Amyloid-β aggregation inhibitors are expected to be therapeutic or prophylactic agents for Alzheimer's disease. Rosmarinic acid, which is one of the main aggregation inhibitors derived from Lamiaceae, was employed as a lead compound and its 25 derivatives were synthesized. In this study, the structure-activity relations of rosmarinic acid derivatives for the amyloid-β aggregation inhibitory effect (MSHTS assay), antioxidant properties, and xanthine oxidase inhibition were evaluated. Among the tested compounds, compounds 16d and 19 were found to the most potent amyloid aggregation inhibitors. The SAR revealed that the necessity of the presence of the phenolic hydroxyl on one side of the molecule as well as the lipophilicity of the entire molecule. The importance of these structural properties was also supported by docking simulations.

Species of the genus Rhododendron have been used in traditional Chinese medicine, with the medicinal herb “Manshanfong” used as an expectorant and for the treatment of acute bronchitis. Daurichromenic acid (DCA), a constituent of Rhododendron dauricum, is a meroterpenoid with antibacterial, anti-HIV, and anti-inflammatory activities. However, the mechanisms underlying these pharmacologic activities are poorly understood. To develop new drugs based on DCA, more information is required regarding its interactions with biomolecules. The present study showed that DCA inhibits the activity of the enzyme sphingomyelin synthase, with an IC₅₀ of 4 µM. The structure–activity relationships between DCA and sphingomyelin synthase were evaluated using derivatives and cyclized hongoquercin A. In addition, DCA was found to inhibit amyloid β aggregation. These results may help in the design of effective drugs based on DCA.

Synthesis of bicyclic compounds was achieved via a lipase-catalyzed, stereoselective, domino Michael–aldol reaction of 2-methyl-1,3-cycloalkanedione and methyl vinyl ketone. Appropriate reaction conditions, including the type of enzyme, solvent, and temperature, were determined. In addition, the effects of solvent polarity and addtives were investigated. The reaction proceeded in the presence of lipase AS in a solution of 20% acetone in dimethylsulfoxide (DMSO) at 10 °C for 8 days, followed by the addition of p-toluenesulfonic acid (TsOH) to afford bicyclic compounds in 51–83% yields with moderate stereoselectivity. Although this domino Michael–aldol reaction showed only moderate stereoselectivity, even with the acid-supported enhancement of the reaction, these results represent potential new applications for lipase.

The aggregation and accumulation of amyloid β (Aβ) in the brain is a trigger of pathogenesis for Alzheimer’s disease. Previously, we developed a microliter-scale high-throughput screening (MSHTS) system for Aβ₄₂ aggregation inhibitors using quantum-dot nanoprobes. The MSHTS system is seldom influenced by contaminants in samples and is able to directly evaluate Aβ₄₂ aggregation inhibitory activity of samples containing various compounds. In this study, to elucidate whether the MSHTS system could be applied to the evaluation of processed foods, we examined Aβ₄₂ aggregation inhibitory activity of salad dressings, including soy sauces. We estimated the 50% effective concentration (EC₅₀) from serial diluted dressings. Interestingly, all 19 commercial dressings tested showed Aβ₄₂ aggregation inhibitory activity. It was suggested that EC₅₀ differed by as much as 100 times between the dressings with the most (0.065 ± 0.020 v/v%) and least (6.737 ± 5.054 v/v%) inhibitory activity. The highest activity sample is traditional Japanese dressing, soy sauce. It is known that soy sauce is roughly classified into a heat-treated variety and a non-heat-treated variety. We demonstrated that non-heat-treated raw soy sauce exhibited higher Aβ₄₂ aggregation inhibitory activity than heat-treated soy sauce. Herein, we propose that MSHTS system can be applied to processed foods.

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.