Oxyresveratrol(ORes,trans-2,4,3′,5′-tetrahydroxy stilbene)naturally exists in mulberry,grapes,peanuts and other plants.It belongs to stilbene polyphenolic family and has an extra hydroxyl group at 2-position compari...Oxyresveratrol(ORes,trans-2,4,3′,5′-tetrahydroxy stilbene)naturally exists in mulberry,grapes,peanuts and other plants.It belongs to stilbene polyphenolic family and has an extra hydroxyl group at 2-position comparing with resveratrol(Res).Hence,ORes has stronger antioxidant activity than resveratrol.In present study,we employed a rat hepatic fibrosis model induced by carbon tetrachloride(CCl_(4))and administrated ORes via gavage feeding to study the protective effects and potential mechanisms of ORes against hepatic fibrosis.We demonstrated that rat liver oxidative damage induced by CCl_(4)was significantly alleviated after ORes feeding.Furthermore,the mRNA transcription levels ofα-smooth muscle actinn(˛-SMA),desmin,and two MMPs(MMP2 and MMP9)were reduced and the expression levels of transforming growth factorβ1(TGF-β1),p-small mother against decapen-taplegic protein(Smad)1/2 and p-extracellular signal-regulated kinases(ERK)1/2 in the liver tissue down-regulated dramatically.In a parallel study with Res,ORes showed more efficacious protective effect than Res against rat liver fibrosis,which is attributed to extended conjugation system due to the extra hydroxyl group at 2-position on ORes making it more electron-rich and susceptible to oxidation than Res.Therefore,dietary consumption of mulberry and other fruits containing ORes may be beneficial in the prevention of liver fibrosis.展开更多
There are numerous evaluations of natural products,of which majority are food bioactives,performed up to date for their various health beneficial activities via targeting specific proteins.However,the direct identific...There are numerous evaluations of natural products,of which majority are food bioactives,performed up to date for their various health beneficial activities via targeting specific proteins.However,the direct identification of a targeted protein remains unexplored for natural occurring compounds.Proteolysis targeting chimera(PROTAC)is a type of bifunctional chimeric molecules that can directly degrade the binding proteins targeted by bioactive molecules in an ubiquitin-proteasome pathway.As the agents in protein degradation dependent on ubiquitin ligase,the bifunctional molecule connects the target protein ligand and E3 ligase ligand together via an appropriate linker.It is highly selective and efficient to induce the ubiquitin-mediated degradation of targeted binding proteins.Therefore,it has been demonstrated that the PROTAC technology has broad application in the modulation of the target protein level.In this review,we outlined the advances in PROTAC combined molecule compounds,summarized its quantitative structure-activity relationship,and finally reviewed the methods applied in identifying the target proteins of natural products.We hope it will provide an insightful application of PROTAC techniques in the target protein identification of natural products including food bioactive molecules.展开更多
基金Grant from Hubei Province,China(GRANT number 2019ABA100)。
文摘Oxyresveratrol(ORes,trans-2,4,3′,5′-tetrahydroxy stilbene)naturally exists in mulberry,grapes,peanuts and other plants.It belongs to stilbene polyphenolic family and has an extra hydroxyl group at 2-position comparing with resveratrol(Res).Hence,ORes has stronger antioxidant activity than resveratrol.In present study,we employed a rat hepatic fibrosis model induced by carbon tetrachloride(CCl_(4))and administrated ORes via gavage feeding to study the protective effects and potential mechanisms of ORes against hepatic fibrosis.We demonstrated that rat liver oxidative damage induced by CCl_(4)was significantly alleviated after ORes feeding.Furthermore,the mRNA transcription levels ofα-smooth muscle actinn(˛-SMA),desmin,and two MMPs(MMP2 and MMP9)were reduced and the expression levels of transforming growth factorβ1(TGF-β1),p-small mother against decapen-taplegic protein(Smad)1/2 and p-extracellular signal-regulated kinases(ERK)1/2 in the liver tissue down-regulated dramatically.In a parallel study with Res,ORes showed more efficacious protective effect than Res against rat liver fibrosis,which is attributed to extended conjugation system due to the extra hydroxyl group at 2-position on ORes making it more electron-rich and susceptible to oxidation than Res.Therefore,dietary consumption of mulberry and other fruits containing ORes may be beneficial in the prevention of liver fibrosis.
基金supported by the key scientific research projects of Hunan Provincial Department of Education of China(No.19A513)the National Nonprofit Institute Research Grant of CAFINT,China(No.CAFYBB2018GA001)Grant from Hubei Province,China(GRANT number 2019ABA100)。
文摘There are numerous evaluations of natural products,of which majority are food bioactives,performed up to date for their various health beneficial activities via targeting specific proteins.However,the direct identification of a targeted protein remains unexplored for natural occurring compounds.Proteolysis targeting chimera(PROTAC)is a type of bifunctional chimeric molecules that can directly degrade the binding proteins targeted by bioactive molecules in an ubiquitin-proteasome pathway.As the agents in protein degradation dependent on ubiquitin ligase,the bifunctional molecule connects the target protein ligand and E3 ligase ligand together via an appropriate linker.It is highly selective and efficient to induce the ubiquitin-mediated degradation of targeted binding proteins.Therefore,it has been demonstrated that the PROTAC technology has broad application in the modulation of the target protein level.In this review,we outlined the advances in PROTAC combined molecule compounds,summarized its quantitative structure-activity relationship,and finally reviewed the methods applied in identifying the target proteins of natural products.We hope it will provide an insightful application of PROTAC techniques in the target protein identification of natural products including food bioactive molecules.
