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• W2088371499 startingPage "2747" @default.
• W2088371499 abstract "Some sesquiterpene lactones were recently demonstrated to inhibit inducible nitric oxide synthase (iNOS)-dependent nitric oxide (NO) synthesis. The primary objective of the present study was, therefore, to find evidence for structural requirements of sesquiterpene lactones regarding their capability to inhibit iNOS-dependent NO synthesis. Sesquiterpene lactones 1-11 were examined for their influence on nitrite accumulation in cell culture supernatants of LPS-induced RAW 264.7 macrophages. Except the taraxinic acid beta-D-glucopyranosylester 8 all compounds showed a dose-dependent inhibition of nitrite accumulation in cell culture supernatants with IC50 values ranging from 0.5 to 36.8 microM. High activity seemed to be dependent on an alpha-methylene-gammalactone functionality. Cytotoxicity and the ability to inhibit activation of transcription factor NF-kappaB are further biological activities of sesquiterpene lactones. The second point of interest was, therefore, whether the structural requirements of sesquiterpene lactones for these activities may differ or be the same for those needed to inhibit iNOS-dependent NO synthesis. Using concentrations of 1-11 required to inhibit NO synthesis cell viability was determined and NF-kappaB binding activity was measured by gel-shift experiments. Interestingly, compounds almost equally effective in inhibiting nitrite accumulation did not show the same cytotoxic potential, and most sesquiterpene lactones inhibited nitrite accumulation at concentrations where inhibition of NF-kappaB activation was not significant. These results suggest that different biological activities of sesquiterpene lactones have different structural requirements." @default.
• W2088371499 created "2016-06-24" @default.
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• W2088371499 date "2000-12-01" @default.
• W2088371499 modified "2023-10-17" @default.
• W2088371499 title "Structural requirements of sesquiterpene lactones to inhibit LPS-induced nitric oxide synthesis in RAW 264.7 macrophages" @default.
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• W2088371499 doi "https://doi.org/10.1016/s0968-0896(00)00202-9" @default.
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