Cultivation Factors That Affect Amyloid-β Aggregation Inhibitory Activity in Perilla frutescens var. crispa

Alzheimer's disease (AD) is thought to be caused by the deposition of amyloid-β (Aβ) in the brain. Aβ begins to aggregate approximately 20 years before the expression of its symptoms. Previously, we developed a microliter-scale high-throughput screening (MSHTS) system for inhibitors against Aβ aggregation using quantum dot nanoprobes. Using this system, we also found that plants in the Lamiaceae, particularly Perilla frutescens var. crispa, have high activity. The cultivation environment has the potential to enhance Aβ aggregation inhibitory activity in plants by changing their metabolism. Here, we report on cultivation factors that affected the activity of P. frutescens var. crispa cultivated in three fields under different cultivation conditions. The results revealed that the activity of P. frutescens var. crispa harvested just before flowering was highest. Interestingly, the activity of wind-shielded plants that were cultivated to prevent exposure to wind, was reduced to 1/5th of plants just before flowering. Furthermore, activity just before flowering increased following appropriate nitrogen fertilization and at least one week of drying from the day before harvest. In addition, we confirmed that the P. frutescens var. crispa leaf extracts suppressed Aβ-induced toxicity in nerve growth factor-differentiated PC12 cells. In this study, we demonstrated that flowering, wind, soil water content, and soil nitrogen content affected Aβ aggregation inhibitory activity, necessary to suppress Aβ neurotoxicity, in P. frutescens var. crispa extracts. This study provides practical cultivation methods for P. frutescens var. crispa with high Aβ aggregation inhibitory activity for the prevention of AD.