Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pat...Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside.展开更多
Chicoric acid(CA),a natural phenolic acid,has been used as a nutraceutical food ingredient due to its powerful antioxidant,anti-HIV and anti-diabetic bioactivities.CA could be partly metabolized into caffeic acid(CFA)...Chicoric acid(CA),a natural phenolic acid,has been used as a nutraceutical food ingredient due to its powerful antioxidant,anti-HIV and anti-diabetic bioactivities.CA could be partly metabolized into caffeic acid(CFA)and caftaric acid(CTA)on cytochrome P450s in rat liver microsomes.To compare the protective effects of CA and its metabolites on biomolecules and inflammatory responses,oxidative damage induced by free radicals in vitro and microglial inflammation triggered by lipopolysaccharide in BV2 cells were constructed.Results showed that CA,CTA and CFA all significantly inhibited protein degradation and carbonylation induced by hydroxyl radicals and alcoxyl radicals,and suppressed hemin/nitrite/H2O2 triggered-nitration.Moreover,CA,CTA and CFA all exerted remarkable inhibition capacities on linoleic acid and soybean lecithin liposomes peroxidation in a dose-dependent manner,and restrained the oxidation of herring sperm DNA,as well as the breakage of pBR322 plasmid DNA.Furthermore,CA and its metabolites suppressed lipopolysaccharide-induced decline of BV2 cell viability and the production of NO and ROS.However,bioactivities of CA were significantly stronger than those of its metabolites within a certain concentration range.This study provides scientific basis for the application of CA and its metabolites as nutrition and natural antioxidants.展开更多
基金supported by the Open Project Program of the State Key Laboratory of Food Nutrition and Safety,Tianjin University of Science and Technology(No.SKLFNS-KF-202201)the Open Project of the Key Laboratory of Environmental Pollution Monitoring and Disease Control,Ministry of Education,Guizhou Medical University,China(No.GMU-2022-HJZ-06)。
文摘Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside.
基金This work was supported by the National Key Research and Development Program of China(No.2016YFD0400601)the Science and Technology Coordination Project of Innovation in Shaanxi province(NO.2014KTCL02-07).
文摘Chicoric acid(CA),a natural phenolic acid,has been used as a nutraceutical food ingredient due to its powerful antioxidant,anti-HIV and anti-diabetic bioactivities.CA could be partly metabolized into caffeic acid(CFA)and caftaric acid(CTA)on cytochrome P450s in rat liver microsomes.To compare the protective effects of CA and its metabolites on biomolecules and inflammatory responses,oxidative damage induced by free radicals in vitro and microglial inflammation triggered by lipopolysaccharide in BV2 cells were constructed.Results showed that CA,CTA and CFA all significantly inhibited protein degradation and carbonylation induced by hydroxyl radicals and alcoxyl radicals,and suppressed hemin/nitrite/H2O2 triggered-nitration.Moreover,CA,CTA and CFA all exerted remarkable inhibition capacities on linoleic acid and soybean lecithin liposomes peroxidation in a dose-dependent manner,and restrained the oxidation of herring sperm DNA,as well as the breakage of pBR322 plasmid DNA.Furthermore,CA and its metabolites suppressed lipopolysaccharide-induced decline of BV2 cell viability and the production of NO and ROS.However,bioactivities of CA were significantly stronger than those of its metabolites within a certain concentration range.This study provides scientific basis for the application of CA and its metabolites as nutrition and natural antioxidants.
