A new caprolactone derivative, (Z)-7-(16-hydroxyhexadecyl)-3-(propoxycarbonyl)oxepan-4-en-2-one (poecilone A), was isolated from the leaves of Poeciloneuron indicum, an endemic tree of the Western Ghats in India. Poecilone A exhibited dose-dependent inhibition of acetylcholinesterase (AChE) with an IC50 value of 2.23 µM. Fluorescence-based assays demonstrated that poecilone A promotes amyloid beta (Aβ) degradation and inhibits Aβ aggregation. Specifically, neprilysin (NEP) and insulin-degrading enzyme (IDE) cleave qf-Aβ(1-7)C, while NEP and angiotensin-converting enzyme (ACE) target qf-Aβ(12-16)AAC. At concentrations of 5.0 and 7.5 µM, poecilone A increased fluorescence in both peptide cleavage assays, suggesting a potential enhancement of NEP-associated enzymatic activity. These dual activities of AChE inhibition and NEP upregulation highlight poecilone A as a promising natural lead compound for the mitigation of Alzheimer's disease.
Sreekumari et al. (Sat,) studied this question.