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DOI: 10.1055/a-0770-0994
Synthesis and In Vitro Anti-inflammatory Activity of C20 Epimeric Ocotillol-Type Triterpenes and Protopanaxadiol
Publikationsverlauf
received 29. August 2018
revised 17. Oktober 2018
accepted 23. Oktober 2018
Publikationsdatum:
31. Oktober 2018 (online)
![](https://www.thieme-connect.de/media/plantamedica/201904/lookinside/thumbnails/10-1055-a-0770-0994_pmc0673-1.jpg)
Abstract
Ginseng is a perennial herb that contains various medicinal substances. The major active constituents of ginseng are ginsenosides, which have multifarious biological activities. Some pharmacological activities are closely dependent on the stereoisomers derived from the configuration at C20. In this study, the in vitro anti-inflammatory activity of C20 epimeric ocotillol-type triterpenes (2, 3, 9, and 10) and protopanaxadiol [20(S/R)-protopanaxadiol] were investigated. Epimers 2 and 3 were prepared starting from 20(S)-protopanaxadiol. Epimers 9 and 10 were synthesized from 20(R)-3-acetylprotopanaxadiol (7). The anti-inflammatory activity of 2, 3, 9, 10, 20(S)-protopanaxadiol, and 20(R)-protopanaxadiol was evaluated in cultured mouse macrophage RAW 264.7 cells. The MTT assay was used to measure the cytotoxicity. RAW 264.7 cells were stimulated by lipopolysaccharide to release the inflammatory mediators nitric oxide, prostaglandin E2, TNF-α, and interleukin-6 and anti-inflammatory mediator interleukin-10. The effect of the compounds on the overproduction of nitric oxide, prostaglandin E2, TNF-α, interleukin-6, and interleukin-10 was determined using Griess and ELISA methods. The results demonstrated that the in vitro anti-inflammatory activities of C20 epimeric ocotillol-type triterpenes and protopanaxadiol were different. Both the 20S-epimers (2 and 3) and 20R-epimers (9 and 10) inhibited the release of inflammatory mediator nitric oxide, while mainly the 20S-epimers inhibited the release of inflammatory mediator prostaglandin E2, and the 20R-epimers inhibited the release of inflammatory cytokine TNF-α. Both the 20S-epimers [2, 3, and 20(S)-protopanaxadiol] and 20R-epimers [9, 10, and 20(R)-protopanaxadiol] inhibited the release of inflammatory cytokine interleukin-6, but mainly the 20S-epimers [2, 3, and 20(S)-protopanaxadiol] increased the release of anti-inflammatory mediator interleukin-10.
Key words
Panax sp. - Araliaceae - ocotillol-type triterpenes - protopanaxadiol - epimer - synthesis - anti-inflammatory activity* These two authors contributed equally to this work.
Supporting Information
- Supporting Information
1H NMR, 13C NMR, and HRMS of 4, 5, 6, 9, and 10 are available as Supporting Information.
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