The Effect And Mechanism Of Prion Replication Induced By Stilbenes In Vitro

Resveratrol(Res),pterostilbene(Pte)and piceatannol(Pic)are three of common stilbene compounds.It was found that Res could block the prion replication in a scrapie infected cell line SMB-S15 and remove the infectivity of the treated cell lysates in the animal tests.However,it is not clear whether other Stilbene compounds are effective and the possible mechanism of how they work.In this study,we have comparatively evaluated the effectiveness of three stilbene compounds,Res,Pte and Pic,on inhibiting prion propagations in the levels of cell culture,protein misfolding cyclic amplification(PMCA)and real-time quaking induced conversion(RT-QuIC).Using a biomolecular interaction analysis system(Biacore system),the molecular bindings of Res and Pte with recombinant PrPs were also observed.All three chemicals showed active suppressions on PrPSc replication in SMB-S15 cells,in which Res seemed to be the most active one at the same working amount(mole),followed by Pic and Pte.Mouse-derived PMCA tests using cellular prion(from the lysates of SMB-cells)and brain prions(from brain homogenates of scrapie agents S15-,139A-or ME7-infected mice)as the seeds verified that Res,Pte and Pic inhibited the amplifications of PK-resistant signals.Res revealed also the most effective inhibiting activity and followed by Pic.Mouse-derived RT-QuIC using the same seeds demonstrated that those three stilbene compounds efficiently inhibited the fibril formation.However,Pic was the most effective one,followed by Res and Pte.Furthermore,the inhibition activities of Res,Pte and Pic on the brain-derived prion from another species rodent,scrapie agent 263K-infected hamster,were tested with hamster-derived PMCA and RT-QuIC.The inhibiting activities of those chemicals on hamster-derived prion were also detected,in which Pic was the most effective one apparently,followed by Res and then Pte.According to the results of Biacore,Res showed much stronger binding affinities with mouse recombinant PrP and hamster recombinant PrP than Pte,while both chemicals revealed stronger markedly binding affinities with mouse recombinant PrP than hamster recombinant PrP.Our data here indicate that stilbene compounds have the ability to block PrPSc replication in vitro with different species prions.The suppressive effects of stilbene compounds are likely associated with their molecular binding activities with PrPs.