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Seco-Prenylated Butylphloroglucinol Derivatives from Hypericum elodeoides and Their Anti-Alzheimer's Disease
Wenjing Tian1, Shoulun He1, Shengfei Zhong1
1Fujian Provincial Key Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361005, China.
Abstract:
Hyperelodeoines A and B (1 and 2, respectively), two unprecedented seco-prenylated butylphloroglucinol derivatives, along with two known analogues (3 and 4), were identified from Hypericum elodeoides. Compounds 1 and 2, featuring a 7/5 fused ring core, represent the first examples of phloroglucinol ring-opening products derived from the [3.2.1]-type bicyclic polyprenylated acylphloroglucinols (BPAPs). Notably, 2 and 4 significantly upregulated ABCA1 and ApoE protein levels in BV-2 cells. Dual-luciferase reporter assay, CETSA, and SPR analysis identified PPARγ as the potential target of 2 and 4. In vivo zebrafish studies further demonstrated that 2 and 4 exhibited remarkable anti-Alzheimer's disease (AD) effects with no detectable toxicity or teratogenicity. Thus, 2 and 4 could activate PPARγ and show promise as anti-AD agents.
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