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Alzheimer’s disease (AD) is a progressive, neurodegenerative brain disorder associated with loss of memory and cognitive function. Beta-amyloid (Aβ) aggregates, in particular, are known to be highly neurotoxic and lead to neurodegeneration. Therefore, blockade or reduction of Aβ aggregation is a promising therapeutic approach in AD. We have previously reported an inhibitory effect of the methanol extract of Perilla frutescens (L.) Britton (Lamiaceae) and its hexane fraction on Aβ aggregation. Here, the hexane fraction of P. frutescens was subjected to diverse column chromatography based on activity-guided isolation methodology. This approach identified five asarone derivatives including 2,3-dimethoxy-5-(1E)-1-propen-1-yl-phenol (1), β-asarone (2), 3-(2,4,5-trimethoxyphenyl)-(2E)-2-propen-1-ol (3), asaronealdehyde (4), and α-asarone (5). All five asarone derivatives efficiently reduced the aggregation of Aβ and disaggregated preformed Aβ aggregates in a dose-dependent manner as determined by a Thioflavin T (ThT) fluorescence assay. Furthermore, asarone derivatives protected PC12 cells from Aβ aggregate-induced toxicity by reducing the aggregation of Aβ, and significantly reduced NO production from LPS-stimulated BV2 microglial cells. Taken together, these results suggest that asarone derivatives derived from P. frutescens are neuroprotective and have the prophylactic and therapeutic potential in AD.

The arial parts of Scutellaria barbata D. Don (Lamiaceae) efficiently inhibited NO production in BV2 microglial cells, and the active constituents were further isolated based on activity-guided isolation using silica-gel column chromatography, RP-C18 MPLC and prep-HPLC. As the results, 2 flavonoids including 6-methoxynaringenin (1) and 6-O-methylscutellarein (5), and 6 neo-clerodane diterpenes such as scutebarbatine W (2), scutebatas B (3), scutebarbatine B (4), scutebarbatine A (6), 6-O-nicotinolylscutebarbatine G (7), and scutebarbatine X (8) were isolated. The structures of these compounds were elucidated based on NMR and MS data, and the comparison of literature values. All the compounds except compound 7 inhibited NO production efficiently with IC values of lower than 50 μm. Particularly, compounds 1 and 8 were the most efficient with IC values of 25.8 and 27.4 μm, respectively. This is the first report suggesting the potential of S. barbata on the reduction of neuroinflammation.

Beta‐amyloid (Aβ) aggregates are a major cause of Alzheimer's disease (AD), and the inhibition of Aβ aggregation is a good therapeutic target against AD. Thus, the effects of Perilla extract (4–100 µg/mL) on the aggregation of Aβ (20 µM) monomers and disaggregation of pre‐aggregated Aβ aggregates were determined. The Perilla methanol extract and its hexane fraction significantly reduced Aβ aggregation determined by a Theoflavin T fluorescence assay (IC50 = 24.5 and 19.8 µg/mL, respectively) and confirmed by Western blot analysis with native gels. The inhibition of Aβ aggregation by hexane fraction of Perilla extract (20 and 100 µg/mL) rescued the PC12 cells from Aβ aggregate‐induced toxicity to the levels of DMSO‐treated control groups. Furthermore, hexane fraction efficiently disaggregated the preformed Aβ aggregates (IC50 = 10.2 µg/mL). Perilla frutescens var. acuta leaves exhibited anti‐amyloidogenic effects against Aβ aggregation and disaggregation. Practical application These results suggest that P. frutescens var. acuta has the potential to be developed as a preventive and therapeutic agent.

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