3,4-seco-28-Nor-oleanane triterpenes from Camellia japonica protect from neurotoxicity in a rotenone model of Parkinson’s disease

Abstract

A natural material extract library (Korea Bioactive Natural Material Bank) was screened with respect to their protective effects on neuronal cells, and a 70% ethanol extract from the flowers of Camellia japonica turned out to be a potential hit. Bioassay-guided fractionation of this active extract led to the isolation of six new 3,4-seco-28-nor-oleanane triterpenoids (1e6). The molecular structures of these new triterpenoids were elucidated through extensive spectroscopic analyses, including high-resolution MS and 1Dand 2D-NMR data. In a rotenone model of Parkinson’s disease (PD), compounds 3e6 effectively protected against neurotoxicity in the human dopaminergic SH-SY5Y cell line. Among these 3,4-seco-28-nor-oleanane triterpenoids, 4,17b,29-trihydroxy-16-oxo-3,4-seco-28-norolean-12-en-3-oic acid n-butyl ester (5) exerted the strongest neuroprotective effect by suppressing the expression of a-synuclein and the intracellular production of reactive oxygen species (ROS) induced by rotenone treatment. In addition, compound 5 induced microtubule-associated protein 1A/1B-light chain 3 (LC3), which is known as an autophagy biomarker. These results suggest a new class of chemical entities for developing bioactive compounds for PD therapy.