Three new norsesquiterpenoid glycosides, 4'-hydroxyphyllaemblicin B (1) and phyllaemblicins E (2) and F (3), were isolated from the roots of Phyllanthus emblica, together with three known compounds, phyllaemblic acid (4), phyllaemblicin B (5), and phyllaemblicin C (6). Of these, 3 is a new norsesquiterpenoid dimer. The structures of 1-3 were established by spectroscopic data information and by acidic hydrolysis. The isolated compounds, together with two other known analogues, phyllaemblic acid methyl ester (7) and phyllaemblicin A (8), were evaluated for their antiviral activity toward coxsackie virus B3 (CVB3) by an in vitro cytopathic effect inhibitory assay. Compounds 5-7 exhibited strong anti-CVB3 activity.

Amyloid-β (Aβ) and tau are the pathogenic hallmarks in Alzheimer's disease (AD). Aβ oligomers are considered the actual toxic entities, and the toxicity relies on the presence of tau. Recently, Aβ oligomers have been shown to specifically interact with cellular prion protein (PrP C ) where the role of PrP C in AD is still not fully understood. To investigate the downstream mechanism of PrP C and Aβ oligomer interaction and their possible relationships to tau, we examined tau expression in human neuroblastoma BE(2)-C cells transfected with murine PrP C and studied the effect under Aβ oligomer treatment. By Western blotting, we found that PrP C overexpression down-regulated tau protein and Aβ oligomer binding alleviated the tau reduction induced by wild type but not M128V PrP C , the high AD risk polymorphic allele in human prion gene. PrP C lacking the Aβ oligomer binding site was incapable of rescuing the level of tau reduction. Quantitative RT-PCR showed the PrP C effect was attributed to tau reduction at the transcription level. Treatment with Fyn pathway inhibitors, Fyn kinase inhibitor PP2 and MEK inhibitor U0126, reversed the PrP C -induced tau reduction and Aβ oligomer treatment modulated Fyn kinase activity. The results suggested Fyn pathway regulated Aβ−PrP C −tau signaling. Overall, our results demonstrated that PrP C down-regulated tau via the Fyn pathway and the effect can be regulated by Aβ oligomers. Our study facilitated the understanding of molecular mechanisms among PrP C , tau, and Aβ oligomers.