Affiliations: [a] Tsinghua University School of Medicine, Haidian District, Beijing, China | [b] Key Laboratory of Tea Biochemistry and Biotechnology of Ministry of Education and Ministry of Agriculture, Anhui Agricultural University, Hefei, China
Correspondence:
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Correspondence to: Rui-tian Liu, Tsinghua University School of Medicine, Haidian District, Beijing 100084, China. Tel.: +86 010 62797102; Fax: +86 010 62792995; E-mail: [email protected].
Note: [1] These authors contributed equally to the work.
Abstract: Amyloid-β (Aβ) plays a pivotal role in Alzheimer's disease (AD) pathogenesis and in toxic mechanisms such as oxidative stress, mitochondrial dysfunction, calcium turbulence, and apoptosis induction. Therefore, interfering with Aβ aggregation has long been one of the most promising strategies for AD treatment. Ecdysterones (ECRs) are steroidal hormones in insects and terrestrial plants that have high structural diversity and multiple beneficial pharmacological activities. Here, we studied the effects of six ECRs on Aβ aggregation and cytotoxicity. Two ECRs with an acetoxyl group at the 2 or 3 position and saturated chains as side groups showed apparent promotion of Aβ42 fibrilization, resulting in less Aβ42 oligomers in the samples. Another three with unsaturated side chains clearly inhibited Aβ aggregation and disaggregated preformed fibrils, but increased the Aβ42 oligomer levels. Nevertheless, our MTT results showed that all ECRs tested inhibited Aβ42-induced cytotoxicity. This protective activity may be partly attributable to ECR-mediated amelioration of Aβ42-induced release of reactive oxygen species. Taken together, our findings suggest that ECRs, a series of natural compounds in many plants and insects, have therapeutic potential in AD and that the deduced structure-activity relationships may be beneficial in drug design for the treatment of AD and other amyloidoses.
