Anti-Amyloidogenic Effects of Metasequoia glyptostroboides Fruits and Its Active Constituents

Abstract

Alzheimer’s disease (AD) is a serious neurodegenerative brain disease that interferes with daily life. The accumulation of beta-amyloid (Aβ), along with oxidative stress-inducing neurocellular apoptosis, has been considered one of the causes of AD. Thus, the purpose of this study is to find natural products that can reduce Aβ accumulation. The ethanol extract of Metasequoia glyptostroboides Hu & Cheng fruits (Cupressaceae) significantly reduced the aggregation of Aβ into oligomers and fibrils determined by Thioflavin T (ThT) assay. The solvent-partitioned ethyl acetate layer was further separated based on the bioassay-guided isolation method combined with the ThT assay. As a result, five compounds were isolated and elucidated as taxoquinone (1), sugiol (2), suginal (3), sandaracopimarinol (4), and sandaracopimaradien-19-ol (5) by comparing NMR data with references. All the compounds significantly reduced the aggregation of Aβ and enhanced the disaggregation of pre-formed Aβ aggregates in a dose-dependent manner. Furthermore, the inhibition of Aβ aggregation by the compounds protected PC12 cells from Aβ aggregate-induced toxicity. Among the five compounds, sandaracopimarinol (4) and sandaracopimaradien-19-ol (5) were the most effective. These results suggest that M. glyptostroboides and isolated five compounds have a potential for further study to be developed as anti-AD agents.

Comparative transcriptomic and hormonal analyses reveal potential regulation networks of adventitious root formation in Metasequoia glyptostroboides Hu et Cheng

“…M. glyptostroboides has remained genetically unchanged for millions of years and survived extreme ecological and climatic changes since the Cretaceous period [40]. Extracts from M. glyptostroboides displayed numerous biological and pharmacological activities, including antioxidant, antidermatophytic [41], antifungal [42], anticancer [43], and anti-amyloidogenic [44]. Due to the limited distribution and declining number of native individual trees found in natural stands, M. glyptostroboides was listed as a Class I rare and endangered species in the List of Chinese Rare and Endangered Plants about 30 years ago [45].…”