New Monoterpenoid Indole Alkaloids from Tabernaemontana crassa Inhibit β-Amyloid42 Production and Phospho-Tau (Thr217)

来自 Tabernaemontana crassa 的新型单萜吲哚生物碱可抑制 β-淀粉样蛋白 42 的产生和磷酸化 Tau (Thr217)

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作者:Sheng Li, Ling-Ling Han, Ke-Pu Huang, Ye-Han Ma, Ling-Li Guo, Yarong Guo, Xiaoqian Ran, Yong-Gang Yao, Xiao-Jiang Hao, Rongcan Luo, Yu Zhang

Abstract

Eleven monoterpenoid indole alkaloids, including three new ones, tabercrassines A-C (1-3), were isolated from the seeds of Tabernaemontana crassa. Tabercrassine A (1) is an ibogan-ibogan-type bisindole alkaloid which is formed by the polymerization of two classic ibogan-type monomers through a C3 unit aliphatic chain. Their structures were established by extensive analysis of HRESIMS, NMR, and ECD spectra. Cellular assays showed that alkaloids 1-3 all reduce Aβ42 production and inhibit phospho-tau (Thr217), a new biomarker of Alzheimer's disease [AD] associated with BACE1-, NCSTN-, GSK3β-, and CDK5-mediated pathways, suggesting these alkaloids' potential against AD.

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