Objective To determine the inhibitory effects of 21 resveratrol derivatives and 3 natural curcuminoids on lipopolysaccharide(LPS)-induced Nitric oxide(NO)and tumor necrosis factor-alpha(TNF-α)production in microglia ...Objective To determine the inhibitory effects of 21 resveratrol derivatives and 3 natural curcuminoids on lipopolysaccharide(LPS)-induced Nitric oxide(NO)and tumor necrosis factor-alpha(TNF-α)production in microglia and their structure-activity relationships.Methods Cell viability was evaluated by the MTT reduction assay.Accumulation of nitrite(NO2-)in culture supernatant fluids was measured by the Griess reaction.Sodium nitroprusside(SNP)(2.5 mM)solution was used to determine the scavenging activities of these compounds.The levels of TNF-α in the culture medium were measured by using an ELISA kit.Semi-quantitative RT-PCR analysis was used to determine the mRNA levels of inducible NOS(iNOS)and TNF-α.Results It was found,for the first time,that certain resveratrol derivatives that have 3,5-dimethoxyl groups in the A-ring,such as(E)-4-(3,5-dimethoxystyryl)phenol(pterostilbene,compound 2),or have substituted the B-ring of resveratrol with quinolyl,such as(E)-5-[2-(quinolin-4-yl)vinyl]benzene-1,3-diol(compound 18)and(E)-4-(3,5-dimethoxystyryl)quinoline(compound 19),strongly inhibited NO production.Compounds 2,18,and 19 reduced LPS-induced protein and mRNA expression of inducible NO synthase(iNOS),but did not display direct NO-scavenging activity up to 30 μM in sodium nitroprusside(SNP)solution.Moreover,compounds 2,18,and 19 could also significantly inhibit the production of TNF-α by LPS-activated microglia.Furthermore,we found the demethoxy derivatives of curcumin have more potent inhibition activity on NO and TNF-α releasing in activated-microglia.Conclusions In the present study we compared the activated-microglia inhibition effect of resvertrol,curcumin and their derivatives and provided a glance of the structure-activity relationships of these compounds,the information is beneficial to design new potent compounds which can provide better therapeutic implications for various neurodegenerative diseases.展开更多
Curcumin(N1),demethoxycurcumin(N2) and bisdemethoxycurcumin(N3) were isolated from the extract of Curcuma longa(turmeric),and curcumin derivatives(N11～N14) were synthesized.Curcuminoids and curcumin derivatives were ...Curcumin(N1),demethoxycurcumin(N2) and bisdemethoxycurcumin(N3) were isolated from the extract of Curcuma longa(turmeric),and curcumin derivatives(N11～N14) were synthesized.Curcuminoids and curcumin derivatives were evaluated in vitro for the aldose reductase inhibitory activity.The results showed that curcuminoids and curcumin derivatives with hydroxyl or carboxyl acid groups exerted inhibitory activities on aldose reductase,and curcuminoid(N1) and curcumin derivative compound(N13) exhibited potential inhibitory activities.展开更多
文摘Objective To determine the inhibitory effects of 21 resveratrol derivatives and 3 natural curcuminoids on lipopolysaccharide(LPS)-induced Nitric oxide(NO)and tumor necrosis factor-alpha(TNF-α)production in microglia and their structure-activity relationships.Methods Cell viability was evaluated by the MTT reduction assay.Accumulation of nitrite(NO2-)in culture supernatant fluids was measured by the Griess reaction.Sodium nitroprusside(SNP)(2.5 mM)solution was used to determine the scavenging activities of these compounds.The levels of TNF-α in the culture medium were measured by using an ELISA kit.Semi-quantitative RT-PCR analysis was used to determine the mRNA levels of inducible NOS(iNOS)and TNF-α.Results It was found,for the first time,that certain resveratrol derivatives that have 3,5-dimethoxyl groups in the A-ring,such as(E)-4-(3,5-dimethoxystyryl)phenol(pterostilbene,compound 2),or have substituted the B-ring of resveratrol with quinolyl,such as(E)-5-[2-(quinolin-4-yl)vinyl]benzene-1,3-diol(compound 18)and(E)-4-(3,5-dimethoxystyryl)quinoline(compound 19),strongly inhibited NO production.Compounds 2,18,and 19 reduced LPS-induced protein and mRNA expression of inducible NO synthase(iNOS),but did not display direct NO-scavenging activity up to 30 μM in sodium nitroprusside(SNP)solution.Moreover,compounds 2,18,and 19 could also significantly inhibit the production of TNF-α by LPS-activated microglia.Furthermore,we found the demethoxy derivatives of curcumin have more potent inhibition activity on NO and TNF-α releasing in activated-microglia.Conclusions In the present study we compared the activated-microglia inhibition effect of resvertrol,curcumin and their derivatives and provided a glance of the structure-activity relationships of these compounds,the information is beneficial to design new potent compounds which can provide better therapeutic implications for various neurodegenerative diseases.
文摘Curcumin(N1),demethoxycurcumin(N2) and bisdemethoxycurcumin(N3) were isolated from the extract of Curcuma longa(turmeric),and curcumin derivatives(N11～N14) were synthesized.Curcuminoids and curcumin derivatives were evaluated in vitro for the aldose reductase inhibitory activity.The results showed that curcuminoids and curcumin derivatives with hydroxyl or carboxyl acid groups exerted inhibitory activities on aldose reductase,and curcuminoid(N1) and curcumin derivative compound(N13) exhibited potential inhibitory activities.
