562 cell lines.
IntroductionAlzheimer's disease is a neurodegenerative disease caused by amyloid-β accumulation in brain cells combined with oxidative stress and inflammation (1,2). Neurotoxic amyloid-β is an approximately 4-kDa peptide generated via cleavage of the amyloid-β precursor protein (APP) by the γ-secretase proteolytic complex (3). Presenilin is the catalytic member of the γ-secretase complex, and mutations in presenilin are the major cause of early-onset familial Alzheimer's disease. Presenilin is involved in several biological functions, but is well known for its role in the generation of the amyloid-β peptide in Alzheimer's disease and is therefore thought to be an important drug target for this disorder. Thus, an increased understanding of Presenilin may help to improve the development of drugs for Alzheimer's disease and for other neurological diseases (4).Certain herbs have been demonstrated to possess a multitude of beneficial activities, and herbal medications are currently being used for widespread clinical use in disease therapy, as herbs exhibit relatively mild bioavailability and low toxicity (5). As for Alzheimer's disease, polyphenols extracted from grape seeds have been found to inhibit amyloid-β aggregation, reduce amyloid-β production and protect against amyloid-β neurotoxicity in vitro (6,7). In addition, cryptotanshinone (CTS), an active component of the medicinal herb Salvia miltiorrhiza, has been shown to improve learning and memory in several pharmacological models of Alzheimer's disease (8). Further research demonstrated that CTS improved the cognitive ability and promoted APP metabolism involving the non-amyloidogenic product pathway in rat cortical neuronal cells. Moreover, as the Indian diet is rich in herbs and spices, the incidence of Alzheimer's disease in India is considerably low (9,10). However, the precise molecular mechanisms of the therapeutic effects of medicinal herbs and spices are largely undefined, and limited data and a small body of convincing evidence exist at the molecular level (11). Therefore, basic research and development aimed at elucidating the mechanism of action underlying herbal effects should have high priority. We hypothesized that various herbs or spices may affect the γ-secretase proteolytic function. Therefore, we investigated the in vitro effect of several herbs on the expression of presenilin 1 in cultured human cells.
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